Fight Aging!

The Methuselah Foundation volunteers have released a couple of fine-looking PDF format brochures. One outlines the initiatives and mission of the Foundation, while the second introduces the recently announced NewOrgan Prize. They should be put to good use at conventions, for friends, and as handouts - so get to it!

From the first brochure:

Aging is inevitable. Or is it? Alzheimer's, cancer, stroke and heart attack are among the familiar and dreaded results of aging. Knowing - but not wanting to accept - that fate we looked deeper to explore how and why our bodies age. We found that some of our questions had no answers even though scientists believe there is great untapped potential for understanding, reversing and solving the ravages of age. While we dreamed about the possibility of long, healthy lives for ourselves and our children, we realized something had to be done to fully explore the prospects for extending healthy human life.

Methuselah Foundation was founded to do just that. We exist because we believe everyone should enjoy a vibrant and productive life, not just in the early years, but into their 70s, 80s and 90s. Our exploration showed that scientists are interested and eager to understand aging, find solutions and share them. What was lacking were the funds and incentive to make it possible. That is why Methuselah Foundation invests in great scientific research and awards performance based prizes.

An attendee at the Humanity+ UK 2010 conference offers thoughts on transhumanist goals: "The convergence of current technologies such as nanotechnology, biotechnology, information technology and cognitive science (NBIC) and future technologies such as artificial intelligence, mind uploading, cryonics, and simulated reality, is truly inspirational. ... I think we all have a vested interest in Aubrey de Grey's idea that aging is simply a disease, and a curable one at that. His plan is to identify all the components that cause human tissue to age, and design remedies for each of them through his approach called SENS (Strategies for Engineered Negligible Senescence). Once we can extend human life spans by thirty years, we're well on our way to immortality. Aubrey de Grey claims that the first human being to live a thousand years has probably already been born. From the way he talks, the biggest challenge in the race against mortality is funding! So I highly encourage those of you with means and an interest to donate to the SENS Foundation. ... Another fascinating speaker was David Pearce, advocating the abolition of suffering throughout the living world. ... He argues that as we develop these technologies, it is both our moral and hedonistic imperative to rid all sentient beings of pain."

Link: http://beforeitsnews.com/news/38084/Transhumanism_and_the_Future_of_the_Human_Race.html

Sequencing our own DNA and cross-referencing the results against the best of present scientific knowledge will soon be cheap and routine. This is an example of the sort of incremental progress in medical technology that is increasing human life expectancy year after year: a little more prevention here, a little better insight into how to cure there. From ScienceDaily: "For the first time, researchers have used a healthy person's complete genome sequence to predict his risk for dozens of diseases and how he will respond to several common medications. The risk analysis [also] incorporates more-traditional information such as a patient's age and gender and other clinical measurements. The resulting, easy-to-use, cumulative risk report will likely catapult the use of such data out of the lab and into the waiting room of average physicians within the next decade, say the scientists. ... The $1,000 genome is coming fast. The challenge lies in knowing what to do with all that information. We've focused on establishing priorities that will be most helpful when a patient and a physician are sitting together looking at the computer screen. ... Information like this will enable doctors to deliver personalized health care like never before. Patients at risk for certain diseases will be able to receive closer monitoring and more frequent testing, while those who are at lower risk will be spared unnecessary tests. This will have important economic benefits as well, because it improves the efficiency of medicine."

Link: http://www.sciencedaily.com/releases/2010/04/100429204658.htm

If the immune system is chronically stressed, such as by organ transplants or HIV infection, then it ages noticeably faster - in effect the immune system wears down with overuse like a burdened machine. You might look on this sort of outcome as a much faster burn through the normal process of immune system use and degeneration with age, and it has consequences in terms of health and life expectancy. For example:

Study links liver transplantation to accelerated cellular aging

The University of Cambridge research team investigated whether the chronic immune stress of liver disease and organ transplantation accelerates aging of the immune system, which in turn contributes to excess morbidity and mortality in established liver graft recipients. Study leader Dr. Graeme Alexander explains, "There is a marked increase in the prevalence of cardiac disease, malignancy, cerebrovascular disease and infections in patients with established liver grafts, affecting a majority of cases eventually and which in the past have been attributed to agents used to suppress immune responses. However, an alternative (and not exclusive) hypothesis is that liver transplant recipients develop premature immune senescence which is also associated with these same pathologies, perhaps consequent to chronic [immune system activation]."

Early immune senescence in HIV disease

During aging, a reduction in T-cell renewal, together with a progressive enrichment of terminally differentiated T cells, translates into a general decline of the immune system, gradually leading to immunosenescence. ... Constant stimulation of the immune system by HIV or due to co-infections activates the innate and adaptive immune system, resulting in release of mediators of inflammation. Immune activation coupled with lack of anti-inflammatory responses likely results in accelerated aging in HIV disease.

The accelerated immune system aging experienced by those who suffer HIV infection is well known, and an area of ongoing medical research. It's quite possible that some of the strategies being developed by the AIDS research community to address this issue could be adapted to rejuvenate aspects of a normally age-damaged immune system. You might look to these posts and articles, for example:

• AIDS-Damaged Immune Systems and Aging Immune Systems
• Telomerase to Fix Immune System Aging
• Reprogramming an Exhausted Immune System

Desai S, & Landay A (2010). Early immune senescence in HIV disease. Current HIV/AIDS reports, 7 (1), 4-10 PMID: 20425052

This EurekAlert! release looks at some of the challenges facing the increasing number of research groups who are attempting to destroy cancer stem cells: "Many of the colon cancer cells that form tumors can be killed by genetically short-circuiting the cells' ability to absorb a key nutrient, a new study has found. While the findings are encouraging, the test tube study using human colon cancer cells also illustrates the difficulty of defeating these cells, known as cancer stem cells (CSCs). ... It is becoming more evident that only a small number of cells in the tumor are capable of forming the tumor, namely the cancer stem cell. So the new strategy is to eliminate the cancer stem cells and thus lower the recurrence of cancer. ... Because CSCs have properties similar to normal stem cells, we have to find a way to attack them while keeping the adult stem cells alive. ... To do that, the research team inactivated a receptor that is found in increased amounts in colon cancer cells: the insulin-like growth factor receptor (IGF-1R). The colon cancer CSCs seem to need a fair amount of IGF to live, more than other cells, and they can't function without the IGF receptor. ... Working with human colon cancer cells, the researchers manipulated the cellular genetics using small interfering RNA (siRNA) to prevent the synthesis of IGF-1R. In this way, they reduced the number of IGF receptors by half, and reduced the number of CSCs by 35%."

Link: http://www.eurekalert.org/pub_releases/2010-04/foas-ras042210.php

From TechNewsWorld: "During his homily this Easter, Pope Benedict argued that medical science, in trying to defeat death, is leading humanity toward likely condemnation. It's a position at odds with the value of life, one that the Church will likely revise years from now, replaying the institution's embarrassment over censoring Galileo. ... If scientists are successful in finding techniques to rebuild cartilage, repair organs, and cure cancer, people will indeed be living longer - but they will also be healthier, more energetic and youthful. Health-extension, when it happens, will allow people to live longer, better. Consider that 60-year-olds today are not in the same shape as their counterparts were in the 1800s or 1900s. As humans discovered how to take better care of themselves, through improved nutrition, the use of antibiotics and other techniques, 'chronological age' became less synonymous with 'biological age.' That is, many of today's 60-year-olds act and feel much younger than one might expect. The average human life expectancy today is close to 80 years but in 1850, it was 43 years, and in 1900 it was 48 years. One can imagine someone in 1850 arguing that doubling life expectancy would be terrible, because innovation might be at risk and there would be more old people around. But would anyone today say they are sorry that science made it possible to live longer and healthier lives?"

Link: http://www.technewsworld.com/story/Galileo-20-Here-Comes-Another-Apology-69876.html

Animal experimentation is horrible and terrible. Even in the most ethical of studies suffering is inflicted upon animals that otherwise would not have happened; entire genotypes of animals doomed to additional suffering have been bred in some cases. But the alternative is far worse: to not perform these animal studies, or rather for some privileged group to use force to prevent others from performing such studies, and so bring progress in medicine to a grinding halt. Without animal studies there would be no new meaningful advances in medical science. It is a harsh and unpleasant aspect of the human condition that forcing suffering upon animals in the course of scientific studies is necessary to advance both human and veterinary medicine. A few suffer for the benefit of many - an equation that should make any sane and compassionate person uncomfortable.

Animal studies are even required to refine the science needed to move beyond animal studies. Ethics and morality aside, studies employing animals are expensive and time-consuming. Given the choice, scientists would much rather experiment on cells in a dish, or on slabs of unfeeling cultured tissue, or upon simulations of animals, if these methods would generate results of the same quality. For example:

It’s possible that animal testing, which is required for health and medical products, could be done using tissue generated from stem cells [and] not living creatures. The research by professor Amit Gefen of Tel Aviv University could put lab rats out of work (and harm’s way). His investigation of fat cells, published in Tissue Engineering, suggests that tissue needed for experiments can be produced using fat, skin, bone and muscle cells. Gefen uses adult rat stem cells to create the tissues he needs for his own work on the mechanical properties of pressure ulcers.

In comparison to what might be and what is possible, we live in a barbaric age of suffering, war, death, and sundry other horrors that we like to keep behind the curtains and out of the mind's eye. But barbaric as it is, this age is far better than the past by all such measures. We no longer absolutely, definitely need to slaughter animals for food to sustain the populace, for example, and rates of violence between humans are far lower than in the pre-modern era of tribes and universal poverty. The option stands open today for a society of vegetarians: it is practical from a technological and economic standpoint. That we have not moved rapidly in that direction is our shame, and our descendants will look back on us as savages for this and many other reasons.

Those people who criticize and take action against the use of animals in medical research should first look to their diets, and then to the practice of farming animals. Vast and expansive animal suffering is caused in the name of putting meat into the marketplace - greater many times over each month than in all the animal experiments in modern history. Persuade the omnivores of the human race to relinquish their participation in the meat market before savaging the medical science that will benefit both man and beast.

In short, the human condition is a rotted, cloying swamp, but we're closer to the edge than we were - no longer up to our necks in it, we now have the luxury of finding more of our surroundings to be disgusting and primitive. The way out to solid ground is forward, through more of the same, until our biotechnology becomes good enough to do away with the suffering we must inflict upon animals in order to build better medicine. Perhaps along the way, societies will arise whose members also reject the needless suffering we presently choose to inflict upon animals in order to eat the same diet as our ancestors.

An interesting article: "In what turned out to be his final official engagement as CEO of Sirtris Pharmaceuticals, Christoph Westphal offered some key lessons in how to build a successful biotech company ... It's pretty amazing ... in the last 20 years, we've gone from zero understanding of the genes that play a role in aging to a pretty clear understanding that IGF1 plays a role, MTOR, the Sirtuins play a role, there's 10-15 genes play a role. Many of those are going to be druggable targets. Will Sirtris be successful? I don't know. It's still going to be very risky. But I'll be shocked if there are not drugs in the next 10-15 years that target genes that control aging. ... Westphal did not shirk from addressing the ongoing controversy surrounding the physiological activity of some Sirtris compounds. ... There's a debate in the academic world. We don't know the specific molecular mechanism of why you need a specific substrate on the in vitro screen to find Sirt1 activators. ... It's a numbers game and it's gotten harder with the FDA ... People are spending less on pharma R&D and more on consumer health care and trying to diversify into developing countries and away from Europe and the United States. Fewer drugs are getting approved, revenues are going down, margins are going to go down."

Link: http://www.bio-itworld.com/news/04/26/10/Christoph-Westphal-on-aging-pharmageddon.html

Scientists proceed in their work by discovering a correlation and then picking apart the underlying mechanisms to find out why the correlation exists. In the field of aging research a great many as yet unexplained correlations exist, any one of which may point the way to important new knowledge. Take this for example: "Biological rhythms that oscillate with periods close to 24 h (circadian cycles) are pervasive features of mammalian physiology, facilitating entrainment to the 24 h cycle generated by the rotation of the Earth. In the absence of environmental time cues, circadian rhythms default to their endogenous period called tau, or the free-running period. This sustained circadian rhythmicity in constant conditions has been reported across the animal kingdom, a ubiquity that could imply that innate rhythmicity confers an adaptive advantage. In this study, we found that the deviation of tau from 24 h was inversely related to the lifespan in laboratory mouse strains, and in other rodent and primate species. These findings support the hypothesis that misalignment of endogenous rhythms and 24 h environmental cycles may be associated with a physiological cost that has an effect on longevity."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20392719

A number of researchers are very interested in exploring differences in life span between species as a way to better understand the biology of aging; this is another branch of the mainstream interest in uncovering ways to manipulate genes and metabolism to slow aging. Amongst these scientists is Joao de Magalhaes, who runs the excellent senescence.info websites, including the GenAge and AnAge databases. You should certainly browse through the materials there if you haven't already done so. You might recall that de Magalhaes was also amongst those attempting to raise funds for genetic sequencing of long-lived mammals - again with the aim of learning more about the roots of longevity by way of comparison between species with very different life spans.

There is a good set of data showing a strong correlation between mammalian life span and the composition of mitochondrial DNA - implying that the mitochondrial free radical theory of aging in fact describes the dominant process of degenerative aging in mammals. This fits in with the clear importance of autophagy, as autophagy is the process by which damaged mitochondria are recycled before they can cause more harm to a cell and the surrounding tissue.

Here, however, let me point out a paper by de Magalhaes and other respected names in the field that looks into resistance to inflammation as a possible factor to explain life span differences between species:

Species differences in lifespan have been attributed to cellular survival during various stressors, designated here as 'cell resilience'. In primary fibroblast cultures, cell resilience during exposure to free radicals, hypoglycemia, hyperthermia, and various toxins has shown generally consistent correlations with the species characteristic lifespans of birds and mammals. However, the mechanistic links of cell resilience in fibroblast cultures to different species lifespans are poorly understood.

We propose that certain experimental stressors are relevant to somatic damage in vivo during inflammatory responses of innate immunity, particularly, resistance to ROS, low glucose, and hyperthermia. According to this hypothesis, somatic cell resilience determines species' differences in longevity during repeated infections and traumatic injuries in the natural environment. Infections and injury expose local fibroblasts and other cells to ROS generated by macrophages and to local temperature elevations. Systemically, acute phase immune reactions cause hypoglycemia and hyperthermia. We propose that cell resilience to somatic stressors incurred in inflammation is important in the evolution of longevity and that longer-lived species are specifically more resistant to immune-related stressors.

Inflammation as it applies to aging is also tied in with the degeneration of the immune system. As the immune system suffers damage and misconfiguration over the years, levels of chronic inflammation rise. In effect the immune system becomes more active, with all of the additional stress put upon the body that implies, but provides fewer benefits. This characteristic process is called inflammaging; it is plausible that a species capable of better resisting the consequences of inflammaging, as well as the consequences of inflammation in earlier life, would live longer as a result.

Finch CE, Morgan TE, Longo VD, & de Magalhaes JP (2010). Cell resilience in species lifespans: a link to inflammation? Aging cell PMID: 20415721

Via EurekAlert!: "Adoptive immunotherapy is targeted to situations when the immune system fails to detect a disease [such as cancer]. The adoptive immunotherapy strategy is to harvest T cells from the patient, engineer them to spot the disease and then send them back in, like police detectives with a reliable tip. A major drawback, however, has been that the T cells still need to call for back-up forces from a variety of other cell types in the body, but they can't. They die out quickly without doing enough good. The new approach is to further engineer the T cells to be able to support themselves rather than relying on other immune cells [and] to insert the ability to switch that self-support on or off, to ensure that they don't grow out of control. That way, the T cells can persist in fighting the disease without becoming a cancer themselves. ... This is an integration of a cell-based therapy application with new synthetic biology tools that have come up from foundational research. ... Generally, the results showed that their engineering produced healthier, faster-growing populations of the T cells, until the drugs were withdrawn and growth shut down. In the human cell cultures, for example, the technology led to a 24 percent increase in the live T-cell population compared to controls and 50 percent fewer cells dying off."

Link: http://www.eurekalert.org/pub_releases/2010-04/sumc-ntr042110.php

From MSNBC: "Four common bad habits combined - smoking, drinking too much, inactivity and poor diet - can age you by 12 years, sobering new research suggests. The findings are from a study that tracked nearly 5,000 British adults for 20 years, and they highlight yet another reason to adopt a healthier lifestyle. Overall, 314 people studied had all four unhealthy behaviors. Among them, 91 died during the study, or 29 percent. Among the 387 healthiest people with none of the four habits, only 32 died, or about 8 percent. ... The risky behaviors were: smoking tobacco; downing more than three alcoholic drinks per day for men and more than two daily for women; getting less than two hours of physical activity per week; and eating fruits and vegetables fewer than three times daily. These habits combined substantially increased the risk of death and made people who engaged in them seem 12 years older than people in the healthiest group ... The findings don't mean that everyone who maintains a healthy lifestyle will live longer than those who don't, but it will increase the odds." This study joins many others in putting a number on the harm we do to ourselves by failing to keep up with the health basics.

Link: http://www.msnbc.msn.com/id/36786312/ns/health-aging/

As targeted therapies for cancer have progressed in the labs over the past few years, there have been a handful that stood out from the pack: animal studies in which advanced cancers evaporated rapidly and with few or no side effects. This is what a promising field of medical research looks like once it's underway: a wide range of results that are as good as or somewhat better than existing treatments, and a few that are immensely more beneficial. Researchers gravitate towards what works, and the end result that reaches the clinic is based on the immensely more beneficial approach.

Here is one example of a targeted technology demonstration that uses dendrimers to tie together various components of the therapy. Firstly a popular press piece followed by the published research results:

Scientists make cancer cells vanish

Scottish scientists have made cancer tumours vanish within 10 days by sending DNA to seek and destroy the cells. The system, developed at Strathclyde and Glasgow universities, is being hailed as a breakthrough because it appears to eradicate tumours without causing harmful side-effects. ... In laboratory experiments the Strathclyde research team used a plasma protein called transferrin, which carries iron through the blood, to deliver the therapeutic DNA to the right spot. Once in situ the DNA produced a protein that attacked the tumour cells.

Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA

The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy.

...

The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response).The treatment was well tolerated by the animals, with no apparent signs of toxicity.

This and similar examples are what make me fairly confident that the cancer waiting in my future will be more of a threat to my wallet than my life.

Koppu S, Oh YJ, Edrada-Ebel R, Blatchford DR, Tetley L, Tate RJ, & Dufès C (2010). Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA. Journal of controlled release : official journal of the Controlled Release Society, 143 (2), 215-21 PMID: 19944722

This paper outlines the overlap between the ways in which both processes of aging and eating too much lead to the loss of muscle mass and strength: "Sarcopenia, which is defined by the loss of skeletal muscle mass, predisposes skeletal muscle to metabolic dysfunction which can precipitate metabolic disease. Similarly, overnutrition, which is a major health problem in modern society, also causes metabolic dysfunction in skeletal muscle and predisposition to metabolic disease. It is now the prevailing view that both aging and overnutrition negatively impact skeletal muscle metabolic homeostasis through deleterious effects on the mitochondria. Accordingly, interplay between the molecular pathways implicated in aging and overnutrition that induce mitochondrial dysfunction are apparent. Recent work from our laboratory has uncovered the stress-responsive mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) as a new player in the regulation of metabolic homeostasis in skeletal muscle and mitochondrial dysfunction caused by overnutrition. These observations raise the intriguing possibility that MKP-1 may function as a common target in the convergence between sarcopenia and overnutrition in a pathophysiological pathway that leads to a loss of skeletal muscle mitochondrial function." Going the other way, you might recall that calorie restriction helps to maintain muscle mass with age.

Link: http://www.impactaging.com/papers/v2/n3/full/100135.html

Nature looks at the chaotic state of bringing cancer vaccines to trial: "Many first-generation cancer vaccines such as PANVAC, a pancreatic cancer vaccine, were deemed safe but failed to demonstrate that they significantly slowed the progression of cancer. Because cancer-associated antigens - such as those used in Provenge - are also found at low levels in healthy tissue, their ability to trigger a powerful immune response may be blunted. A second generation of vaccines, designed to provoke a stronger immune response, is under development, with some scientists now focusing on antigens that are found only on tumour cells. ... Over the past decade, researchers have reached a deeper understanding of how tumours actively suppress immune responses in their immediate environment, which can dampen responses to cancer vaccines. To overcome this, some therapies currently in development combine the vaccine with chemotherapies that are designed to counteract this immune suppression. ... For some in the field, the struggle to create effective cancer vaccines conjures up memories of the long battle to develop antibody-based therapies, which are now a mainstay of the biotechnology industry. There, too, a series of clinical-trial failures initially soured the field's reputation ... We realized you just have to test a lot of drugs to find one that works, and it's the same for a cancer vaccine."

Link: http://www.nature.com/news/2010/100421/full/4641110a.html

Cytomegalovirus (CMV) infection is one of the important contributing factors to the decline of the immune system with age. Most people are exposed to this mild persistent herpesvirus over the course of their life; it causes few obvious symptoms, but over time more and more of your immune system resources become uselessly specialized to fight it. An immune cell dedicated to remembering the signature of CMV is unavailable for other uses - and eventually you run out of cells to protect you from new threats, destroy cancers, and clear out senescent cells. This process is one part of the frailty and increased risk of death and disease that comes with old age.

A recent study quantified the risk that comes with a CMV-focused immune system. Mortality rate and incidence of frailty were compared against levels of anti-CMV immune activity, as judged by concentration levels of antibodies:

Cytomegalovirus Infection and the Risk of Mortality and Frailty in Older Women: A Prospective Observational Cohort Study

Present understanding is limited regarding the long-term clinical effect of persistent CMV infection in immunocompetent adults. The authors conducted a prospective observational cohort study (1992-2002) of 635 community-dwelling women in Baltimore, Maryland, aged 70-79 years in the Women's Health and Aging Studies to examine the effect of CMV infection on the risk of frailty, a common geriatric syndrome, and mortality in older women.

The effect of baseline serum CMV antibody (immunoglobulin G) concentration on the risk of 3-year incident frailty, defined by using a 5-component measure, and 5-year mortality was examined with Cox proportional hazards models. Compared with those who were CMV seronegative, women in the highest quartile of CMV antibody concentration had a greater incidence of frailty (hazard ratio = 3.46) and mortality (hazard ratio = 3.81). After adjustment for potential confounders, CMV antibody concentration in the highest quartile independently increased the risk of 5-year mortality (hazard ratio = 2.79).

A CMV fixation should be thought of as yet another form of malfunction or misconfiguration of the immune system, to be put in the same broad category as autoimmune diseases. Some of the research efforts directed towards repairing autoimmune disease may in the future also be turned towards repairing a CMV-specialized immune system. For example, researchers have successfully rebooted the immune system in human patients in recent years: completely destroying and then recreating it in order to remove all immune cells with errant programming. Another possibility is the use of targeted cell killing technologies that can pick out and destroy CMV-specialized immune cells based on their surface markers.

But I know of no groups seriously working towards this end - a frequent refrain here, sad to say. Far greater progress towards extended healthy life could be underway than is presently the case.

Wang GC, Kao WH, Murakami P, Xue QL, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, & Fried LP (2010). Cytomegalovirus Infection and the Risk of Mortality and Frailty in Older Women: A Prospective Observational Cohort Study. American journal of epidemiology PMID: 20400465

More evidence for the benefits of exercise: "Researchers from the University of Washington conducted a six-month clinical trial with 33 participants, 17 of whom were women. All showed early signs of Alzheimer's disease and were between the ages of 55 and 85. The experiment participants underwent a six-month intensive aerobic training program, spending 45 minutes to an hour four times each week on a stationary bicycle or treadmill. At the end of the six months, the participants saw improvement in mental agility, while the control group showed no improvement. Researchers are planning further studies to conduct larger and longer duration trials, following volunteers for years instead of months, for more conclusive data as to whether exercise can prevent full-blown cases of Alzheimer's. ... Other similar studies have been conducted, where researchers have measured the health benefits of resistance training for women between the ages of 65 and 75 who are most at risk for developing Alzheimer's. In one study, after one year of training, women who had completed the training showed better scores on mental acuity and conflict resolution tests than those who didn't."

Link: http://www.cavalierdaily.com/2010/04/21/remember-to-exercise-exercise-to-remember/

Possibly an example of overthinking the issue at the JET, but the section on Finot illustrates that our era does not enjoy a monopoly on rational thinking about extending the healthy human life span: "The beginning of the modern period in the pursuit of radical human enhancement and longevity can be traced to fin-de-siecle/early twentieth-century scientific and technological optimism and therapeutic activism. The works of several authors of the period - Fedorov, Stephens, Bogdanov, Nietzsche and Finot - reveal conflicting ideological and social pathways toward the goals of human enhancement and life extension. Each author represents a particular existing social order, and his vision of human advancement may be seen as a continuation and extension of that order. Therefore, the pursuit of life extension may be considered a fundamentally conservative (or conservationist) enterprise. ... First, these adaptations may question the claims of a particular ideology for supremacy in the promotion of life-extension and life-enhancement. The claims that atheism, capitalism or hedonism are more conducive to the pursuit of longevity, can be countered by historical examples where religion, socialism or asceticism were the foundations. No ideological system seems to have a monopoly, however strongly it asserts that it constitutes the rock-solid ground for this pursuit. It may be that, rather than providing such a foundation, political ideologies enlist the hope for life extension to increase their appeal."

Link: http://jetpress.org/v21/stambler.htm

More genetic and other studies of long-lived people are taking place these days, which means a faster flow of results than has been the case in past years. Part of that can no doubt be attributed to an increased interest in manipulating the aging process in the scientific community, as well as the continually falling cost of the tools needed to run such studies. While perusing PubMed recently, I noticed a few new reports from ongoing longevity studies starting with one from the Leiden Study in the Netherlands, which you might recall produced some interesting results on thyroid hormones and human longevity last year. Here's the paper:

Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study.

Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.

Next, another association between heat shock proteins (HSPs) and longevity. Heat shock proteins are becoming a hot field of study, as is true of all things related to autophagy, the collection of processes by which cells recycle damaged components. The evidence strongly supports more efficient autophagy as a way to live longer in good health - if damaged cellular components aren't hanging around as long, they will cause less lasting harm. For example, boosted autophagy is thought to be one way in which calorie restriction extends life in laboratory animals.

Anti-inflammatory heat shock protein 70 genes are positively associated with human survival

We have studied the association of three single nucleotide polymorphisms [present] in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA and HSPA1B-AA genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers. On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers.

Lastly, an interesting potential association between processing of an important vitamin and human longevity - this sort of study will be repeated for other micronutrients, drugs, and whatever researchers can dream up and justify to funding sources as the cost of performing such work drops.

Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes.

Genetic studies of longevity have focussed on DNA repair, oxidative damage correction and immune-related genes. Vitamin-D works by modulating mineral homeostasis and key physiological processes such as cell proliferation and immune response. Vitamin-D insufficiency has been largely considered a risk factor for life-limiting illnesses including cardiovascular and immune-related diseases and cancer. Vitamin-D acts through vitamin-D-receptor (VDR), which regulates the expression of vitamin-D-response genes. VDR variants have been associated with susceptibility to cancer, bacterial and viral infections, autoimmune diseases, and allergies.

In the present study we evaluated VDR as candidate gene involved in human longevity. We selected five polymorphisms of the VDR gene that capture variability at the 5', coding and 3' regions. Genotype data was obtained from 104 octogenarians (>85 years) and 114 controls (17-40 years). Although differences in genotype and allele distribution did not reach statistical significance, haplotype distribution was distinctive, mainly for 3' region haplotypes and particularly in males. Our results suggest a role for VDR gene variability in aging and longevity.

These three papers are fairly representative of the sort of work presently taking place in the field. There are an unknown but almost certainly large number of small contributory factors making up the genetic component of human longevity, and they are being uncovered at an accelerating pace. What does this all mean for you and I? Probably very little. We will not gain greatly extended longevity through tinkering with our haplotypes - by the time genetic tweaks are happening in the clinic, we will be old. Changes to metabolism that make a year or two's difference in life span across an entire lifetime will be next to worthless to someone already in late life, and already seriously damaged by aging.

We should welcome the advances in practice and understanding of human biology and aging, because all such information will at some point be useful, but we must also recognize that genetic alterations to slow aging are not the path to extending our own lives. We must instead focus on the repair of age-related changes, such as that proposed by the Strategies for Engineered Negligible Senescence.

Rozing MP, Westendorp RG, de Craen AJ, Frölich M, de Goeij MC, Heijmans BT, Beekman M, Wijsman CA, Mooijaart SP, Blauw GJ, Slagboom PE, van Heemst D, & Leiden Longevity Study Group (2010). Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study. Journal of the American Geriatrics Society, 58 (3), 564-9 PMID: 20398121

Singh R, Kølvraa S, Bross P, Christensen K, Bathum L, Gregersen N, Tan Q, & Rattan SI (2010). Anti-inflammatory heat shock protein 70 genes are positively associated with human survival. Current pharmaceutical design, 16 (7), 796-801 PMID: 20388090

Laplana M, Sánchez-de-la-Torre M, Aguiló A, Casado I, Flores M, Sánchez-Pellicer R, & Fibla J (2010). Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes. Biogerontology PMID: 20407924

From the Telegraph, news of continuing incremental progress in understanding the mechanisms of regeneration in lower animals: "research into how Planarian worms can regrow body parts - including a whole head and brain - could one day make it possible to regenerate old or damaged human organs and tissues ... We want to be able to understand how adult stem cells can work collectively in any animal to form and replace damaged or missing organs and tissues. ... Any fundamental advances in understanding from other animals can become relevant to humans surprisingly quickly. If we know what is happening when tissues are regenerated under normal circumstances, we can begin to formulate how to replace damaged and diseased organs, tissues and cells in an organised and safe way following an injury caused by trauma or disease. This would be desirable for treating Alzheimer's disease, for example. With this knowledge we can also assess the consequences of what happens when stem cells go wrong during the normal processes of renewal - for example in the blood cell system where rogue stem cells can result in Leukaemia."

Link: http://www.telegraph.co.uk/science/science-news/7618602/Worms-regeneration-ability-unravelled-by-scientists.html

Life is getting better: "Human society has changed much over the last centuries and this process of 'modernization' has profoundly affected the lives of individuals; currently we live quite different lives from those forefathers lived only five generations ago. There is difference of opinion as to whether we live better now than before and consequently there is also disagreement as to whether we should continue modernizing or rather try to slow the process down. Quality-of-life in a society can be measured by how long and happy its inhabitants live. Using these indicators I assess whether societal modernization has made life better or worse. Firstly I examine findings of present day survey research. I start with a cross-sectional analysis of 143 nations in the years 2000-2008 and find that people live longer and happier in today's most modern societies. Secondly I examine trends in modern nations over the last decade and find that happiness and longevity have increased in most cases. Thirdly I consider the long-term and review findings from historical anthropology, which show that we lived better in the early hunter-gatherer society than in the later agrarian society. Together these data suggest that societal evolution has worked out differently for the quality of human life, first negatively, in the change from a hunter-gatherer existence to agriculture, and next positively, in the more recent transformation from an agrarian to an industrial society. We live now longer and happier than ever before."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848343/

I noticed an interesting idea in the form of a published research paper today. To what degree might we attribute the accelerating rise in human life span in recent centuries to an increased survival rate for people who bear gene variants that (a) harm the prospects for survival to adulthood in low-technology settings, but (b) lead to a longer life expectancy for those who do survive?

Healthy life span is rapidly increasing and human aging seems to be postponed. ... To explain current increase in longevity, I discuss that certain genetic variants such as hyper-active mTOR (mTarget of Rapamycin) may increase survival early in life at the expense of accelerated aging. In other words, robustness and fast aging may be associated and slow-aging individuals died prematurely in the past. Therefore, until recently, mostly fast-aging individuals managed to survive into old age. The progress of civilization (especially 60 years ago) allowed slow-aging individuals to survive until old age, emerging as healthy centenarians now.

This seems worth thinking about for at least a little while: examples of a trade-off between early life robustness and overall longevity abound in the animal kingdom, after all. Calorie restriction is one such example, in fact: an evolved way for individual animals to alter their metabolic settings in response to circumstances so as to focus resources on survival and procreation first and foremost when food is abundant, or on living longer to wait out a period of scarcity. A species that can do this has a considerable advantage over one that cannot.

I can't imagine that testing for signs of the revealed slow aging hypothesis would be straightforward, however. Identified genetic variants of human longevity found via centenarian studies and the like do not appear to have effects anywhere near as large as, say, regular exercise, calorie restriction, or the increase in medical technology and consequent avoidance of chronic disease across the past century. The current consensus is that common genetic differences do not affect life expectancy as greatly as do lifestyle choices. So could a genealogical study coupled with DNA analysis of living descendants be made sufficiently sensitive and statistically reliable to pull out small and changing contributions from different genetic variants over only a few generations? I would think that the best records for this purpose will be recent ones, such as can be found in countries like South Korea, where life expectancy has grown just as rapidly as the wealth of the population over the last 50 years.

With the cost of DNA sequencing falling rapidly, we will no doubt see such studies carried out in the years ahead, and possibly on a very large scale. You might look to the efforts of deCODE in Iceland, for example, as a precursor to this sort of project. It remains an open question as to what might turn up in the data collected - perhaps revealed slow aging, perhaps not.

Blagosklonny MV (2010). Why human lifespan is rapidly increasing: solving "longevity riddle" with "revealed-slow-aging" hypothesis. Aging, 2 (4), 177-82 PMID: 20404395

Spanish scientists "have generated artificial human skin by [tissue] engineering based on agarose-fibrin biomaterial. The artificial skin was grafted onto mice, and optimal development, maturation and functionality results were obtained. This pioneering finding will allow the clinical use of human skin and its use in many laboratory tests on biological tissues - which, additionally, would avoid the use of laboratory animals. Further, this finding could be useful in developing new treatment approaches for dermatological pathologies. ... The skin created in the laboratory showed adequate biocompatibility rates with the recipient and no rejection, dehiscence or infection was registered. ... The experiment [is] the first to create artificial human skin with a dermis made of fibrin-agarose biomaterial. To this date, artificial skin substitutes were elaborated with other biomaterials as collagen, fibrin, polyglycolic acid, chitosan, etc. These biomaterials [added] resistance, firmness and elasticity to the skin. ... Definitively, we have created a more stable skin with similar functionality to normal human skin."

Link: http://www.medicalnewstoday.com/articles/186185.php

A number of studies in recent years have suggested that calorie intake is not the only thing that can alter metabolism to change longevity in lower animals: "Specific odors that represent food or indicate danger are capable of altering an animal's lifespan and physiological profile by activating a small number of highly specialized sensory neurons ... Recent research in model organisms and in humans has shown that sensory experiences can impact a wide range of health-related characteristics including athletic performance, type II diabetes, and aging. Nematode worms and fruit flies that were robbed of their ability to smell or taste, for example, lived substantially longer. However, the specific odors and sensory receptors that control this effect on aging were unknown. Using molecular genetics in combination with behavioral and environmental manipulations, [researchers have identified] carbon dioxide (CO2) as the first well-defined odorant capable of altering physiology and affecting aging. Flies incapable of smelling CO2 live longer than flies with normal olfactory capabilities. They are also resistant to stress and have increased body fat. To many insects, including fruit flies, CO2 represents an ecologically important odor cue that indicates the presence of food (e.g. rotting fruit or animal blood) or neighbors in distress (it has been implicated as a stress pheromone). Indeed, this group of researchers previously showed that merely sensing one's normal food source is capable of reversing the health and longevity benefits that are associated with a low calorie diet. They now establish that CO2 is responsible for this effect."

Link: http://www.eurekalert.org/pub_releases/2010-04/plos-tss041410.php

You might recall that people were enthused a few years back over the work of researcher Zheng Cui, who showed that (a) one breed of lab mice shug off cancer because their immune cells are different in ways that enable them to kill cancer dead, (b) transplanting those immune cells into more vulnerable mice also kills cancer dead, and (c) this same state of affairs exists in humans. Somewhere, someone has an immune system that can kill your cancer. If you could find them and undergo a transplant of leukocyte or granulocyte immune cells, the evidence to date suggests that this would be a very effective therapy.

As put by the folk at Livly, a non-profit startup focused on bringing this form of therapy into the clinic:

Results like this suggest to us that innate immunotherapy is the only approach that has shown the promise to permanently cure advanced cancer. Ironically, it is also one of the most neglected areas in contemporary research.

Which is unfortunately the case. For example, a trial of Cui's work was trumpeted by Wake Forest University back in mid 2008, but never went anywhere, and was withdrawn without enrollment last year. I have no insight into why this happened, but if you look through the Wake Forest clinical trials listings for cancer therapies, you won't see much involving immunotherapy. Read into that what you will.

There is a trial of granulocyte transplants presently running in Florida, however, as I noted last year. Enrollment is by invitation only, which suggests a small organization, limited budget, and consequent slow progress in generating data - but at least someone is giving it a try.

About 75% of US population living today will not die of cancer. It is not uncommon that some people remain cancer-free into their 80s and 90s, even if they are regularly exposed to environmental carcinogens such as air pollutants, cigarette smoking, etc. A frequently asked but unanswered question is why these individuals do not get cancer. There has been a recent report of a colony of cancer-resistant mice developed from a single male mouse that unexpectedly survived challenges of lethal cancer cell injections. In these so-called spontaneous regression/complete resistant (SR/CR) mice, cancer cells are killed by rapid infiltration of leukocytes, mainly of innate immunity. This highly effective natural cancer immunity is inherited and mediated entirely by white blood cells. Moreover, this cancer resistance can be transferred to wild type mice through the transfer of various immune cell types including granulocytes.

This observation raises the possibility that infusion of white blood cells, particularly cells of innate immunity, is a viable anticancer therapy in humans as well.

Another initiative worthy of mention is the Direct Oncology Foundation. These are more folk from the same circles as the Methuselah Foundation, SENS Foundation, and Livly, who are aiming to understand the biochemistry of the cancer-immune mice. Their goal is to enable the development of drug-based therapies to alter immune cells in a patient to have the characteristics of these cancer-killing immune cells, thus eliminating the need for transplants.

In an effort to accelerate the development of a cancer treatment based on innate cancer immunity, the Direct Oncology (DO) Foundation is launching an appeal to raise $100,000 to sequence cancer resistant mice at Wake Forest University. The project is being coordinated by Livly, a Silicon Valley based non-profit corporation dedicated to the development of sustainable cures for the major diseases plaguing humankind. ... The immune systems of the mice successfully fight off different types of advanced cancer. Immune cells from these Spontaneous Regression / Complete Resistance (SR/CR) mice can be used to protect other mice from advanced cancer. Evidence suggests that there is a single place in the SR/CR mouse's genome that confers the remarkable cancer resistance. Ironically, the gene for the cancer resistance has proven inaccessible to standard mouse genetic methods, and its identity and sequence have remained elusive. The progress of clinical efforts was hampered by lack of knowledge of the genetics underlying the cancer resistance.

So far as I know, this is where things stand. I am not aware of other groups seriously investigating this line of research. Not a whole lot of work is taking place, and where progress is happening, it is slow and low-key - a frustrating state of affairs.

The Humanity+ Summit will be held in June at Harvard: "The H+ Summit is part of a larger cultural conversation about what it means to be human and, ultimately, more than human. This issue lies at the heart of the transhumanism movement ... The H+ Summit is a two day event that explores how humanity will be radically changed by technology in the near future. Visionary speakers will explore the potential of technology to modify your body, mind, life, and world. What will it mean to be a human in this next phase of technological development? How can we prepare now for coming changes? We foresee the feasibility of redesigning the human condition and overcoming such constraints as the inevitability of aging, limitations on human and artificial intellects, unchosen psychology, lack of resources, and our confinement to the planet earth. The possibilities are broad and exciting. The H+ Summit will provide a venue to discuss these future scenarios and to hear exciting presentations by the leaders of the ongoing H+ (r)evolution." Amongst the confirmed speakers is biomedical gerontologist and engineered longevity advocate Aubrey de Grey, whose presentations are always well worth attending.

Link: http://hplussummit.com/

Cancer would be far less threatening a condition if metastasis could be reliably blocked: "Like microscopic inchworms, cancer cells slink away from tumors to travel and settle elsewhere in the body. Now, [researchers report] that new anti-cancer agents break down the looping gait these cells use to migrate, stopping them in their tracks. Mice implanted with cancer cells and treated with the small molecule macroketone lived a full life without any cancer spread, compared with control animals, which all died of metastasis. When macroketone was given a week after cancer cells were introduced, it still blocked greater than 80 percent of cancer metastasis in mice. ... macroketone targets an actin cytoskeletal protein known as fascin that is critical to cell movement. In order for a cancer cell to leave a primary tumor, fascin bundles actin filaments together like a thick finger. The front edge of this finger creeps forward and pulls along the rear of the cell. Cells crawl away in the same way that an inchworm moves. Macroketone latches on to individual fascin, preventing the actin fibers from adhering to each other and forming the pushing leading edge."

Link: http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=1117

Here is a popular science level overview of the work of Organovo, a tissue engineering company supported by the Methuselah Foundation, and with a focus on developing the technology needed to make bioprinting a commercial reality. As the article notes, these are early days yet and some years of development lie ahead, but medical technology like bioprinters tends to improve rapidly once it finds its first market application:

Scientists edge closer to printing human tissue

As of right now, the benefit for humans is still years away, perhaps as many as four, said Organovo CEO Keith Murphy. And when and if the company's technology gets certified and hits the market, it will probably have limited application: most likely, the technology could be used at first mainly for crafting very small areas of tissue or new blood vessels. But even those limited applications could mean, for example, that doctors may eventually have the ability to intervene in cases where, for example, a patient has a blocked or damaged blood vessel, and potentially prevent what might otherwise result in a forced amputation. Similarly, someone with damaged nerves could have a gap in a nerve bridged using regenerated cells printed by Organovo's machine.

...

And, Murphy said, the uses for the bioprinting technology are only just being discovered. "With the right funding, we think they can grow this by leaps and bounds...We hope researchers can see if [they can] get to larger and larger pieces of tissue by printing into their architecture...a branch of blood vessels."

...

"I don't think anyone should imagine we'll be printing complete organs in the next year or so," Kraft said. "But like 3D printing, bioprinting" seems like it has the potential for exponential growth. And that means it could just be a short matter of time before medicine and science conquer some of the limits in bioprinting that today seem insurmountable.

Organovo has been in the press a great deal of late, which I think is one of the signs that the broader public understands and supports the goal of building new organs in a way that is still lacking for the goal of engineering greater human longevity. We who advocate funding and progress in longevity science would do well to look behind the scenes and try to better understand why regenerative medicine is such a popular success.

An interesting paper: "The idea that bodies wear out with age is so ancient, so pervasive, and so deeply rooted that it affects our thought in unconscious ways. Undeniably, many aspects of aging, e.g., oxidative damage, somatic mutations, and protein cross-linkage are characterized by increased entropy in biomolecules. However, it has been a scientific consensus for more than a century that there is no physical necessity for such damage. Living systems are defined by their capacity to gather order from their environment, concentrate it, and shed entropy with their waste. Organisms in their growth phase become stronger and more robust; no physical law prohibits this progress from continuing indefinitely. Indeed, some animals and many plants are known to grow indefinitely larger and more fertile through their lives. The same conclusion is underscored by experimental findings that various insults and challenges that directly damage the body or increase the rate of wear and tear have the paradoxical effect of extending life span. Hyperactive mice live longer than controls, and worms with their antioxidant systems impaired live longer than wild type. A fundamental understanding of aging must proceed not from physics but from an evolutionary perspective: The body is being permitted to decay because systems of repair and regeneration that are perfectly adequate to build and rebuild a body of ever-increasing resilience are being held back. Regardless of the reason for this retreat, it should be more fruitful to focus on signaling to effect the ongoing activity of systems of repair and regeneration than to attempt repair of the manifold damage left in the wake of their failure."

Link: http://dx.doi.org/10.1089/rej.2009.0967

Spurring regeneration by use of signalling molecules is a promising field of medical development. Here is an example from the Technology Review: "scientists have identified a pair of peptides that can stimulate new cell growth and improve heart function in rodents induced to have heart attacks. [Researchers are] now testing one of the peptides, periostin, in pigs induced to have heart attacks. Because these animals have hearts similar in size to humans, they provide a good model for testing new therapies prior to human clinical trials. Preliminary results show that injecting the peptide into the pericardium, the lining around the heart, seems to help. ... [This] approach is, to some degree, in competition with stem-cell therapy, which is already being tested in humans. Scientists are working on different ways of harvesting and delivering stem cells to patients with heart disease, and clinical trials have so far yielded mixed results. Transplanted cells appear to have difficulty surviving and integrating into their new environment. In fact, some scientists suggests that benefit of cell transplants comes from the cells ability to stimulate innate growth. Triggering this process with peptides [may] be a simpler method of treatment of certain conditions such as cardiomyopathy [an enlarged heart] where the problem is lack of viable, contractile heart muscle cells."

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=25139

Medical bioremediation is the name given to the SENS Foundation approach to removing one class of harmful waste chemicals that accumulate in our cells with advancing age:

Cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures that are so weird that none of the cell's degradation machinery works on them. This situation is very rare, but in the long run these modified chemicals add up.

Ultimately the chemicals end up in the lysosome, a special vessel that contains the most powerful degradation machinery in the cell. If something can't be broken down there, it just stays there forever. This doesn't matter in cells that divide regularly, because division dilutes the junk enough that it remains at harmlessly low levels, but non-dividing cells gradually fill up with this stuff, making them dysfunctional. The heart, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery wall all suffer from this.

The development of therapies of biomedical remediation breaks down into two distinct lines of research: firstly, to identify naturally occurring bacterial enzymes that digest these unwanted junk chemicals. We know that bacteria containing these enzymes exist because we find no remnants of this chemical junk in graveyards, battlefields, slaughterhouse grounds, and so forth. The SENS Foundation funds a program aimed at discovering enzymes that will be safe to introduce into the human body, and have achieved some degree of success in recent years.

The second theme in biomedical remediation research is the delivery of suitable enzymes to where they are needed: the lysosomes within our cells. Fortunately, this is an area in which many researchers are already hard at work. There exists a category of genetic disorders, the lysosomal storage diseases, in which the lysosome is dysfunctional or lacks one or more vital enzymes. Advances in repairing these conditions by delivering the correct enzymes to a patient's lysosomes are also applicable to biomedical remediation aimed at rejuvenating the malfunctioning, clogged-up lysosomes of the elderly.

Here's a recent paper from the ahead of print queue at Rejuvenation Research:

New Strategies for Enzyme Replacement Therapy for Lysosomal Storage Diseases

Enzyme replacement therapy is an established means of treating lysosomal storage diseases. Infused enzymes are normally targeted to the lysosomes of affected cells by interactions with cell-surface receptors that recognize [portions of the] enzymes. Therefore, we have investigated alternative strategies ... These strategies for delivering lysosomal enzymes could also be used to target nonlysosomal proteins or enzymes identified for bioremediation of other conditions.

This is an age of barnstorming and hacking in biotechnology - there are lot of very clever and complex things that can be accomplished with the present day tools and knowledge of human biochemistry. The paper above also illustrates the wide application of many areas of life science research. Tools aimed at specific human conditions may in the future be adapted to serve as part of a technology capable of repairing some of the damage of aging.

Grubb, J., Vogler, C., & Sly, W. (2010). New Strategies for Enzyme Replacement Therapy for Lysosomal Storage Diseases Rejuvenation Research DOI: 10.1089/rej.2009.0920

Advanced glycation end-products (AGEs) seem to be important in aging, their buildup effectively a form of damage that harms cellular processes in a number of ways. Here, researchers suggest that an AGE precursor chemical is also problematic: "Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20393592

This release via ScienceDaily summarizes the goals of present day calorie restriction research: "Organisms from yeast to rodents to humans all benefit from cutting calories. In less complex organisms, restricting calories can double or even triple lifespan. It's not yet clear just how much longer calorie restriction might help humans live, but those who practice the strict diet hope to survive past 100 years old. ... calorie restriction influences the same handful of molecular pathways related to aging in all the animals that have been studied. Aware of the profound influence of calorie restriction on animals, some people have cut their calorie intake by 25 percent or more in hopes of lengthening lifespan. [Researcher Luigi Fontana] is less interested in calorie restriction for longer life than in its ability to promote good health throughout life. ... Right now, the average lifespan in Western countries is about 80, but there are too many people who are only healthy until about age 50. We want to use the discoveries about calorie restriction and other related genetic or pharmacological interventions to close that 30-year gap between lifespan and 'healthspan.' However, by extending healthy lifespan, average lifespan also could increase up to 100 years of age."

Link: http://www.sciencedaily.com/releases/2010/04/100415141123.htm

By way of a reminder, the Humanity+ UK 2010 conference will be held in London later this month. Those of you familiar with the evolution of the transhumanist community over the past decade will recognize most of the names on the conference agenda. Biomedical gerontologist Aubrey de Grey is presenting on "human regenerative engineering - theory and practice", so if you have the chance, you might consider attending.

The UK chapter of Humanity+, an organisation dedicated to promoting understanding, interest and participation in fields of emerging innovation that can radically benefit the human condition, announced today that registrations are on track for record attendance at the Humanity+ UK2010 conference taking place in Conway Hall, Holborn, London, on April 24th.

"Approaching 200 attendees are expected to take part in a full day of thought-provoking lectures, discussions, Q&A, and breakouts, led by a line-up of world class futurist speakers", said David Wood, H+UK meetings secretary. "Participants have registered from as far afield as Poland, Sweden, Croatia, Portugal, Germany, Belgium, Holland, Ireland, and the USA. The Humanity+ movement, previously known as the World Transhumanist Association, is coming of age."

"Transhumanism is both a reason-based philosophy and a cultural movement that affirms the possibility and desirability of fundamentally improving the human condition by means of science and technology," said Max More, founder in 1988 of the Extropy Institute think tank ideas market for the future of social change. "Transhumanists seek the continuation and acceleration of the evolution of intelligent life beyond its current human form and limitations by means of science and technology, guided by life-promoting principles and values."

Transhumanism is simple common sense as applied to thinking about technology, the human condition, and the future. We look back to see that life was harder in the past: people were less wealthy and less capable, living lives made narrow by comparative lack of choice and tool-aided ability. Today we are not just better off, but actually better than our ancestors: healthier, more broadly skilled, more knowledgeable, and longer-lived. This is the case precisely because technology has advanced, expanding our options and the ability to create better lives. Increasing the capabilities and efficiency of human technology is a great good, as better tools can be used to help us to become better in every way - to enable lives of more choice, greater capabilities, less suffering, and greater wealth.

The result of most interest here is, of course, the way in which progress in applied biotechnology will enable us to greatly extend the healthy human life span. We look to a future in which life science researchers step beyond incremental improvements in slowing down the wear and tear of life, to begin actively identifying and repairing the biochemical damage of aging. They will build technologies of rejuvenation that can restore vigor and youthful function to the aged. This is a grail of transhumanism: the ability to turn resources into more time spent alive and in a good health.

A general interest article on transhumanist visions of the future and immortality in the sense of the continued repair and reversal of aging through medical technology: "Immortality could be sneaking up faster than we can believe. Barely a month goes by without some new advance in organ replacement, and a recent operation to replace a boy's windpipe with one generated from his own stem cells was called 'embarrassingly simple' by the specialist in charge. Further breakthroughs could be made by the SENS Foundation, led by the radical immortalist Aubrey de Grey, with a brutally simple plan to give humans an unbeatable protection against cancer. This involves limiting human cells' ability to divide at cancerous levels, with regular top-ups from externally grown cells replacing worn-out tissue. If these technologies can hold to their promise, biological immortality, perhaps the most cherished goal of the transhumanists, may be with us in a few decades. A loose grouping of scientists, philosophers and sympathisers, with organisations such as the Oxford Future of Humanity Institute and Humanity+, transhumanists urge human progress through radical technological enhancement. With regards to immortality, I'm certainly a sympathiser: if a dictator was murdering tens of millions of people right across the world, we'd gladly do anything to overthrow him. And yet ageing, as eloquently put by the transhumanist philosopher Nick Bostrom, is a tyrant that kills us by the cartload - and what do we do to stop it?"

Link: http://www.guardian.co.uk/commentisfree/2010/apr/15/transhumanism-biological-immortality

It will be possible to replace the functions of some organs with machines in the near future, this advance accomplished on much the same timescale as the creation of tissue engineered replacement organs: "An artificial pancreas system that closely mimics the body's blood sugar control mechanism was able to maintain near-normal glucose levels without causing hypoglycemia in a small group of patients. The system, combining a blood glucose monitor and insulin pump technology with software that directs administration of insulin and the blood-sugar-raising hormone glucagon, was developed at Boston University (BU). The first clinical trial of the system was conducted at Massachusetts General Hospital (MGH) and confirmed the feasibility of an approach utilizing doses of both hormones ... Large doses of glucagon are used as a rescue drug for people with severely low blood sugar. Our system is designed to counteract moderate drops in blood sugar with minute doses of glucagon spread out throughout the day, just as the body does in people without diabetes." The future for this sort of technology is one of miniaturization, falling cost, and the possibility of incorporation into the body as an implanted device.

Link: http://www.eurekalert.org/pub_releases/2010-04/mgh-nap041210.php

As noted by Sonia Arrison, the Pope is not in favor of engineered human longevity. Surprise, surprise:

Modern medical science strives, if not exactly to exclude death, at least to eliminate as many as possible of its causes, to postpone it further and further, to prolong life more and more. But let us reflect for a moment: what would it really be like if we were to succeed, perhaps not in excluding death totally, but in postponing it indefinitely, in reaching an age of several hundred years? Would that be a good thing? Humanity would become extraordinarily old, there would be no more room for youth. Capacity for innovation would die, and endless life would be no paradise, if anything a condemnation.

Which nicely frames three of the common mistaken, knee-jerk objections to greater longevity: the Tithonus Error, predictions of stagnation, and the expectation of boredom. These and other objections are easily answered - visit the links in this paragraph to see more of a discussion. One shouldn't expect a vested interest like the wealthy hierarchy of a modern organized religion to meaningfully engage the pro-longevity side of the debate, however. This will be to their detriment in the end: siding against medical progress and with the massive death and suffering caused by aging is a short term, conservative position for any organization, no matter how greatly they benefit from the status quo.

I'm dimly aware enough of the foundation of Christian theology to know that death and immortality have a central place in that grand structure of delusion and desire. It is not unexpected to see the vested power structure at the head of it all feel threatened by the prospect of a secular takeover of this core portion of their domain. One can look back at the history of cosmology to see how this process plays out between a rich and powerful faith and comparatively poor (but ultimately unstoppable) scientists and technologists. We can hope to see less in the way of murder this time round, though it could be argued that all attempts to hold back progress in the development of longevity science are a form of indirect mass murder.

I suspect that the fixation upon mortality sells short the diversity of the religious impulse, however - which makes position statements like that of the Pope above look very much like ossified short-termism within the upper reaches of the Catholic Church. Religion is a vast pearl grown over tens of thousands of years around a wide range of unsatisfactory irritants within the human condition and the nature of reality. Death is but one of those irritants, and Christianity but one gloss on the pearl's outer layer. For so long as humans remain largely human in the structure of mind and psychology, there will be a great demand for religion of one sort or another.

No matter your opinion on the topic, this is as it is, and one has to learn to live with it. The future is clear: death and all things pertaining to it will one day be as much in the domain of life scientists as cosmology is now in the domain of astrophysicists. The sooner we get there, the better.

The Tithonus Error is the widespread and mistaken belief that extending the human life span will result in us being aged and decrepit for longer. This is not the case, however: engineered longevity can only be accomplished by repairing or reducing cellular and biochemical damage - which means you will be younger for longer. At In Search of Enlightenment, you'll find an examination of the roots of the Tithonus Error: "There is an irrational public predisposition to regard research on specific late-life diseases as marvelous but to regard research on aging, and thus all late-life diseases together, as a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce. ... I am working on a new paper [that] examines how misperceptions about the present and future state of global health are themselves major obstacles to tackling aging. Because [imagined simulations of the future] are based on memories, medical research that proposes to eliminate a disease is much more likely to invoke hedonic experiences in our simulations then is a medical intervention that retards aging. ... our inability to make accurate, sensible simulations of what a future of retarding human aging would entail (for both the developed and developing world) is itself one of the greatest obstacles to prioritizing aging research. And this problem needs to be redressed."

Link: http://colinfarrelly.blogspot.com/2010/04/prospection-errors-are-obstacles-to.html

From the University of Bristol: "Synthetic biology is about improving our ability to engineer biology, and to engineer biology you have to understand the underlying chemistry. ... We look at natural molecules and ask, 'How does nature do this?' And then we take those key features and build them into synthetic molecules to mimic the natural ones. ... Specifically, Woolfson is trying to capture features of the materials that hold cells together and which provide the environment to turn collections of cells into tissues such as skin, liver and networks of nerves. This 'glue' is called the extracellular matrix (ECM). However, the ECM is made up of large, complicated molecules with lots of different chemistries, so Woolfson began to investigate whether it would be possible to build something similar to ECM, but out of much simpler and more chemically accessible materials. That was 10 years ago. Today he has developed nano-sized proteins that have been designed to 'self assemble' into long, spaghetti-like strings, which then become entangled to form a gel. ... The result is a hydrogel (a gel in which the liquid constituent is water) made up of these tiny, spaghetti-like strings of proteins which acts as a scaffold to support cell growth in much the same way as the ECM does."

Link: http://bristol.ac.uk/news/2010/6928.html

Back in 1998, I was only a few years past my first moment of wakefulness:

One day, you wake up to realize that a particularly vital assumption about the world is wrong. Everyone who buys into it is wrong. Which is almost everyone in the world. Everything in the world that depends on it is wrong. Which is almost everything in the world. Now what? ... So, one day, you wake up to realize that aging is the worse bane suffered by humanity, and the people of the world sleepwalk through an unending holocaust of suffering and death caused by the decay of their bodies. Furthermore, it quickly becomes apparent that large-scale work over a few decades will plausibly lead to medical technologies that prevent age-related frailty, disease and death. Acceptance of aging in this circumstance is like a slow-motion mass suicide, day after day after day.

To do nothing in the face of this was unacceptable, but I spent those first years stuck in the morass that was (back then at least) any attempt to find useful information about the state of medical technology, aging science, and the future of human longevity. Of course there was also the matter of figuring out, in between dealing with life's hideous slings and arrows, just what it was I was going to do about it all. How could I meaningfully contribute? It took a while before the Longevity Meme coalesced from those experiences.

In 1998, whilst I wandered amongst the blind, Ben Bova published a book called Immortality: How Science Is Extending Your Life Span - and Changing The World. I didn't read it then, and in fact only recently noticed that it even existed. But you should take a look, because it encapsulates many of the same arguments, predictions, and positions put forward by longevity advocates in the years since:

Do you want to live to be 200? How about 500? Maybe forever? Ben Bova, famed science fiction author and futurist, predicts that within the lifetimes of many people alive in 1998, molecular biology and genetics will reveal the secrets of cellular immortality, freeing people of the "threescore years and ten" most of us are allotted. Further, Bova asserts in Immortality, we will be living those long lives in healthy, youngish bodies, subject only to death by accident. To back up this claim, Bova offers a nice, clear overview of how genetics has come to the brink of science fiction, made accessible to readers unfamiliar with the terminology through the use of explanatory sidebars and basic definitions. If you find yourself doubting this prediction, two things might make you reassess your opinion: (1) Ben Bova was right when he foretold the advent of the Internet, solar-powered satellites, electronic books, and many other wonders of the 20th century, and (2) in an extraordinary 50-year time line, he shows how fast and furious technological developments have come - including things that would have been deemed impossible mere months before they happened. After showing how science is laying the groundwork for achieving incredible human longevity, Immortality examines the ways society, government, the environment, and personal responsibility might change in the face of it. No pessimist or technophobe, Bova assures us that immortal people will (by necessity) become more farsighted and thoughtful about their lives and the lives of others.

These points were being made before Bova's publication in transhumanist and other futurist forums since the advent of the internet, and by forward looking thinkers even before that. But it's worth remembering that this past decade of advances in longevity science, many new publications on engineered longevity, a growth in advocacy for healthy life extension, and multi-million dollar fundraising by organizations such as the Methuselah Foundation didn't just materialize from nothing. It's another link in a chain that stretches back for a good number of years.

As illustrated by the reliability theory of aging, we are complex machines, and our life expectancy is a function of the pace at which we accumulate damage. For example, one contribution to rising life spans over the past century was the elimination of much of the burden of chronic disease throughout early life and middle age. Here, however, is an example of another, less common form of damage that nonetheless has the expected end result: "Although more children today are surviving cancer than ever before, young patients successfully treated in the 1970s and 80s may live a decade less, on average, than the general population ... The study, based on a computer model, is the first to estimate the lifetime toll of childhood cancer and the grueling but increasingly successful treatments for diseases such as kidney and bone cancers, leukemia, and brain tumors. About 10,000 children and adolescents are diagnosed with cancer annually, and the five-year survival rate has risen to about 80 percent overall. ... The study is based on how children were treated in the 1970s and early 1980s. It is our hope that when we see data from more recent cohorts of patients, there will be improved life expectancy as a result of some changes that pediatric oncologists have made."

Link: http://www.eurekalert.org/pub_releases/2010-04/dci-ccs040510.php

From the SENS Foundation: "To develop an unbreachable defense against cancer, SENS Foundation is pursuing the WILT (Wholebody Interdiction of Lengthening of Telomeres) strategy (OncoSENS) of systematically deleting genes essential to the cellular telomere-maintenance mechanisms (TMM) from all somatic cells, while ensuring ongoing tissue repair and maintenance through periodic re-seeding of somatic stem-cell pools with autologous TMM-deficient cells whose telomeres have been lengthened ex vivo. In addition to the deletion of one or more genes coding for essential element(s) of the telomerase holoenzyme, success will also require the deletion of some essential element of the machinery for the Alternative Lengthening of Telomeres (ALT) phenomenon, observed in a minority of cancer cells. Heretofore, the identity of that machinery has been elusive. Yeast cells have the ability to lengthen telomeres through a telomerase-independent mechanism involving telomere recombination, and there has been evidence for some time suggesting that ALT cancers lengthen telomeres through a similar process." The article goes on to look in detail at one plausible candidate mechanism for ALT, and how this new knowledge might be incorporated into WILT.

Link: http://www.sens.org/node/739

Over at Ouroboros, you'll find a brace of posts reporting on the first Bay Area Aging Club meeting. There's actually quite a concentration of both mainstream and more ambitious biogerontologists and other life science researchers and advocates in that region, what with the Buck Institute for Age Research, Cynthia Kenyon's lab at UCSF, and the legacy of a few years of SENS-related conferences, fundraising meetings, and organizational work.

Today I’m attending the first Bay Area Aging Club at UCSF’s Gladstone Institute. BAAC is a meeting of local scientists working in biogerontology and related fields ... The idea is that the conference will be held regularly (every 6 months or so), allowing frequent discussion of recent progress and ongoing work, and encouraging networking and collaboration between Bay Area biogerontologists. The conference is drawing from a fairly big population - everyone at the Buck Institute, comprising the members of 15 or so labs, and at least as many from Berkeley, Stanford, UCSF; I’d estimate more than 300 scientists.

Networking is what makes the world go round, and the health of a field is measured by the frequency and quality of its conferences. Here are links to the meeting reports:

Bay Area Aging Club - Session I: Model organisms & model systems

Adolfo Sanchez-Blanco began with the observation that lifespan [in nematode worms] is variable, even among clonally identical individuals kept under identical conditions. With genetics and environment taken out of the picture, what makes some individuals live longer than others? [He] has identified [several genes] whose expression at middle age strongly predicts remaining lifespan.

Bay Area Aging Club - Session II: Sirtuins; telomeres

Jue Lin (Blackburn Lab, UCSF): Telomere length maintenance and aging-related diseases. This talk described work that builds on significant progress, from this lab and others, demonstrating relationships between telomere length and stress, psychological outlook, and lifespan. Lin reviewed evidence that perceived stress is correlated with telomere length in white blood cells (consistent with previous results showing a relationship with intrusive thoughts).

Bay Area Aging Club - Session III: Calorie restriction; protein aggregation

Protein aggregates are a hallmark of many age-related neurodegenerative diseases, leading to the hypotheses that the cellular mileu changes with age in a manner that causes native, aggregation-prone proteins to form aggregates. [Delia David] used mass spectrometry to identify a subset of normal worm proteins that aggregate as a function of age. As with the proteins associated with neurodegeneration, specific proteins aggregate in specific cell types. Mutations that extend lifespan (such as daf-2) decrease aggregation, and tend to downregulate the expression of genes encoding aggregation-prone proteins.

Bay Area Aging Club - Panel discussion: Free radical theory of aging

At the end of the meeting, Martin Brand and Stuart Kim led a group discussion about the free radical theory of aging. Martin began the discussion by pointing out that "after 50 years, you would expect a theory to accumulate enough evidence to convince us that it's true or false - but the fact that we're still discussing it today means that hasn't happened." I'm paraphrasing slightly, but that's the general idea.

Interesting stuff, and worth a look.

How is it possible for evolutionary selection to favor genetic variants beneficial in human old age, long after reproduction is impossible? An open access paper examines this question: "Evidence points towards the existence of a strong heritable component of human longevity. Around a quarter to a third of the variability of lifespan can be attributed to the action of genes. One of the best examples of a gene affecting survival in old age is the apolipoprotein E gene APOE. ... One of the major ideas in the evolutionary theory of ageing is the suggestion that, because the force of natural selection declines with age, alleles with deleterious effects seen only at older ages can reach higher frequencies than those that have their effects earlier in life. Therefore, if a gene exerts an effect only after the end of the reproductive phase of the lifespan it has been thought unlikely that it could have been subject to significant direct selection pressure ... It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848859/

Via EurekAlert!, another example of testing stem cells and heart regeneration: "Some patients with heart muscles seriously affected by coronary heart disease may soon be able to benefit from an innovative treatment. Researchers [are] evaluating the safety, feasibility and efficacy of injecting stem cells into the hearts of patients while they are undergoing coronary bypass surgery. These stem cells could improve healing of the heart and its function. The IMPACT-CABG (implantation of autologous CD133+ stem cells in patients undergoing coronary artery bypass grafting) protocol evaluates this experimental procedure, which is destined for patients suffering from ischemic heart disease, in which the blood supply to the heart is decreased and associated with heart failure. These patients undergo open-heart coronary bypass surgery, performed by the medical team to improve perfusion of the heart muscle. A few weeks ago, the first patient received progenitor CD133+ stem cells isolated from his bone marrow and enriched, [and] has been doing very well ever since. Already, improvement has been noted in the contraction capacity of his heart, which has improved its ability to pump blood."

Link: http://www.eurekalert.org/pub_releases/2010-04/chdl-hcy_1041110.php

Recellularization is a transplant preparation process that begins by stripping living cells from donor tissue - such as a heart valve, an entire heart, a trachea, and so forth - to leave behind the extracellular matrix as a scaffold. That scaffold is then seeded with the transplant recipient's own cells, which grow throughout its structure to reform the original tissue. This has proven to be an excellent way to prepare transplants that will not trigger immune rejection, even for xenotransplantation between species. In recent years, we've seen a number of successful recellularized transplants in humans:

• Transplant of a recellularized trachea
• Transplant of recellularized heart valves

Recellularization work is becoming more widespread in the laboratory. Numerous groups are now incorporating this strategy into their own research programs, such as the bone tissue engineers I mentioned not so long ago. But today let me point out a group who are working to generate blood vessels via this methodology:

Using adult stem cells, researchers have created functional blood vessels that could one day replace synthetic grafts often required in various vascular bypass surgeries

...

"It was our idea to create a more biological conduit that would avoid the problems of synthetic grafts and give patients a better alternative," said McIlhenny. "The significant finding is that we can build a blood vessel from donor tissue and an animal's own adult stem cells. Potentially, patients requiring bypass surgery could receive optimized grafts that would reduce their future complications."

Researchers grew rabbit adult stem cells on human vein scaffolds in the laboratory. The team removed all cells from sections of human saphenous veins, which left a tube consisting only of the protein scaffolding that supported the cells. Because the scaffolding contains no cells; there is less risk the immune system will reject it.

Great shortages and delays exist for people who need organ transplants - largely imposed by regulatory bodies and laws that forbid an open market in body parts or paid agreements between donor and recipient. So organs that might otherwise have been used go to the grave, and funds that might have benefited the deceased's next of kin are spent on other things; yet another way in which unelected bureaucrats destroy value and ensure suffering in the field of medicine. One way in which recellularization might alleviate these human-caused issues is by opening the door to safe and widespread use of animal organs for transplant.

Greater understanding of the immune system means a greater ability to reprogram its components - such as errant immune cells that cause autoimmune diseases. From EurekAlert!: a study "describes a unique therapeutic 'nanovaccine' that successfully reverses [type 1] diabetes (T1D) in a mouse model of the disease. In addition to providing new insight into diabetes, the research also reveals an aspect of the pathogenesis of the autoimmune response that may provide a therapeutic strategy for multiple autoimmune disorders. ... [Researchers] wanted to find a way to counteract the harmful autoimmune response without compromising general immunity. They discovered that our bodies have a built-in mechanism that tries to stop the progression of autoimmune diseases like T1D. Essentially, there is an internal tug-of-war between aggressive T-cells that want to cause the disease and weaker T cells that want to stop it from occurring ... The researchers also developed [a] nanotechnology-based 'vaccine' that selectively boosted the weak white blood T cells, enabling them to effectively counter the damage caused by their overactive T cell relatives. ... their nanovaccine blunted T1D progression in prediabetic mice and restored normal blood sugar in diabetic mice. ... If the paradigm on which this nanovaccine is based holds true in other chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and others, [nanovaccines] might find general applicability in autoimmunity."

Link: http://www.eurekalert.org/pub_releases/2010-04/cp-ra040510.php

This seems like a logical next step for tissue printing technologies: "researchers have rigged up a device that can spray skin cells directly onto burn victims, quickly protecting and healing their wounds as an alternative to skin grafts. They have mounted the device, which has so far only been tested on mice, in a frame that can be wheeled over a patient in a hospital bed. ... A laser can take a reading of the wound's size and shape so that a layer of healing skin cells can be precisely applied. ... We literally print the cells directly onto the wound. We can put specific cells where they need to go. ... [Researchers] dissolved human skin cells from pieces of skin, separating and purifying the various cell types such as fibroblasts and keratinocytes. They put them in a nutritious solution to make them multiply and then used a system similar to a multicolor office inkjet printer to apply first a layer of fibroblasts and then a layer of keratinocytes, which form the protective outer layer of skin. ... The sprayed cells also incorporated themselves into surrounding skin, hair follicles and sebaceous glands, probably because immature cells called stem cells were mixed in with the sprayed cells."

Link: http://ca.news.yahoo.com/s/reuters/100408/science/science_us_wounds_printer

For so long as the present prodigious rate of technological progress keeps up, we will continually be entering the era of living longer. Each new generation benefits from medical technology unavailable to their parents, and accumulates the biochemical wear and tear of degenerative aging more slowly as a result. A recent New Scientist article contains this demographic factoid:

Of all the people in human history who ever reached the age of 65, half are alive now.

This is the result of a grand increase in wealth across the world over the past two centuries: more people, higher living standards, technological innovation, and better medicine combining to yield a steady increase in human longevity. Slow and steady might be slow and steady, but it soon enough creates a world very different from that inhabited by our grandparents when they were young.

Yet there is every reason to believe that what lies ahead is not more of the same, but a far more rapid leap in capabilities and outcomes. We don't stand on a flat slope of progress, but rather on the flatter, earlier sections of an exponential curve. The biotech revolution of the 21st century will do for our lifespans what the computing revolution of the past fifty years did for human communications:

It's quite likely that we'll all be wildly, humorously wrong about the details of implementation, culture and usage, but - barring existential catastrophe or disaster - [these technological capabilities] will come to pass. The human brain will be reverse engineered, simulated and improved upon. The same goes for the human body; radical life extension is one desirable outcome of this engineering process. We will merge with our machines as nanotechnology and molecular manufacturing become mature technologies. Recursively self-improving general artificial intelligence will develop, and then life will really get interesting very quickly. And so forth ... the question is not whether these things will happen, but rather when they will happen - and more importantly, are we going to be alive and in good health to see this wondrous future?

Whether we get to see medical technologies capable of repairing the damage of aging in the human body is very much up to us. The path is clear, but too few researchers are presently working on it. The public at large are not particularly aware yet that the possibility exists, or that meaningful progress is plausible within their lifetimes. So we will see the future of greatly increased longevity and the reversal of aging if we work for it, and we won't if we sit back and let things slide.

Have you donated to Methuselah Foundation or SENS Foundation recently? You might give it some thought.

Empires end when an entrenched elite can spend from the public purse and take on debt without immediate consequence or forethought, destroying the value of their currency in the process. Assuming (perhaps optimistically) that present economic empires survive the next couple of decades, a combination of foolish promises and increasing human longevity will be the rock that sinks them. From Reuters: "Like the subprime crisis faced by banks in 2008, the risk of people living for up to 20 years after retirement seems to have crept up on an industry based on using historical data to calculate people's chances of an early death. Now, pension funds and insurers say the mounting burden of protracted pensions payments is increasingly concentrated on a small group of providers: them. ... Nowhere better can the process be seen than in Britain, which is facing a crisis resulting from a combination of pension reforms and increased life expectancy. ... The many arguments in favor of a sovereign bond linked to longevity rest on one fundamental expectation: if pension providers can't pay, or become insolvent, governments will have to. Longevity bonds could make the process neater, and more politically palatable, than the collapse of a pension provider." The problem is not that some groups made bad bets, or that many people relied upon those bets being good. The problem is that these groups and their supporters can conspire with governments to bail themselves out with public funds and debt heedless of consequences.

Link: http://www.reuters.com/article/newsOne/idUSTRE6360LP20100407

From the MIT Technology Review, a look at another form of first generation immune therapy aimed at cancer: "Last year marked a first for engineered antibodies - the European Commission approved a new cancer drug called Removab (catumaxomab), an antibody specially designed to grab both cancer cells and immune cells in such a way that the immune cell can kill the cancer cell. (The drug is undergoing testing for U.S. Food and Drug Administration approval.) Now a handful of similarly complex molecules, dubbed 'bispecific antibodies' for their ability to target two things at once, are in clinical trials. The two arms of these antibodies work together in different ways to treat cancer or other diseases, by bringing together two types of cells, as with Removab, by targeting two different types of receptors on the surface of a cell, or even using one arm to deliver drugs to specific cells targeted by the other. ... While the concept of bispecific antibodies has been around for decades, the approach has only recently shown clinical success. The field has been driven forward by new ways of designing and making the antibodies, which take advantage of advances in protein engineering, as well as the success of single-target antibodies, such as herceptin, that are already on the market." This is an example of the way in which targeting technologies and new strategies from the biotechnology labs are slowly filtering into the old school drug development pipeline.

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=24970

The future of cancer treatment is targeting: killing only the cells you want to kill, with no side effects or harm. Discrimination and control is the benefit brought by advances in biotechnology, and the results presently tested in the laboratory are a world removed from even the best contemporary chemotherapy or radiation treatment.

A number of different technology platforms are under development within the paradigm of targeted cell killers:

• First is the nanoparticle: comparatively simple structures whose behavior researchers can expect to fully understand. They only do what they are designed to do, which is typically to act as an inert link between a homing device and a kill mechanism.
• Second is the engineered virus, altered natural self-replicators that are restricted to working their characteristic havoc only upon the target cell type.
• Thirdly, we have engineered immune cells. The immune system already tries to attack and destroy cancers, but some are invisible to it. If immune cells can be given the right biochemical tools to recognize the enemy, then they will fight and win.

You might think of these strategies as falling on a scale of complexity: at the level of nanoparticles, researchers are working with systems simple enough for outcomes and side-effects to be confidently predicted or quickly established in the laboratory. Viruses are more capable and more complex, and the immune system yet more capable and complex. The trade off here lies in speeding development by use of an existing complex biological system that has already evolved to perform the task you have in mind versus the greater difficulty of predicting how that system is going to behave in the field as a therapy.

Via Singularity Hub, I see that trials are fairly advanced for the first generation of engineered immune cell based therapies for cancer; pull out cells from the patient, alter them to better kill cancer cells, then return them to the body.

It's been almost a year since we covered Dendreon announcing its successful Phase III clinical trials for its prostate treatment Provenge. Now, the Seattle based company is continuing its work of getting Provenge, also known as Sipuleucel-T, to the market. The revolutionary treatment for metastasized prostate cancer uses the body's own immune system to hunt down and kill cancer cells that have spread beyond the organ. Upgrading the immune system's T-cells with special proteins, a process called Active Cellular Immunotherapy (ACI), lets them hunt down cancer cells via the antigens embedded on their surface. ACI seems to work well for prostate cancer and Dendreon is expanding it to treat bladder, breast, ovarian and colon cancer with Lapuleucel-T (which has already completed Phase I trials).

...

Though I’m certainly impressed with Sipuleucel-T/Provenge and excited by Lapuleucel, I think the real story here is ACI. It may take us years before nanoparticles can actively effect the growth of cancer. Immune system cells, however, are a form of quasi-nanotechnology that we can tap into in the near term.

That multiple competing strategies exist and are fairly advanced is a good sign for the future of this field: in the past few years, I have seen significant advances in cancer therapies based on targeting via nanoparticle, virus, and immune cell. All more reasons as to why I'm not too concerned about the cancers that wait in my personal future.

Manipulating the machinery of mitochondria - the respiratory chain that turns food into the chemical ATP that is used to power cellular biochemistry - can extend healthy life in a variety of species. Here, researchers dig deeper into the mechanisms by which this happens, finding that there are more than one: "In Caenorhabditis elegans longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation [that] reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We [compared] nuo-6(qm200) [to] nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, [as] well as expression of superoxide dismutases, mitochondrial heat shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. ... Most importantly, we found that [the] lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20346072

Via the Methuselah Foundation blog: "Today Methuselah Foundation launched the NewOrgan Prize, the Foundation's new longevity prize specifically focused on advancing the development of replacement tissues and organs for humans. Its goal is to accelerate advances in regenerative medicine, which will become the standard of care for replacing all tissue and organ systems in the body within 20 years, according to the U.S. Department of Health and Human Services. The first research team to construct a whole new complex organ (heart, kidney, liver, lung, pancreas) made from a person's own cells - one that is functionally equivalent and successfully transplanted - will be awarded the NewOrgan Prize. The goal of the Methuselah Foundation NewOrgan Prize is to achieve this medical breakthrough within the next 10 years. Today's launch is a call to action for competitors, candidates and contributors who want to participate in this crucial medical challenge aimed at extending healthy human life. ... Based on our success in spurring medical advances with incentives provided by the original Methuselah Mouse prize, we anticipate that over $10 million will be raised by the time the NewOrgan Prize criteria is met - and the prize presented - to the leading medical R&D team. At minimum, $1 million will be awarded to the research team that develops a whole new human organ that is functional and successfully transplanted."

Link: http://blog.methuselahfoundation.org/2010/04/methuselah_foundation_launches_neworgan_prize.html

I see that the SENS Foundation is devoting more space to promoting their academic initiative:

The study of human aging requires an implementation of translational approaches which many students are simply not exposed to in their general education. Current educational paradigms present an opportunity to easily and inexpensively train students in these methods and cultivate interest in aging research. These assumptions have led to the formation of SENS Foundation's Academic Initiative (SENSFAI), a student-focused research and development program designed to recruit talented student scientists into the broad field of longevity science with a specific focus on the SENS engineering platform. Since the launch of its pilot studies in the fall of 2008, SENSFAI has demonstrated its potential as a viable research entity. Growing from a humble beginning of only three volunteer mentors and five students, the program has expanded to its present base of over 50 students and volunteers operating in nine countries worldwide, and offers a novel approach for promoting student excellence in academia.

As is true of any field of human endeavor, even very complex ones, a great deal of the labor in life science research does not require highly experienced and expensive staff. Advanced students are knowledgeable and smart enough to get the job done, for example. In addition, work like testing many different bacterial enzymes against their ability to break down unwanted biochemicals that build up with aging, or building computer models to calculate expected behavior in a specific biological system, can be made faster by allowing many different people to work in parallel - exactly the situation where pulling in more capable but less experienced people from academia is sensible.

In any case, the SENS Foundation is profiling one of the SENSFAI student researchers in their news section:

Could you briefly describe your current research efforts for SENSFAI and how they support the core mission of the SENS Foundation?

My current research efforts is on the characterization of the roles of Nitric Oxide (NO) in apoptosis and apoptotic-like cell death pathways in Chlamydomonas reinhardtii, a green algae. We hope to be able to determine the levels of NO and mechanism of induction of cell death in this organism. There have been numerous characterized mechanisms of NO's mediation and also, interestingly, inhibition of apoptosis in animal cells, and our results could provide more insight into these emerging mechanisms such that at the long run, we would be able to understand how NO can be utilized therapeutically to enhance the quality of human life.

Do you think you involvement with SENSFAI will influence your future career? How so?

Absolutely. My involvement with SENSFAI has led me into the path of pursuing an MD/PhD degree and thus perpetuating aging research.

Everyone wins: the SENS Foundation moves ahead with its research, and the students gain experience and connections that cannot be obtained through a standard university curriculum.

One approach to stem cell therapy is to try to order existing stem cells to do more work, accomplished by introducing signaling molecules into the body - a drug, in other words. This methodology has reached the point of early clinical trials, as indicated in this press release: "Clinical-stage regenerative medicine company Juventas Therapeutics Inc. [has] started enrolling patients in a Phase 1 clinical trial to evaluate the safety and efficacy of its leading stem cell factor for treating heart failure. In preclinical studies of heart failure in pigs, JVS-100, as the factor is known, significantly increased cardiac function by promoting cell survival and increasing blood vessel formation in damaged hearts. JVS-100 works by encoding Stromal Cell-derived Factor-1 (SDF-1), a growth factor that in adults recruits stem cells from the bone marrow to create new blood vessels. The JVS-100-treated pigs showed significant improvements in cardiac function. ... We've led with heart failure because that's where our preliminary data was, and it's a great clinical opportunity. We also have strong data in the area of peripheral vascular disease and cosmetic wound healing. ... The factor can increase blood flow for patients who have peripheral vascular disease and accelerate wound closure and prevent scarring for patients who have had cosmetic surgery [so] we're looking to move both those toward clinic in the near future."

Link: http://www.medcitynews.com/2010/04/juventas-therapeutics-starts-phase-1-trial-for-heart-failure-therapy/

A good review paper: "Our understanding of autophagy has expanded greatly in recent years, largely due to the identification of the many genes involved in the process, and to the development of better methods to monitor the process, such as GFP-LC3 to visualize autophagosomes in vivo. A number of groups have demonstrated a tight connection between autophagy and mitochondrial turnover. Mitochondrial quality control is the process whereby mitochondria undergo successive rounds of fusion and fission with a dynamic exchange of components in order to segregate functional and damaged elements. Removal of the mitochondrion that contains damaged components is accomplished via autophagy (mitophagy). Mitophagy also serves to eliminate the subset of mitochondria producing the most reactive oxygen species, and episodic removal of mitochondria will reduce the oxidative burden, thus linking the mitochondrial free radical theory of aging with longevity achieved through caloric restriction. Mitophagy must be balanced by biogenesis to meet tissue energy needs, but the system is tunable and highly dynamic. This process is of greatest importance in long-lived cells such as cardiomyocytes, neurons, and memory T cells. Autophagy is known to decrease with age, and the failure to maintain mitochondrial quality control through mitophagy may explain why the heart, brain, and components of the immune system are most vulnerable to dysfunction as organisms age."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20357180

Do changes in nuclear DNA significantly affect the course of aging? A good question, and one that is still open and energetically debated in the scientific community. How about epigenetic changes, mechanisms that alter the process of producing proteins from genetic blueprints without changing the genes themselves, such as those involving DNA methylation? Insofar as degenerative aging is concerned, are epigenetic changes a cause, a consequence of other, more fundamental changes, or a mix of both cases? These are also good questions, and still open to debate or new evidence.

I noticed two open access papers on epigenetic changes in aging today, the first of which begins with this statement:

Aging is arguably the most familiar yet least-well understood aspect of human biology.

Which is quite true. Fully understanding aging - a set of massively complex changes in a massively complex system - will take a long time, biotechnology revolution or no biotechnology revolution. But full understanding is not needed for significant progress to occur in the development of medical technologies to repair and reverse the damage of aging. Just as for other fields, there are engineering strategies that can sidestep ignorance and build good solutions based upon what is actually known. Our ancestors built good, working bridges for thousands of years prior to the advent of modern architectural and materials science, for example - they didn't have a full understanding, yet got the job done by forging ahead and building upon what they did know. Today, life science researchers know more than enough about the forms of damage caused by aging to proceed with development: it is perfectly possible to work towards biological repair in the absence of a complete understanding of all the interactions and processes of aging. Fixing the damage we see will be sufficient - we don't have to fully understand all of the very complicated ways that this damage progresses into disease and death.

But take a look at the papers - I think you'll find them an interesting example of an open and debated question in aging science.

The Janus face of DNA methylation in aging

The role of epigenetics in aging and age-related diseases has gained interest given recent advances in the understanding of how epigenetic mechanisms mediate the interactions between the environment and the genetic blueprint. While current concepts generally view global deteriorations of epigenetic marks to insidiously impair cellular and molecular functions, an active role for epigenetic changes in aging has so far received little attention.

In this regard, we have recently shown that early-life adversity induced specific changes in DNA methylation that were protected from an age-associated erasure and correlated with a phenotype well-known to increase the risk for age-related mental disorders. This finding strengthens the idea that DNA (de-)methylation is controlled by multiple mechanisms that might fulfill different, and partly contrasting, roles in the aging process.

Age-associated epigenetic modifications in human DNA increase its immunogenicity

Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells.

...

Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer.

In the context of that second paper, you might firstly look at a recent post on age-related damage to the innate immune system. Very little if anything in our biochemistry changes in isolation. Secondly, you should wander back into the Fight Aging! archives for a refresher on why chronic inflammation in aging is such a bad thing:

• Inflammation and the Damage of Aging
• Avoid Chronic Inflammation
• A Novel View of Inflammaging

Murgatroyd C, Wu Y, Bockmühl Y, & Spengler D (2010). The Janus face of DNA methylation in aging. Aging, 2 (2), 107-10 PMID: 20354272

Cytomegalovirus (CMV) is one of the reasons our immune systems decay with aging: too many immune cells become specialized to deal with CMV, leaving too few to deal with everything else. New research "explains how a virus that has already infected up to 80 percent of the American population can repeatedly re-infect individuals despite the presence of a strong and long-lasting immune response. The research involves cytomegalovirus (CMV), which infects 50 percent to 80 percent of the U.S. population before age 40. ... For most people, CMV infection goes undetected and they do not become seriously ill. ... When most viruses infect a host, the immune system remembers the disease and protects against re-infection. This is the case with smallpox, seasonal strains of flu and several other viruses. This immune system reaction is also the reason why vaccines made with weakened or dead viruses work against these pathogens. In the case of CMV, the body's immune system is continuously stimulated by ongoing, low-level persistent infection, but yet CMV is still able to re-infect. This research explains how CMV is able to overcome this immune response so that re-infection occurs. ... The results of this study primarily illustrate the significant barriers to creating a vaccine that will prevent CMV infection." But a vaccine won't do much for people already burdened by an CMV-focused immune system. What we want is a way to use targeted cell killing strategies to destroy CMV-related immune cells and free up space for more useful immune cells.

Link: http://www.eurekalert.org/pub_releases/2010-04/ohs-ore033010.php

Rapamycin recently showed promise as a potential treatment for Alzheimer's disease, and here more researchers are working on that: "A few weeks after a report that rapamycin, a drug that extends lifespan in mice and that is currently used in transplant patients, curbed the effects of Alzheimer's disease in mice, a second group is announcing similar results in an entirely different mouse model of early Alzheimer's. ... The second report [showed] that administration of rapamycin improved learning and memory in a strain of mice engineered to develop Alzheimer's. The improvements in learning and memory were detected in a water maze activity test that is designed to measure learning and spatial memory. The improvements in learning and memory correlated with lower damage in brain tissue. ... Strikingly, the Alzheimer's mice treated with rapamycin displayed improved performance on the maze, even reaching levels that were indistinguishable from their normal littermates. Levels of amyloid-beta-42 were also reduced in these mice after treatment, and we are seeing preserved numbers of synaptic elements in the brain areas of Alzheimer's disease mice that are ravaged by the disease process."

Link: http://www.eurekalert.org/pub_releases/2010-04/uoth-adt040110.php

An article from the Duke University media outlet reminds us of the bigger historical picture of human life expectancy: continual incremental improvement ever since the Industrial Revolution. It's also a good example of how to write a decent popular science press piece, one that adds context to the research it references, rather than dumbing it down or papering it over. From the perspective of the reliability theory of aging and longevity, the historical increase in life expectancy has occurred because better and more widespread availability of medical technology lowers the rate at which biological damage accumulates. Prevention of chronic infectious disease, for example, falls into this category: disease applies a damage load to an individual, and that damage reduces the mean time to failure of bodily systems.

"We're living longer because people are reaching old age in better health," said demographer James Vaupel, author of a review article appearing in the March 25 edition of Nature. But once it starts, the process of aging itself - including dementia and heart disease - is still happening at pretty much the same rate. "Deterioration, instead of being stretched out, is being postponed." ... Over the past 170 years, in the countries with the highest life expectancies, the average life span has grown at a rate of 2.5 years per decade, or about 6 hours per day.

Six hours per day sounds a lot more exciting than a few years per decade - there's a lesson about the time preference of human psychology lurking in there somewhere. Advocates take note: tell your friends how many extra hours of life they gained today thanks to advancing medical technology, and see what they say.

But to return to the article, the other lesson here is that changing longevity changes human society - entirely for the better so far. The effect is somewhat delayed in modern times, as people look to their parents for the course of their own life - which is not going to help much in today's world of accelerating biotechnology. We will have access to technologies of engineered longevity that weren't even science fiction twenty years ago. But people are structuring their lives differently to those of their grandparents precisely because they expect to live noticeably longer:

It also may be time to rethink how we structure our lives, Vaupel said. "If young people realize they might live past 100 and be in good shape to 90 or 95, it might make more sense to mix education, work and child-rearing across more years of life instead of devoting the first two decades exclusively to education, the next three or four decades to career and parenting, and the last four solely to leisure."

One way to change life trajectories would be to allow younger people to work fewer hours, in exchange for staying in the workforce to a later age. "The 20th century was a century of the redistribution of wealth; the 21st century will probably be a century of the redistribution of work," Vaupel said.

I've looked at this topic numerous times in the past; you might dig back into the archives and take a look at these posts, for example:

• The Transformation of Retirement
• Wealth and Longevity
• Longevity Tends to Change Economic Behavior For the Better
• Pondering the Nature of an Ageless Society
• Changing Human Life Span Means Changing Human Society - For the Better

One last note: that we can talk about "allowing" people to work in the context of what government bureaucrats in many regions write into law and enforce by threat of jail - mandatory retirement, for example - is a great iniquity. It is vile that one group of privileged people force their way into the private contracts of others:

• Work, Retirement and the Times They Are A-Changing
• A Future in Which You Won't Be Forced to Retire
• The Iniquity of Enforced Retirement

Retirement forced on people who are perfectly capable and willing to work is a terrible thing. Only in a dreadfully twisted social environment can more willing workers be transformed from boon into problem. Sadly, most of us live in just such a society, repleat with forced wealth transfers, counterproductive medical regulations, and the tragedy of the commons writ large upon taxed wealth and shoddy government monopoly services. This is what happens when socialist ideas prosper.

Vaupel, J. (2010). Biodemography of human ageing Nature, 464 (7288), 536-542 DOI: 10.1038/nature08984

The DAF-16 gene in nematode worms such as C. elegans is thought to be the fulcrum of a metabolic feedback loop that switches between long-lived stress resistant and short-lived reproduction focused states. "Ageing is a process that all organisms experience, but at very different rates. We know that, even between closely related species, average lifespans can vary enormously. We wanted to find out how normal ageing is being governed by genes and what effect these genes have on other traits, such as immunity. To do that, we looked at a gene that we already knew to be involved in the ageing process, called DAF-16, to see how it may determine the different rates of ageing in different species. ... Researchers compared longevity, stress resistance and immunity in four related species of worm. ... They also looked for differences in the activity of DAF-16 in each of the four species and found that they were all quite distinct in this respect. And, importantly, the differences in DAF-16 corresponded to differences in longevity, stress resistance and immunity between the four species - in general higher levels of DAF-16 activity correlated with longer life, increased stress resistance and better immunity against some infections."

Link: http://www.bbsrc.ac.uk/media/releases/2010/100401-ageing-gene-found-to-govern-lifespan.aspx

One day, it will be possible to replace nerves with entirely artificial conduits. This is a branch of medical technology that will compete with regenerative medicine, and ultimately lead to more effective and resilient body parts. But today, the foundations are still being designed. A long road lies ahead. Here, the New Scientist looks at early work: "Schiefer is describing an experiment in which pulses of electricity are used to control the muscles of an unconscious patient, as if they were a marionette. It represents the beginnings of a new generation of devices that he hopes will allow people with paralysed legs to regain control of their muscles and so be able to stand, or even walk again. His is one of a raft of gadgets being developed that plug into the network of nerves that normally relay commands from the spinal cord to the muscles, but fall silent when a spinal injury breaks the chain. New ways to connect wires to nerves [allow] artificial messages to be injected to selectively control muscles just as if the signal had originated in the brain. Limbs that might otherwise never again be controlled by their owners can be brought back to life. ... Nerves contain tens of thousands of axons, each capable of being controlled by the ultimate puppeteer: the brain. Learning to pull even a few of those strings, though, could restore partial function to a person's limb, restoring some control to an arm or leg that was previously paralysed."

Link: http://www.newscientist.com/article/mg20627546.200-paralysed-limbs-revived-by-hacking-into-nerves.html?full=true

At the Maximum Life Foundation blog: "Since the Industrial Revolution, alarmists screamed doom and gloom about overcrowding and limited resources (backed by their "statistics"). However, the opposite has happened. The population increased by 740% since then, and standards of living have soared. It's not so much a question of resources as it is one of education, individual productivity and distribution—social problems, not life-extension problems. As long as people produce more than they consume, it's impossible to run out of resources. Common sense and intuition say there should be a demographic catastrophe, if people were actually immortal and continued to reproduce. But what would the science (mathematics) say? Recently, Drs. Leonid and Natalia Gavrilov answered that question with a study sponsored by the SENS/Methuselah Foundation. They proved it is possible to have sustainable population dynamics in a future hypothetical non-aging society. ... A general conclusion of this study is that population changes are surprisingly small and slow in their response to dramatic life extension. Even in the case of the most radical life extension scenario, population growth could be relatively slow and may not necessarily lead to overpopulation. Therefore, the real concerns should be placed not on the threat of overpopulation, but rather on such potential obstacles to a successful biomedical war on aging, such as scientific, organizational and financial limitations."

Link: http://maxlifefoundation.typepad.com/maximum-life-foundation/2010/03/david-kekich-why-overpopulation-will-never-be-a-problem.html

From ScienceDaily: researchers "used a non-viral, synthetic nanoparticle carrier to improve and save the sight of mice with retinitis pigmentosa, an inherited disease characterized by progressive vision loss and eventual blindness. ... [Researchers] used groups of mice with the retinal degeneration slow (Rds) gene, which causes retinitis pigmentosa. The mice received one of three types of 'treatments:' nanoparticles containing the normal copy of the Rds gene, the normal gene alone, or saline solution. After these treatments were delivered to the mice, the structure and function of the retina were analyzed by comparing them to untreated mice with retinitis pigmentosa and healthy mice with the normal Rds gene. Researchers also measured the level and pattern of Rds gene expression, as well as functional, structural and biochemical improvements in disease symptoms. They discovered that mice receiving the nanoparticle gene therapy show significant signs of healing. These mice had structural improvement in their retinas, as well as functional vision improvements, which lasted throughout the duration of the study. The mice that received the gene alone or saline continued to lose their vision. The nanoparticles were safe and well-tolerated with no adverse effects."

Link: http://www.sciencedaily.com/releases/2010/03/100331141623.htm

If you head over to the Methuselah Foundation or Mprize, you'll see that a new research prize has been announced:

In April 2010 Methuselah Foundation challenges researchers: Find the solution to organ failure. We seek, support and reward science that extends healthy lifespan. And we believe a permanent solution to organ failure can be found. That's why we are announcing two initiatives:

1) NewOrgan Prize: Prizes result in amazing leaps forward in science; we challenge scientists to construct and successfully transplant a whole new organ made from a patient's own cells by 2020.

2) NewOrgan Network: A social community, powered by our partner My Bridge 4 Life, where those in need of replacement organs can reach out to friends and family for personal support.

This follows on from the recently announced funding for a NewOrgan registry, and shows that the Foundation leadership are very interested in establishing their presence and making a difference in the field of tissue engineering and organ regrowth:

Most people live in the here and now: it's hard to persuade them that the future will be far different from what they see today. Yet these folk make up the majority of the population, and until we can persuade them to see things our way, the quest to extend the healthy human life span will remain a fringe interest. We need the enthusiasm and help of the masses to support the pace and breadth of progress we'd like to see.

One of the ways in which the Methuselah Foundation is approaching this problem is funding for cutting edge regenerative medicine, such as organ growth. These are more widely supported and understood technologies, and making the Foundation a player in this space will help to put the message of engineered longevity in front of more people, and in a way they are more likely to sympathize with and understand.

Research prizes work well, and the NewOrgan Prize should help to bring forward the day on which a heart or other vital organ can be built from scratch, from your own cells, and provided as a replacement for an age-damaged organ.