Fight Aging!

Here and there, I'll post on the topic of cryonics, economics (in the broadest sense of the term) and the presently very restrictive legal frameworks surrounding death. Cryonics is the low-temperature storage of the brain, and usually the rest of the body as well, preserving the data encoded in the fine structure of the tissue. In the future, advanced and foreseeable technology will make it possible to restore to life these cryopreserved people. The physics of it all is comparatively settled in comparison to the uncertainties introduced by human nature and human society, however.

A brief summary of the points I've discussed in the past are as follows:

• You don't have to be wealthy to afford cryopreservation. Most people who are preserved are of modest means and funded their procedure and storage through life insurance.
• The economics of being effectively dead are fairly dire. There are no successful examples of people managing long-term direction of their finances when they are personally removed from the picture - the incentives of all other parties are lined up against you. So don't expect take any of your wealth with you. But so what? You were alive and poor once already, and doing that again won't hurt in comparison to the alternative.
• The present legalities of death and personal autonomy are not what they might be, and the cryonics industry is consequently very interested in the right to self-determination. The employees of most first world legal systems will do all they can to ensure that you cannot decide the time of your own death; it therefore becomes far, far harder to perform a good cryopreservation. The process cannot be organized to a timetable, and becomes far more costly and uncertain. Just how free are you when your government claims it controls you to such a degree that you cannot even die on your own terms?
• Similarly, your relatives are often your worst enemies when it comes to a good cryopreservation. Whatever they say to your face, if their incentives do not align with yours, then they will fight to claim the funds that would have preserved you and cheerfully consign you to the grave and certain oblivion. In this they are supported by law and a legal system that will frequently prioritize their unreasonable claims over the contracts you thoughtfully signed.
• Atop of all of this, there is a certain tendency amongst enthusiasts for freedom - as well as other folk - to take written words on paper at their face value. To believe that contracts can determine the acts of men and women, in other words, even when those acts are at odds to their incentives. Sadly the world doesn't work that way; words on paper, like all promises, are worthless when one of the signing sides has no incentive to abide by them.

My bias in these matters is no doubt well know to readers here: government employees are not your friends, and the law is a beast that looks only to its own perpetuation. A free society would not suffer the indignities forced upon so many people by "public servants." But we do not live in a free society, and I imagine that wealthy free societies will not arise in our era - at least not until commercial spaceflight advances sufficiently to open the next great frontier.

So to the point of the post: my attention was recently directed to an open paper on law and cryopreservation. It was written by a student of law, so while recognizing the issue at hand, the solution proposed is made up of what are effectively more legal undertakings, just at a legislative level - which I fear rather misses the true source of the problem. Beyond that, the article provides a good review of the past and legal present of the cryonics industry, and is very educational in that respect. For example, the following quote references one of the more outrageous cases in recent history:

In 1988, doctors diagnosed Thomas Donaldson with an incurable brain tumor. The tumor was in a region of the brain that does not affect thinking, but rather physical coordination. In 1990, Donaldson, an Alcor member, decided to file a lawsuit to force the state to allow his pre-mortem cryonic preservation. Donaldson sought a judicial declaration that he "has a constitutional right to premortem cryogenic suspension of his body and the assistance of others in achieving that state." As the court boldly framed the issue, "Plaintiff Thomas Donaldson wishes to die in order to live."

...

The court stated: "The state may also decline to assess the quality of a particular human life and assert an unqualified general interest in the preservation of human life to be balanced against the individual's constitutional rights." After weighing these state interests against Donaldson's assertion of a constitutional right to cryonic suspension, the court concluded that it is "unfortunate for Donaldson that the courts cannot always accommodate the special needs of an individual."

A man whose brain was being destroyed by cancer was told he could not arrange the best shot at a chance to preserve his mind and self - and that the law will punish him and all who help him if he tries. If you value self-determination and the rights of the individual then this sort of thing should make your blood boil. Are we serfs and subjects, to be treated like cattle, and our lives sacrificed to laws that serve no purpose beyond their own continuance? Clearly much of the government apparatus in the US is built upon the belief that the answer to that question is "yes."

A long post from earlier this month at Chronosphere examines technological inevitability - or rather what seems to be its absence if you look back at history. The post is in the context of science and development in cryonics, but the general theme applies just as much to the technologies of enhanced human longevity: just because we are entering an age in which it is possible doesn't mean that it will happen. "One of the most fundamental insights I've ever had came when I was in Rome, and also reading a very good biography of Leonardo da Vinci, in preparation for a visit to Florence. Da Vinci spent most of his career designing war machines, and trying to reroute the Arno River for military advantage. As I looked at the remains of the awesome Ancient Roman engineering around me, and thought of da Vinci, it occurred to me that one of the most powerful and off putting military advantages that could have been deployed, in either Ancient, or Renaissance times, would have been hot air balloons. ... Lighter than air craft are very easy to build, and both the Ancient Romans and the Renaissance Italians had the materials, the wealth, and the technology. The Colosseum was covered with canvas awnings, the Velarium, that were operated by a complex series of ropes and pulleys, and the Romans were superb canvas makers and produced the material in copious amounts to use for ships' sails. Why didn't they develop lighter than air flight - and why didn't Leonardo?" It is not inevitable that we will develop true rejuvenation biotechnology soon enough to save us from aging to death: the only way this will happen is if we make it happen, through activism, education, fundraising, and the other traditional methods of changing the path taken by our society. Sitting back, doing nothing, and assuming we're going to be rescued is the road to suffering and death.

Link: http://chronopause.com/index.php/2011/02/07/67/

Obtaining 501(c)(3) tax exempt status in the US is an ordeal, and one that the SENS Foundation has now completed: "SENS Foundation is pleased to announce that it has been granted tax-exempt status as a 501(c)(3) public charity, with an effective date of March 9, 2009. Donations to the Foundation are fully deductible as a charitable contribution." If you've been putting off donating to support the SENS Foundation's work on the development of rejuvenation biotechnology, now is an excellent time to jump on in. Research costs money, but in the grand scheme of things the cost of building the first generation of technologies that will enable us to live for decades longer - and thus gain the time to wait for the second generation that will be even more impressive - is small. It will take only a few tens of millions of dollars a year for each of the strands of the Strategies for Engineered Negligible Senescence. That is a rounding error when compared against either the total medical funding in the US, or total charitable donations in the US. So make a donation, and persuade a few other people to look into the work of the SENS Foundation.

Link: http://sens.org/node/1935

Great inroads have been made in recent years into an understanding of the accelerated aging condition called Hutchinson-Gilford progeria syndrome, or progeria. Despite its extreme rarity - there are less than a hundred sufferers known worldwide - the condition is of great interest to aging researchers, and this is because of what progeria might teach us about a range of important cellular mechanisms and their impact on "normal" aging.

The breakthrough discovery linking progeria with malformed lamin A protein back in 2003 came about as a result of advances in biotechnology. Thanks to rapid technological progress, the means to make this discovery became cheap enough that one determined researcher could push through to succeed in a comparatively short time frame. Ten years previously, that would have been impossible for such a small research effort.

Today the tools of cellular biotechnology are at least as far advanced over the state of the art in 2003 as that year was over the early 1990s. As a result new avenues are opening up in the investigation of progeria's mechanisms - and their relevance to the rest of us. A recent research release from EurekAlert!, for example, shows how application of the comparatively recent technologies of induced pluripotency (used to produce induced pluripotent stem cells, or iPS cells) are leading to further discoveries in both aberrant and "normal" aging:

Hutchinson-Gilford Progeria Syndrome is caused by a single point mutation in the gene encoding lamin A, which forms a protein scaffold on the inner edge of the nucleus that helps maintain chromatin structure and organize nuclear processes such as RNA and DNA synthesis. The mutation creates an alternative splice site that leads to the production of a truncated version of the protein known as progerin. Unlike the full-length protein, progerin does not properly integrate into the nuclear lamina, which disrupts the nuclear scaffold and causes a host of problems.

"There is also evidence that defective lamin A accumulates during the normal aging process via the sporadic use of the alternative splice [site]. Therefore we are very keen [to] identify new aging markers and explore other aspects of human premature and physiological aging."

...

Compared to normal skin fibroblasts, cells from Progeria patients have misshapen nuclei and a range of other nuclear defects, including a disorganized nuclear lamina, loss of super-condensed DNA, telomere shortening and genomic instability. Yet, despite their "old" appearance and characteristics, these cells could be readily converted into iPS cells.

"The reprogramming process erased all nuclear and epigenetic defects and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells."

Which is a very interesting result. You might compare it with another demonstration made recently in which damaged cells lost their damaged status when altered to become induced pluripotent stem cells. Unlike that case, however, here the induced pluripotent cells still bear the seeds of the damage: when they differentiate into other types of cell, those cells once again produce the bad lamin A and suffer the characteristic effects of progeria.

The researchers conclude that a therapy might be built through genetic manipulation and cell transplant, as they were able to fix the differentiated cells via that approach:

Genetically modifying progeria-derived iPS cells to shut down the expression of progerin staved off the premature appearance of aging phenotypes after differentiation. "Transplantation of the progenitor cells derived from the 'corrected' progeria iPS cells might hold the promise to treat these progeria children in the future."

As I have noted in the past, a comprehensive fix for progeria may well be of some benefit to those of us suffering "normal" aging as well.

Can improving the technologies of vaccination lead to gains in the capacity of the age-damaged immune system? Progress in the ability to manipulate the immune system may pay off in unexpected ways when further technologies are built atop a new platform: "Vaccine scientists say their 'Holy Grail' is to stimulate immunity that lasts for a lifetime. Live viral vaccines such as the smallpox or yellow fever vaccines provide immune protection that lasts several decades, but despite their success, scientists have remained in the dark as to how they induce such long lasting immunity. Scientists [have] designed tiny nanoparticles that resemble viruses in size and immunological composition and that induce lifelong immunity in mice. They designed the particles to mimic the immune‑stimulating effects of one of the most successful vaccines ever developed - the yellow fever vaccine. The particles, made of biodegradable polymers, have components that activate two different parts of the innate immune system and can be used interchangeably with material from many different bacteria or viruses. ... the yellow fever vaccine stimulated multiple Toll‑like receptors (TLRs) in the innate immune system. TLRs [are] molecules expressed by cells that can sense bits of viruses, bacteria and parasites ... the immune system sensed the yellow fever vaccine via multiple TLRs, and that this was required for the immunity induced by the vaccine. ... We found that to get the best immune response, you need to hit more than one kind of Toll‑like receptor. Our aim was to create a synthetic particle that accomplishes this task. ... In experiments with monkeys, nanoparticles with viral protein could induce robust responses greater than five times the response induced by a dose of the same viral protein given by itself, without the nanoparticles."

Link: http://www.kurzweilai.net/virus-mimicking-nanoparticles-can-stimulate-long-lasting-immunity

Young mammals are capable of feats of regeneration: even in humans, it has been known for young children to regenerate lost fingertips. That capacity fades with age, however. Researchers are investigating the biochemistry of this behavior for much the same reasons as they look at regenerating species such as salamanders - if the capacity is there, perhaps it can be restored in adults. "Researchers, working with mice, found that a portion of the heart removed during the first week after birth grew back wholly and correctly - as if nothing had happened. ... This is an important step in our search for a cure for heart disease, the No. 1 killer in the developed world. We found that the heart of newborn mammals can fix itself; it just forgets how as it gets older. The challenge now is to find a way to remind the adult heart how to fix itself again. ... Previous research has demonstrated that the lower organisms, like some fish and amphibians, that can regrow fins and tails, can also regrow portions of their hearts after injury. ... In contrast, the hearts of adult mammals lack the ability to regrow lost or damaged tissue, and as a result, when the heart is injured, for example after a heart attack, it gets weaker, which eventually leads to heart failure. ... The researchers found that within three weeks of removing 15 percent of the newborn mouse heart, the heart was able to completely grow back the lost tissue, and as a result looked and functioned just like a normal heart. The researchers believe that uninjured beating heart cells, called cardiomyocytes, are a major source of the new cells. They stop beating long enough to divide and provide the heart with fresh cardiomyocytes."

Link: http://www.eurekalert.org/pub_releases/2011-02/usmc-nhm022311.php

A little while back, I was invited to preview an independent project under development at the behest of Alex Zhavoronkov, one of the trustees of the UK-based Biogerontology Research Foundation, a group with strong ties to the Methuselah Foundation and SENS Foundation communities. That project is now launched and open to the world: it is the International Aging Research Portfolio - "tracking international progress in aging research".

The site grants users access to research and funding information for over a million [projects]. The IARP is a fully searchable, flexible and highly scalable knowledge-management system developed to enable organizations to collaborate, track, analyze, structure, make decisions and set directions for future research efforts in aging. ... Aging research spans many areas of natural and social and behavioural sciences and requires a high degree of interdisciplinary and international cooperation. The goal of IARP is to provide a centralized decision support system for scientists, research institutes, funding organizations and policy makers involved in aging research.

If you are a statistics addict, this might keep you occupied for a while. The aggregated funding data and trends in research are particularly interesting, and could be more so if further sliced and diced. For example, funding by theory of aging:

Color me surprised that funding of work on telomeres in aging is so very far ahead - but there's the purpose of data mining, to learn. The hope here is that data mining tools that operate on this large data set will provide compelling benefits for the research community, such as by making it easier to match up research proposals to funding sources based on the sort of awards made in the past.

Public sources of funds are over-represented in this database by virtue of being public sources and thus producing records that are generally more accessible. One can imagine a slow extension of such a data aggregation operation into the private funding space based on the same provision of compelling benefits. If you make it worthwhile by streamlining the process of fundraising (on the research side) and the process of finding suitable projects to fund (on the funding source side), then people will use the system and in the process support its evolution and growth.

We expect to see good correlations between many aspects of our biology and aging: "Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age." Equally, it may go the other way - these changes could just as well be the symptoms of damaged systems flailing as they try to adapt to countless small breakages at the level of cells and molecular machinery. It is important in the development of therapies for aging to try to identify the root causes, as fixing those will also solve secondary issues.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21336567

Decellularization is proving to be a versatile technology in tissue engineering: grow the tissue from stem cells or accept a donor organ, strip its cells to leave behind the extracellular matrix, and then repopulate it from the recipient's stem cells to make it ready for transplant. For example: "Heart bypass patients may soon be able to get new arteries without having to sacrifice vessels from other parts of their body, thanks to ready-made, off-the-shelf artificial blood vessels. Biomedical engineers have been trying to build replacement blood vessels, needed for coronary artery bypass surgery and kidney dialysis patients, for three decades. Researchers from Humacyte Inc., in Durham, N.C., discovered the trick: recruiting cells to build the vessel, then washing them away so the nonliving tissue is storable and works for anyone. ... The company has managed to make a "universal blood vessel. This is very practical and convenient for clinical applications. ... Other approaches, customized with a patient's own cells, take several months to prepare. ... Though Humacyte is starting to plan human clinical trials, it's too early to predict when the grafts would become available to the general public. ... [researchers] not yet know how much the grafts would cost, but anticipates it will be less than the $15,000-and-up for personalized grafts from patient's own cells. The company can use cells from multiple cadavers to generate hundreds of grafts at once, making production much cheaper."

Link: http://www.latimes.com/health/la-he-blood-vessels-20110221,0,6930611.story

I am not complacent about the cancers that no doubt lie in my future - just as they lie in yours. But I am not terribly concerned either; I give more thought to the fate of my wallet than to the fate of my flesh when it comes to cancer. By the time I hit the stage of life at which cancers are most likely to manifest, then the state of the art in safe and robustly effective cancer therapies will be impressive indeed. That will be true even if all that happens in between now and then is that the present technology demonstrations carried out in laboratories are developed into commercially available therapies ... and I'd expect far more progress than that to happen over a twenty year span of time.

Here are two more reassuring examples of ongoing development in biotechnology for those of us fortunately enough to have the luxury of time when it comes to cancer - even if we certainly don't have the luxury of time when it comes to aging itself.

Nanotechnology may lead to new treatment of liver cancer:

Researchers evaluated the use of molecular-sized bubbles filled with C6-ceramide, called cerasomes, as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell's plasma membrane and controls cell functions, including cell aging, or senescence. ... The beauty of ceramide is that it is non-toxic to normal cells, putting them to sleep, while selectively killing cancer cells

...

Cerasomes [can] target cancer cells very specifically and accurately, rather than affecting a larger area that includes healthy cells. The problem with ceramide is that as a lipid, it cannot be delivered effectively as a drug. To solve this limitation, the researchers use nanotechnology, creating the tiny cerasome, to turn the insoluble lipid into a soluble treatment.

...

Researchers [previously] observed that cerasome use led to complete remission in aggressive, large granular lymphocytic leukemia in rats. ... It is plausible that preventing liver tumor vascularization with cerasome treatment could induce widespread apoptosis, a genetically programmed series of events that leads to cell death in tumors

The Answer To Wiping Out Cancer Could Be World's First Chemical Guided Missile:

Current cancer treatments destroy the cells that form the bulk of the tumour, but are largely ineffective against the root of the cancer, the cancer stem cells. This suggests that in order to provide a cure for cancer we must accurately detect and eliminate the cancer stem cells.

...

researchers have [created a targeted] RNA aptamer, a chemical antibody that acts like a guided missile to seek out and bind only to cancer stem cells. The aptamer has the potential to deliver drugs directly to the stem cells (the root of cancer cells) and also to be used to develop a more effective cancer imaging system for early detection of the disease.

Many different research groups are developing many different competing methods of both targeting cancer cells and delivering existing chemotherapy compounds in a highly targeted way. The chemical compounds used in many existing cancer therapies could be the basis for very safe and very effective future therapies if only they could be delivered just to cancer cells, and in small doses that did not leak out into neighboring tissues. This is exactly the capability being demonstrated over the past few years in laboratories around the world.

Researchers demonstrate that exercise can counter some of the effects of an engineered acceleration of mitochondrial dysfunction: "researchers [found] that signs of premature aging were halted - and even reversed - in virtually every tissue and organ in the bodies of exercised mice. Mice genetically altered to age faster were forced to run on treadmills for 45 minutes, three times a week. Five months later, the mice looked as young, healthy and active as wild-type mice - mice that didn't have the genetic mutation - while their sedentary and same-aged siblings were balding, greying and shrinking. .. The mice were genetically manipulated to age twice as fast as normal because of a defect in the repair system of their mitochondria, the powerhouses or furnaces inside each cell that give our body energy. Evidence has been mounting for decades that the older we get, the more mutations we accumulate in mitochondrial DNA. The furnaces start to break down, resulting in a steady decline in tissue and organ function. ... In our study, we saw huge recovery in mitochondrial function [in] the exercised mice." We might expect this result, given that exercise is known to have an impact on longevity, as well as on many of the biological mechanisms that are associated with aging. Given the importance of mitochondria in aging, it is interesting to see more work on the links between exercise and their function - but we must always be careful when evaluating work based on engineered dysfunction or accelerated aging. It is often the case that the putative end result has little relevance to "normal" aging.

Link: http://www.vancouversun.com/health/health/4321105/story.html

An open access paper: "Nearly 50 years ago geneticist James Neel famously proposed that 'thrifty genes' were important contributors to the rising prevalence of diabetes. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come. ... Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. ... I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging, this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways - notably those involving mTOR, insulin, and insulin-like growth factor-1 - that support rapid development and sexual maturation but that also underlie later senescence. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth."

Link: http://www.impactaging.com/papers/v3/n2/full/100286.html

Follow the links below for a little photography for an otherwise slow Tuesday:

My Visit to KrioRus - the First Cryonics Company in Europe and Asia

Yesterday I visited the facilities of the Russian cryonics company KrioRus, which are located just outside Moscow. That's the huge dewar flask where the cryopreserved bodies are stored. It's so big that one needs to climb up a ladder to peek through the steamy nitrogen. And in the picture below Alexei Turchin, a renowned futurologist and expert on global risks, and I are in front of the other dewar flask, now empty and waiting for the new cryo patients. Cryonics is an amazing opportunity to get a chance to find yourself in the future. I believe cryonics is the choice of truly smart people.

SENS Foundation 'Lab Warming'

One of the Foundation's achievements last year was our Research Center's moving to a larger laboratory space, in Mountain View, California. Earlier this month we held a small opening event. It gave us a chance to thank our Research Operations Manager, Tanya Jones, and her team, for all their work in yet-again increasing the capabilities of the Foundation to pursue its core research interests. Anyway ... I took some snapshots during the afternoon, and thought I'd share them.

KrioRus and the SENS Foundation are two amongst a wide range of modern ventures in longevity science - although very different in focus, both are just a few years old and spring from overlapping communities of supporters, most of whom have been involved in the space for a decade or two at most. The longevity advocacy and interest community has a much longer history, and has become generational in nature over time. The folk who were most active in the early 90s are largely not the folk who are most active now, and progress in the form of new initiatives and public interest tends to arrive in waves. This I see as a good thing: life is change, and all broad movements need the influx of new faces and new movers and shakers in order to progress.

The Cryonics magazine published by Alcor is looking very professionally done these days. If you head on over there, you'll find a good-looking website and crisp PDF downloads: "Cryonics magazine is the quarterly electronic publication of the Alcor Life Extension Foundation. Cryonics magazine is also available as a paper magazine by ordering individual copies at MagCloud or by ordering subscriptions to the paper edition from Alcor. The magazine website also publishes exclusive content and news items that are relevant to the science and practice of cryonics. ...The 2010 4th quarter issue of Cryonics covers the challenging and sensitive topic of persuading family members to make cryonics arrangements. Editor Aschwin de Wolf contributes an article about writing cryonics case reports and how to overcome the challenges that a growing cryonics organization presents for writing them. We continue our coverage of Alcor staff members with a feature on Alcor Finance Director Bonnie Magee. ... The 2010 3rd quarter issue of Cryonics publishes the first comprehensive Alcor Human Cryopreservation Protocol. This document covers all steps of cryonics procedures, from standby to long term care at liquid nitrogen temperatures. Robert Freitas summarizes his econometric analysis of Alcor finances and Alcor staff member and life extension historian Mike Perry is featured in this issue's member profile."

Link: http://www.alcor.org/magazine/

From CNN: "We started out by taking a typical desktop inkjet cartridge. Instead of ink we use cells, which are placed in the cartridge ... The device could be used to rebuild damaged or burned skin. The project is in pre-clinical phases and may take another five years of development before it is ready to be used on human burn victims. ... researchers say organs - not just skin - could be printed using similar techniques. ... The skin-printing process involves several steps. First, a small piece of skin is taken from the patient. The sample is about half the size of a postage stamp, and it is taken from the patient by using a chemical solution. Those cells are then separated and replicated on their own in a specialized environment that catalyzes this cell development. ... We expand the cells in large quantities. Once we make those new cells, the next step is to put the cells in the printer, on a cartridge, and print on the patient ...The printer is then placed over the wound at a distance so that it doesn't touch the burn victim. ... It's like a flat-bed scanner that moves back and forth and put cells on you. ... The device can fabricate healthy skin in anywhere from minutes to a few hours, depending on the size and type of burn. ... researchers said they're pleased with results of preliminary laboratory testing with the skin printer [and] already have been able to [make] healthy skin."

Link: http://www.cnn.com/2011/TECH/innovation/02/19/bioprinting.wounded.soldiers/index.html

There is a very simple measure for any new potential therapy for enhanced longevity: is it either (a) doing at least as well as calorie restriction in mice when it comes to health and longevity, or (b) achieving important results that calorie restriction cannot show in mice - such as outright rejuvenation. The popular supplement resveratrol fails miserably to achieve significant results in either of these goals after more than five years of experimentation and hundreds of millions of dollars in research funding. This means that it is a dead end, or so close to one as makes no real difference. The only value gained lies in incremental improvements in the understanding of metabolism - which could have been achieved while studying more effective paths to the same end goal.

Resveratrol and life extension

Age is the most important risk factor for diseases affecting the Western world, and slowing age-related degeneration would greatly improve the quality of human life. In rodents, caloric restriction (CR) extends lifespan by up to 50%. However, attempts to mimic the effects of CR pharmacologically have been limited by our poor understanding of the mechanisms involved. SIRT1 is proposed to mediate key aspects of CR, and small molecule activators may therefore act as CR mimetics.

The polyphenol resveratrol activates SIRT1 in an in vitro assay, and produces changes that resemble CR in vivo, including improvements in insulin sensitivity, endurance, and overall survival in obese mice. However, resveratrol has numerous other targets that could contribute to its health benefits. Moreover, unlike bona fide CR, resveratrol has not been shown to extend lifespan in lean mice.

Whenever a new supplement, drug, or something else you can put in your mouth is announced to possibly affect longevity, there follows a breathless wave of hype and money-making. Go search for "resveratrol" to see the present pointless wasteland of thoughtless buyers and manipulative sellers. You'd think that no-one has a memory of longer than a year: every time this happens exactly the same way, and in the end it all comes to nothing.

Silver bullets don't exist, and the future of longevity science will not be found in paths that fail to show immediate, exciting benefit in mouse studies. When there are multiple ways to extend mouse life span by 50%, why would anyone be worked up about about something that fails to move the needle at all? It's way past time to move on from the resveratrols of the world and focus on research and development that can have a positive effect on the future of human longevity.

There is a debate over whether aging is a disease, and here is some insight into where the aging of the brain and neurodegenerative diseases fit into that larger argument: the "question of whether 'aging itself' is or is not a 'disease' has long been mooted in biogerontological circles, with a long-held rhetorical preference for asserting that it is not, but rather, that it is a risk factor for the specific diseases of aging. By contrast, the same fundamental semantic dispute was initially resolved in the opposite direction with regard to age-related cognitive decline and dementia, beginning in the early decades after Alois Alzheimer and Emil Kraepelin first identified the pathological basis of the Alzheimer's disease (AD) until the early 1970s. For most of the twentieth century, it was held that dementia occurring in younger people should be classified as a disease, whereas dementia should be expected and accepted when it occurred in people at more advanced ages, despite the knowledge that the lesions linked to Alzheimer's dementia accumulated throughout the course of "normal" aging in middle age and onward, and that the pathological basis of the disorder was the same in both cases. ... But beginning in the 1960s, a loose alliance led by social gerontologists but quickly coming to include biogerontologists, geriatricians, and patient advocacy groups successfully campaigned for a new understanding: that while some level of minor cognitive decline was indeed a 'normal' and inevitable part of aging, the newly-rediscovered clinicopathological entity, 'Alzheimer's disease,' was exactly that: a disease, against which the full force of public and private biomedical research should be mobilized in the pursuit of a cure." These debates are almost entirely driven by the state of regulation in medical development; in particular that the FDA does not approve treatments that are not aimed at a defined and accepted disease - and aging is not a disease to the regulators, so no-one can try to treat it legally. This is an abysmally stupid situation, but sadly par for the course wherever government becomes involved.

Link: http://sens.org/node/1919

An interesting piece on the comparison of aging between species: "The 'shape' of aging describes how much mortality, the risk of dying, changes with age. One way of measuring the shape of aging is the 'aging factor' across species. For example, the common swift has an aging factor of 2, meaning mortality doubles during its adult life, compared with modern humans, who have an aging factor that exceeds 2000. ... Some organisms live a short time, others live a long time. This is the pace of ageing. Short-lived species have a fast pace of ageing, and long-lived species have a slow pace of ageing. Pace describes how quickly the clock of life ticks away. For humans it ticks slowly, for small songbirds like the robin it ticks very fast. At the age of 15, only 2 out of 100,000 girls in Sweden die, but one out of every two women aged 110 will die. This large difference in mortality at the beginning and end of adult life means that for humans the shape of ageing is steep, whereas in other species like the common swift it is shallow. And in some species the risk of death can even fall with age, with older individuals having the least risk of dying. This seems to be the case for the desert tortoise, and for alligators or crocodiles. ... Comparing robins with Swedish women, humans have a slow pace of ageing whereas the robin's is fast, so in terms of length of life the humans are doing best. But if we look at the impact ageing has on death rate the robin wins. Its shape of ageing is fairly flat whereas the humans' is steep, indicating that death rates increase markedly with age ... Not all species with short lives live fast and die young. Robins do, but mountain sheep do things differently. They also live pretty fast but die older. From the data I have, it seems that live fast die young is only one option; you can also live fast and die older, or live slower and die young, or live slow and die old. There might be every combination in nature. That's something we need to find out in the future with better data."

Link: http://www.science20.com/news_articles/live_fast_still_die_old-76345

Around these parts Aubrey de Grey and the SENS Foundation should require no introduction. His advocacy and the Foundation's work on the science of repairing aging is well known, and has been mentioned here at Fight Aging! too many times to count. In my eyes, the Strategies for Engineered Negligible Senescence (SENS) continue to be the best extant plan for extending human life span as rapidly as possible - and within our lifetimes. The more funding that is devoted to realizing that plan, the better all of our futures will be.

I noticed that a podcast interview with de Grey is up at the Singularity Weblog:

Last time I had Dr. Aubrey de Grey on Singularity 1 on 1 the interview turned out to be a hit. In fact it is still by far the most popular podcast that I have done and the audio file has been listened to or downloaded over 30,000 times. Given Aubrey's popular appeal and the importance of his work, it is no surprise that I am very happy to have him back for a second interview. ... During this conversation I ask Dr. de Grey to discuss issues such as: the term natural death and its impact; the publicity and importance of two long-awaited documentaries about Ray Kurzweil - Transcendent Man and The Singularity is Near; traditional metabolic and more recent DNA tests such as the ones done by 23andMe and others; the slow developmental process of new drugs and therapies, and the problems of taking them from testing in lab rats to humans; the Thomas Malthus argument of overpopulation and Aubrey's reply to it.

Head on over there to watch or listen.

The investigation of the mechanisms of calorie restriction continues apace. Here, researchers "report for the first time that deactivation of a protein called CRTC1 in roundworms increases their lifespan, most likely mediating the effects of calorie restriction. Previously, researchers knew hunger promoted longevity by activating an enzyme called AMPK, which senses that food is scarce and pushes cells into a low energy state. ... We knew AMPK was a major energy sensor but didn't know what it was talking to. Our goal was to understand the genetic circuitry that registered that response. ... It was clear that one pathway that coordinated metabolism with growth in response to nutrients was AMPK signaling. Studies had also suggested that AMPK might regulate lifespan in worms. What was not known was what factors downstream of AMPK mediated those effects. ... they searched the genome of Caenorhabditis elegans for likely AMPK targets, and identified one suspect encoding a protein called CRTC1, which was expressed at the same time and place as AMPK. To determine if CRTC1 played any role in lifespan, the team fed worms an inhibitory RNA engineered to deplete them of CRTC1 protein. When they measured the worms' lifespan-normally about 3 weeks-they found that worms fed the anti-CRTC1 RNA lived a whopping 40% longer, suggesting that AMPK retards aging by antagonizing CRTC1 activity. ... AMPK deactivated CRTC1 by adding phosphates to a specific region of the CRTC1 protein, an effect equivalent to eliminating CRTC1 altogether. Likewise, when the worms were fed an inhibitory RNA depleting them of an enzyme that lops off the CRTC1 phosphates, they lived longer, showing that AMPK and the lopper - known to scientists as calcineurin - determine lifespan by controlling the extent to which CRTC1 is phosphorylated."

Link: http://www.newswise.com/articles/hungering-for-longevity-salk-scientists-identify-the-confluence-of-aging-signals

From ScienceDaily: "It has been long known that stress plays a part not just in the graying of hair but in hair loss as well. ... Now, a team [that] was investigating how stress affects gastrointestinal function may have found a chemical compound that induces hair growth by blocking a stress-related hormone associated with hair loss - entirely by accident. ... Our findings show that a short-duration treatment with this compound causes an astounding long-term hair regrowth in chronically stressed mutant mice. This could open new venues to treat hair loss in humans through the modulation of the stress hormone receptors, particularly hair loss related to chronic stress and aging. ... the researchers had been using mice that were genetically altered to overproduce a stress hormone called corticotrophin-releasing factor, or CRF. As these mice age, they lose hair and eventually become bald on their backs, making them visually distinct from their unaltered counterparts. The [researchers] had developed the chemical compound, a peptide called astressin-B, and described its ability to block the action of CRF. ... researchers injected the astressin-B into the bald mice to observe how its CRF-blocking ability affected gastrointestinal tract function. .... About three months later, the investigators returned to these mice to conduct further gastrointestinal studies and found they couldn't distinguish them from their unaltered brethren. They had regrown hair on their previously bald backs."

Link: http://www.sciencedaily.com/releases/2011/02/110216185406.htm

The latest issue of Rejuvenation Research is available online, and it opens with what is perhaps one of the best of points to make in a world in which people are dying all around us:

I welcome Dr. Paula Moreira as a new member of our editorial board, but for the worst possible reason. Moreira has been appointed as a replacement for Mark Smith, a fellow professor at Case Western Reserve University, who tragically died in a car accident late last year. What is even worse is that Smith is not the only loss that the field of biogerontology has suffered in 2010. In fact, I am aware of fully five other researchers who died during 2010. Amir Abramovich (whose Ph.D. advisor has penned a brief obituary that appears later in this issue) and Estela Medrano also succumbed to road accidents. James Joseph died from complications following heart surgery. Chris Heward was the victim of a particularly aggressive esophageal cancer. And Bob Butler died very suddenly of leukemia.

...

I have chosen to highlight these sombre events in this space not only to commemorate lost friends and colleagues. My main reason for doing so is to draw attention to the questionable validity of our tendency to grieve especially intensely for those who die when still highly active. Though I share this tendency, I think it deserves scrutiny, because it is founded on an assumption that profoundly contradicts the motivation for the work to which we, as did the colleagues I have just listed, dedicate our lives.

Aging kills people, just as cars do. There are only two things that distinguish aging from other killers: it kills people very slowly, only after gradually and progressively debilitating them over many years, and it only kills people who were born quite a long time ago. The combination of these features seems to be the only available explanation for why we so meekly and calmly accept the deaths of so vast a number of people from aging, while feeling much more intense anger and despair at the comparatively rare deaths that occur in the industrialized world at younger ages.

...

Is it somehow OK, or at least only a little bit sad, when someone dies of "natural causes" after "a good innings"? I would suggest that it is not OK.

Ageism permeates our societies, and our descendants will look back in disgust and horror at the way in which we allowed our historical legacy of prejudice to suppress and slow down progress towards the biotechnologies of rejuvenation. We younger folk write off the old in so many ways, and in doing so each of us is only sticking the knife into the person we'll be a few decades down the line - and teaching our children to do exactly the same. Every death is a tragedy, but so many people work so hard to pretend otherwise.

Old people suffer from a terrible debilitating medical condition: aging. Why view them any differently than the victims of any other deadly disease? If not weighed down by the degenerations of aging and the knowledge of suffering a certainly terminal condition, elderly folk could contribute greatly to all fields of human endeavor, applying the experience and knowledge of a lifetime - or adeptly applying the savings of a lifetime to fund the work of others. We would all be far wealthier if the ongoing ability to create value offered by human beings was not destroyed after a bare few decades of productivity.

Even if it wasn't the case that it is in our immediate economic self-interest to build rejuvenation biotechnologies, working to cure aging would still be the greatest of charitable causes. No other aspect of human biology or the human condition causes as much pain and death.

Aging is a horror, and it twists our society into further horrors - such as the often shameful ways in which the young treat the old. The sooner that aging can be repaired and removed as a threat to human existence, the better the human condition will become.

From the Monterey Herald: " Within a Northeast Ohio lab, a hairless mouse is growing an ear from the cells of a Wadsworth, Ohio, preschooler. Dr. William Landis, the G. Stafford Whitby Chair of Polymer Science at the University of Akron, is leading groundbreaking, tissue-engineering research to grow human cartilage - first in the lab, now in animals and, eventually, in patients. His work is part of a fast-developing field that could help millions of patients repair injuries, replace worn body parts or fix birth defects with tissue grown from their own cells in the not-so-distant future. ... Kyle Figuray's parents agreed to be the first area participants and donors of his otherwise useless cartilage. The healthy, friendly 5-year-old was born with a congenital defect that caused the exterior ear and ear canal on his right side to develop improperly. Typically, the malformed ear cartilage is discarded as medical waste after it's removed during the first of three procedures to craft a new ear out of rib. Instead, the tissue removed [was] placed inside a vial and shared with Landis' research team, who carefully cleansed the cells and fed them special nutrients to coax them to proliferate in the lab. A few weeks later, enough cells were available for researchers to 'seed' them onto a biodegradable, biocompatible polymer scaffold. A few days later, the seeded ear scaffold was implanted under the skin of a hairless mouse ... The mouse will be studied over the next year to determine how the cells are behaving and progressing toward normal cartilage. If all goes well, the biodegradable polymer scaffold should disappear, leaving behind only Kyle's cartilage cells in the shape of an ear. The hope is that an affected person's cells someday can be harvested, seeded onto similar polymer scaffolds and implanted under the patient's own skin in the abdomen or back until they grow into replacement tissue. At that point, the new tissue could be removed and used to replace the patient's injured or defective tissue."

Link: http://www.montereyherald.com/science/ci_17411698

Research into Laron dwarfism in a population in Ecuador has been taking place for a few years now: "People living in remote villages in Ecuador have a mutation that some biologists say may throw light on human longevity and ways to increase it. The villagers are very small, generally less than three and a half feet tall, and have a rare condition known as Laron syndrome or Laron-type dwarfism. ... though cancer was frequent among people who did not have the Laron mutation, those who did have it almost never got cancer. And they never developed diabetes, even though many were obese, which often brings on the condition. ... [this is] an opportunity to explore in people the genetic mutations that researchers [found] could make laboratory animals live much longer than usual. ... The Laron patients' mutation means that their growth hormone receptor lacks the last eight units of its exterior region, so it cannot react to growth hormone. In normal children, growth hormone makes the cells of the liver churn out another hormone, called insulinlike growth factor, or IGF-1, and this hormone makes the children grow. If the Laron patients are given doses of IGF-1 before puberty, they can grow to fairly normal height. This is where the physiology of the Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal."

Link: http://www.nytimes.com/2011/02/17/science/17longevity.html

There is clearly a point in Alzheimer's, and other neurodegenerative diseases, beyond which the damage caused by the condition is irreversible. Neurons die, and in large enough numbers to destroy vast swathes of information held in the brain - the very foundation of who you are, and the vital components of systems needed to live a normal life. All is not gloom, however. Studies in past years have suggested that up to that point, much of the loss of function that accompanies Alzheimers is in principle reversible:

Some evidence suggests that the worst effects of Alzheimer's disease can be repaired - that memories are not destroyed, but rather become inaccessible.

Another recent study adds to this picture:

Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off.

Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease - in part, at least.

For yet another consideration of early to mid-stage Alzheimer's as a form of dynamic blockage of memory access, you might also look at the effects of some newer anti-inflammatory treatments:

The [study from 2008] documents a dramatic and unprecedented therapeutic effect in an Alzheimer's patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine.

Putting aside a discussion of the mechanisms by which this happens, the very fact that it can happen demonstrates the possibility of reversing the worst aspects of Alzheimer's. Thus memories and the working structures of the brain must remain largely intact until fairly late in the progression of the disease.

A promising open access study: "Transplanting autologous renal progenitor cells (RPCs), (kidney stem cells derived from self-donors), into rat models with kidney damage from pyelonephritis - a type of urinary infection that has reached the kidney - has been found to improve kidney structure and function. ... Advancements in stem cell therapies and tissue engineering hold great promise for regenerative nephrology. Our RPC transplant study demonstrated benefits for pyelonephritis, a disease characterized by severe inflammation, renal function impairment and eventual scarring, and which remains a major cause of end-stage-renal disease worldwide. ... The researchers divided 27 rats into three groups, two of which were modeled with an induced pyelonephritis in their right kidneys, while the third group did not have induced disease. RPCs were obtained from the diseased animals' left kidneys and injected into the right kidney six weeks later. Two weeks after injection, tubular atrophy was reduced. After four weeks, fibrosis was reduced and after sixty days, right renal tissue integrity was 'significantly improved.' ... We propose that kidney augmentation was mainly due to functional tissue regeneration following cellular transplantation. Kidney-specific stem/progenitor cells might be the most appropriate candidates for transplantation because of their inherent organ-specific differentiation and their capacity to modulate tissue remodeling in chronic nephropathies. ... The researchers concluded that because renal fibrosis is a common and ultimate pathway leading to end-stage renal disease, amelioration of fibrosis might be of major clinical relevance."

Link: http://www.eurekalert.org/pub_releases/2011-02/ctco-sct021411.php

From the Telegraph: "India's first set of government-approved clinical trials of stem cells on patients with chronic obstructive lung disease, diabetes, liver cirrhosis and osteoarthritis are likely to begin in five cities in April this year. A Bangalore-based company, Stempeutics Research, has received approval from the country's drug regulatory agency to evaluate the efficacy of its stem cells on these four incurable diseases after safety assessments over the past year on patients with cardiovascular disease. The efficacy - Phase II - trials are likely to begin on small groups of volunteer patients offered the experimental treatment in collaborating hospitals in Bangalore, Kochi, Delhi, Mangalore and Manipal, a senior Stempeutics official said. Each volunteer patient will receive a dose of mesenchymal stem cells derived from the bone marrow of healthy persons. The stem cells, coaxed to proliferate in a broth of laboratory biochemicals, will be injected at the site of illness - the pancreas, the liver, the lungs, or the bone - where they are expected to stimulate resident stem cells and regenerate the damaged or lost tissue. While private and even government hospitals have in the past offered stem cell therapy to patients with intractable conditions, the proposal by Stempeutics is the first with formal approval from regulators for chronic obstructive pulmonary disease (COPD), diabetes, liver cirrhosis and osteoarthritis."

Link: http://www.telegraphindia.com/1110216/jsp/frontpage/story_13589821.jsp

The Science for Life Extension Foundation is a Russian organization consisting of advocates and aging researchers. They are similar to the SENS Foundation in that they undertake a mix of fundraising, directing research, organizing events, advocacy for longevity science, and publishing on potential methodologies to extend the healthy human life span. These two groups even share some members and advisors in common - it's a small world these days, after all, and aging research is not a large community to begin with. That is one of many things we like to see change over the next decade or two: if you want rapid progress, there need to be many researchers at work.

The Science for Life Extension Foundation has published a number of professional quality documents that can be downloaded in PDF format from their website. Unfortunately not all of them are available in English, and automated translation of PDFs remains somewhat hit and miss. I did want to direct your attention to one of the documents, however, which is entitled "25 Scientific Ideas of Life Extension." It is a very elegantly designed, very clear booklet aimed at investors. The PDF packages up a series of scientific research programs aimed at extending human life into compelling elevator pitches - but just saying that doesn't do it justice. It really is very well done indeed, and you should take a look:

I picked out one of the twenty-five that focuses on a research theme you might be familiar with, as I've mentioned it in the past. If you look back in the Fight Aging! archives, you can read more about Cuervo's work on autophagy and lysosomal receptors:

• A Little More On Preventing Decline in Liver Function With Age
• An Update on Cuervo's Autophagy Research

In experiments, livers in genetically modified mice 22 to 26 months old, the equivalent of octogenarians in human years, cleaned blood as efficiently as those in animals a quarter their age. By contrast, the livers of normal mice in a control group began to fail. ... While her paper does not show increased survival rates among the mice, le Couteur, who has advised her recently on the research, says Cuervo does have data on improved survival rates which she intends to publish.

The selective destruction of immune cells in the old should greatly improve their failing immune function. Much of that decline results from an imbalance of cell types, while other issues such as autoimmune diseases may be the result of a small population of misconfigured cells: "Aberrant production of autoantibodies by inappropriately self-reactive plasma cells is an inherent characteristic of autoimmune diseases. Several therapeutic strategies aim to deplete the plasma cell pool, or to prevent maturation of B cells into plasma cells. However, accepted views of B-cell biology are changing; recent findings show that long-lived plasma cells [contribute] to the maintenance of humoral memory and, in autoimmunity, to autoreactive memory. As a consequence of their longevity and persistence, long-lived plasma cells can support chronic inflammatory processes in autoimmune diseases by continuously secreting pathogenic antibodies, and they can contribute to flares of symptoms. As long-lived plasma cells are not sufficiently eliminated by current therapies, these findings are extremely relevant to the development of novel concepts for the treatment of autoimmune diseases. Thus, long-lived plasma cells appear to be a promising new therapeutic target." It would be a good day for a great many patients if it turns out that autoimmune diseases can be eliminated or greatly reduced in severity by destroying just a small population of cells. We already know that complete destruction and recreation of the immune system works, so this seems like a reasonable direction to explore.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21283146

Some thoughts on wrong directions in medicine from Chronosphere: "The first thing that anyone needs to understand about medicine is what its proper goal is. That's actually pretty simple: to cure disease and maintain good health. No further qualifications are necessary. Once that proposition is accepted, it then should become obvious that the end goal, and the ultimate ideal of medicine, is to keep people alive and in good health indefinitely. ... So, despite the fact that most people, when asked, will recoil in horror from the notion of personal, biological immortality, the fact is that that is exactly what they expect, exactly what they want, and exactly what they will effectively demand. Unfortunately, most of the medicine we practice today is not only not going to provide immortality any time soon ... Halfway technology represents the kinds of things that must be done after the fact, in efforts to compensate for the incapacitating effects of certain diseases whose course one is unable to do very much about. By its nature, it is at the same time highly sophisticated and profoundly primitive ... It is characteristic of this kind of technology that it costs an enormous amount of money and requires a continuing expansion of hospital facilities ... It is when physicians are bogged down by their incomplete technologies, by the innumerable things they are obliged to do in medicine, when they lack a clear understanding of disease mechanisms, that the deficiencies of the health-care system are most conspicuous ... The only thing that can move medicine away from this level of technology is new information, and the only imaginable source of this information is research. The real high technology of medicine comes as the result of a genuine understanding of disease mechanisms and when it becomes available, it is relatively inexpensive, relatively simple, and relatively easy to deliver."

Link: http://chronopause.com/index.php/2011/02/14/achieving-truly-universal-health-care/

The silliest of all arguments raised against engineered human longevity have always been those involving forms of stasis - the unlikely specters of boredom and stagnation, for example. But to be alive is to be a force for change. No-one is static, not even those folk who try to be or who think they are.

It recently occurred to me that one could build a fairly strong counterpoint to the "immortal dictator" form of stasis argument by pointing to the politics of past centuries in times when life expectancies were much shorter. The spans of governments and leaders back then were not all that different to what we see today - but today the life expectancies of people at every age are notably longer. So why don't we suffer empires to put the span of Rome to shame, and nations in which the commonplace span of social and political power is far longer than just a few years?

The answer of course being that life is change. Carpe diem!

So it was in the spirit of change and improvement that I turned off the Longevity Meme website this past weekend: switched the DNS to point to Fight Aging!, cancelled the hosting service, and then sent out the first weekly newsletter to go out under the Fight Aging! banner rather than that of the Longevity Meme. This has been in the works for a while, but here we are now with the deed done.

The Longevity Meme had a ten year run as a project, first assembled in a crude format back in 2001 - when I'd had enough of just thinking about longevity science and wanted to actually do something about it. As a non-biologist, writing and advocacy seemed like a sensible path forward. Evidently I'm not cut from the same fabric as folk like Aubrey de Grey and Kevin Perrott, once non-biologists, whose response to the same urge was to take a hard right turn in life and become biologists working in the field of aging research. The scale of the challenge is such that we need as many such motived people as we can get.

Ten years of managing the Longevity Meme spanned my observer's education in the biology of aging and longevity science, as well as the rise of the present younger generation of advocacy groups such as the Methuselah Foundation, SENS Foundation, Immortality Institute, and many others. I can't claim anything in this beyond it being the zeitgeist of the last decade: it was in the air. In ten years we've moved from a fringe environment - in which the main course of action was persuading people to take seriously the prospects for longevity science - to a more mainstream environment in which raising support and large sums of money for work on rejuvenation biotechnology is the primary, plausible goal. The Longevity Meme was more a project for the old environment, and Fight Aging! is more a project for the new.

I am beginning to think the the waters of education and public awareness have risen far enough for the act of raising money for longevity research to be a work of advocacy in and of itself. The process of raising funds - of networking, education, and persuasion - conveys a message in and of itself: that this ideal of defeating aging is real and here and moving. It isn't an abstract future, a vague something, but rather tangible progress that is taking place in laboratories right here and now.

Life is change.

So I will be thinking more on the topic of how to steer money towards the best research facilities and goals in the years ahead. For now, Fight Aging! is as you see it: a source of news and opinions on the topic of engineered human longevity. One of those opinions is, as always, that you should head on over to either the Methuselah Foundation or the SENS Foundation and make a donation to support their work. Or persuade a friend to do the same: that is where the future starts, by voting with your wallet.

Via EurekAlert!: "Scientists [have] produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder. Although the findings were in animal models of the disease, the effectiveness of the compound, combined with its potential to be taken orally, offers the tantalizing possibility of a potentially useful future therapy for Parkinson's disease patients. ... The new small molecule - labeled SR-3306 - is aimed at inhibiting a class of enzymes called c-jun-N-terminal kinases (JNK). Pronounced 'junk,' these enzymes have been shown to play an important role in neuron (nerve cell) survival. As such, they have become a highly viable target for drugs to treat neurodegenerative disorders such as Parkinson's disease. ... The SR-3306 compound, which has been in development [for] several years, performed well in both cell culture and animal models. In cell culture, the compound showed greater than 90 percent protection against induced cell death of primary dopaminergic neurons, while in mouse models of induced neuron death, the compound showed protective levels of approximately 72 percent. The scientists went one step further, testing the new compound in a rat model, which duplicates the physical symptoms often seen with the human disease - a pronounced and progressive loss of motor skills. The results showed SR-3306 provided a protection level of approximately 30 percent in the brain, a level that reduced the dysfunctional motor responses by nearly 90 percent."

Link: http://www.eurekalert.org/pub_releases/2011-02/sri-src021111.php

Lithium is known to extend life in nematode worms, though I haven't seen much further exploration of the mechanism. Here, Japanese researchers show that lithium intake is also associated with human mortality - though as for all such large statistical studies, one would want to see confirming work from other parts of the world before taking it as fact: "Lithium is a nutritionally essential trace element predominantly contained in vegetables, plant-derived foods, and drinking water. Environmental lithium exposure and concurrent nutritional intake vary considerably in different regions. We here have analyzed the possibility that low-dose lithium exposure may affect mortality in both metazoans and mammals. ... Based on a large Japanese observational cohort, we have used weighted regression analysis to identify putative effects of tap water-derived lithium uptake on overall mortality. Independently, we have exposed Caenorhabditis elegans, a small roundworm commonly used for anti-aging studies, to comparable concentrations of lithium, and have quantified mortality during this intervention. ... In humans, we find here an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals ... Consistently, we find that exposure to a comparably low concentration of lithium chloride extends life span of C. elegans ... Taken together, these findings indicate that long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21301855

There's always something interesting in the news when it comes to progress in regenerative medicine and tissue engineering. This is the sort of research community we want to see for every field that might impact human aging and longevity: large, thriving, dynamic, and attracting plenty of attention and funding. The practical result is that we live in exciting times - organ regrowth is right around the corner, as is the prospect of meaningful repair or replacement of many types of aged tissue. Regenerative medicine is not a one-stop solution for all of aging, but it is one of the necessary pillars of the true rejuvenation biotechnology that will be developed in the decades to come.

Here are a few articles that caught my eye of late; the mainstream media seems to be picking up the level of attention they are giving to the cutting edge of regenerative medicine these days.

Seeing local scientists at heart of regenerative medicine

In one lab, a surgeon builds a pink, pulsing heart, cell by cell. In another, a researcher literally sprays new skin onto severely burned patients. Elsewhere, a scientist re-creates the delicate folds of the ear - on the back of a mouse. Sound like science fiction? It already is science: Researchers in Boston and beyond are building everything from blood vessels to internal organs, using engineering tricks and dome-like bioreactors. Tonight, in 'How to Build a Beating Heart,' National Geographic Explorer investigates those efforts to transform human health, revealing the pulse-quickeningly cool side of regenerative medicine.

Building body parts: Saving lives, salamander style

If an injured salamander can grow a new limb, why can't a human? Maybe they can, say researchers at the Armed Forces Institute of Regenerative Medicine. Starting with stem cells from patient's bodies, scientists at this Wake Forest University facility have grown 22 different types of tissues and organs. Lives are being saved and more amazing successes are on the way.

Skin cells help to develop possible heart defect treatment in first-of-its-kind Stanford study

Using skin cells from young patients who have a severe genetic heart defect, Stanford University School of Medicine scientists have generated beating heart cells that carry the same genetic mutation. The newly created human heart cells - cardiomyocytes - allowed the researchers for the first time to examine and characterize the disorder at the cellular level. ... the investigators also report their identification of a promising drug to reverse the heart malfunction - for which there are currently no decent treatments - after using these newly created heart cells to check the effects of a plethora of compounds.

College of Veterinary Medicine to perform an animal stem cell first

The first animal stem cell procedure in Oregon done entirely in a veterinary facility is scheduled for Thursday at the Oregon State University College of Veterinary Medicine. The procedure will be performed on Basco (pronounced "Bosco"), a 7-year-old German Shepherd suffering from osteoarthritis in his left rear hip. ... Fat tissue is removed from the animal, the stem cells are separated and activated, and then injected into the affected area. Within three to four weeks of the procedure, Basco should be moving well, with little or no pain, Medi-Vet predicted.

Veterinary medicine is far ahead in its application of first generation stem cell therapies; if you're a human in need of the same sort of treatment, you'll have to leave the US to find it. The principle effect of heavy US regulations on medical development is to ensure that working, beneficial, reasonably safe treatments take a very long time to come to the clinic and are very expensive when they arrive. Fortunately the FDA can't do anything about the competitive service providers and medical research and development groups in other parts of the world. Thus, absent a sea change in the state of regulation in the US, medical tourism will be a part of all our futures, and we will benefit greatly from the fact that at least some parts of the world are not as shackled and held back by a full-on command economy medical system.

I'm always pleased to see more good writing on the topic of longevity science: "To extend our longevity, we'll have to advance in stages. ... With a healthy lifestyle and some luck (absence of accidents and natural disasters) we not only can increase our lifespan, we can increase the health in that lifespan and postpone debilitating illness to the very end of our life ... To go beyond this achievable life extension, we need more advances in the basic sciences. Considering aging as a disease is new concept. It will take time before we accept this not just as wishful thinking but as a real possibility in our lifetime. The end of aging does not mean that we will never die; we will still die of other diseases, accidents, or natural disasters but no longer of aging itself. ... Aging is not yet recognized as a disease. Some among us would like the Food and Drug Administration (FDA) to recognize it as a disease so that we could get funding for basic, translational, and clinical research on aging. ... These changes will be implemented incrementally. The unprecedented biological and technological evolution we face today will be the driving force for social, economic, and even political changes. Working conditions will change significantly: retirement will be changed, people will no longer retire after a certain age, they will take time off from work every few years and then return to it afterwards. Our goal is not to reach immortality but to postpone and eventually prevent aging. For now and the immediate future we can change our lifestyle toward healthier living. This will buy us time so that we can survive long enough for the advances in basic sciences, which will be made in the next 15 to 20 years, helping us move to the next stage where aging will no longer be the biggest killer of our species."

Link: http://www.brooklyneagle.com/categories/category.php?id=41234

There is no shortage of people trying to convince us that degenerating into frailty, suffering, and death is a wonderful thing: "Mr Agronin is an optimist. He does not deny - how could he? - the sufferings and indignities of old age. Scanning slices of old brain, 'stained and prepped for the microscope', his eye is unsparing: 'the aged folds' like 'the withered meat of a walnut', the blood vessels like 'hardened tendrils', the 'small plaques of toxic amyloid protein surrounded by a debris field of dead neurons'. But alongside the science, he sees something else: the people themselves. Old age, he says, has become our blind spot, neglected by the medical profession, lumped together with dementia and disease, something to be endured, dreaded, mercifully pre-empted, or even - as one researcher in the field, Aubrey de Grey, argues - reversed. Mr Agronin, by contrast, embraces it. He sees it as intrinsic to life, with its own 'ways and meanings', its particular wisdom. Even at its most tenuous and hollowed out, he finds some shape, a sense of cyclic pattern. In an almost mystical passage, inspired by his professor, Erik Erikson, a psychologist, Mr Agronin likens life to a stream which eventually seeps down unseen into the bedrock, and opens 'like a flower into the aquifer below'." From where I stand, there needs to be more of a healthy dread of aging - perhaps that would motivate more people to help develop the rejuvenation biotechnologies that can do something about it. To try to pretend that aging to death, suffering terribly along the way, is just peachy keen has an air of desperate madness to it.

Link: http://www.economist.com/node/18111554

This research has been doing the rounds:

This week researchers from the Dana-Farber Cancer Institute reported that the length of telomeres - which shorten with age - determines virtually every aspect of aging from wrinkles and gray hair to the onset of dementia, diabetes, and heart disease. At least that was the case in the mice they studied in a report published in Nature.

"We think we've identified the core pathway that really helps explain many different theories of aging," says study co-author Dr. Ronald DePinho, a geneticist at Dana-Farber. "Our study provides a unified field theory for aging."

In a nutshell, once telomeres shorten to a particular length, aging accelerates. Shortened telomeres allow the cell's DNA to become damaged, which activates a gene, p53. This sets off a warning to shut down the cells' normal growth and division cycle until the damage can be fixed or, if not, the cells die. At the same time, cells with short telomeres have power plants, or mitochondria, that are no longer operating at full capacity. This leads to malfunction in crucial organs like the brain, heart, liver, and pancreas, as well as a loss of muscle, and eventually extreme weakness and frailty.

(The paper is at Nature if you're the sort who likes to read primary sources). That's an ambitious declaration from the researcher quoted above - I can only imagine it's taken somewhat out of context and then hyped up by the science writer for the introductory paragraph, as it is certainly the case that damaged mitochondria and shortening telomeres are only two of the possible reasons we suffer age-related degeneration. Many of the other causes of aging involve a build up of varying forms of damaging waste product that the body cannot remove - mechanisms which are quite capable of causing disability and death on their own, telomere shortening or no telomere shortening.

That said, telomeres, mitochondria, and p53 are all large and healthy areas of research when it comes to the biology of aging. I imagine that anyone would be pleased to produce good evidence that might mechanically tie them all together, such that one or more are secondary effects rather than primary causes. From an economic perspective, we should all be hoping that some of our present candidates for the primary causes of aging turn out to be secondary effects - because then we don't have to devote any time towards developing repair biotechnologies to fix them.

On a closer reading of the new research, I have to say that it looks to me very much like an independent confirmation of discoveries from 2007 and 2008 relating to mitochondrial damage, telomere length, and the enzyme telomerase. In a nutshell, it may be that telomere shortening is entirely driven by mitochondrial dysfunction:

Researchers have put forward evidence to suggest that telomere shortening is caused by accumulated damage to mitochondrial DNA - essentially collapsing two areas of intense interest for gerontologists down to one root cause, if confirmed. ... [It may be the case that] poorly functioning mitochondria lead to telomere shortening, and telomerase somehow improves mitochondrial function to prevent that shortening. This is in place of the more expected path of undoing ongoing telomere shortening by adding extra repeat sequences to the end of the telomeres - that being the better understood function of telomerase.

I don't immediately see anything in the Nature paper that would rule out this interpretation of the link between these two fundamental mechanisms of aging. Like the earlier researchers, this present group also found that boosting telomerase activity improved mitochondrial function, though I believe they are arguing that the improved function happens as a secondary result of interactions between telomere length and p53. There's certainly plenty of room amidst the uncertainty for contradictory interpretations at this stage.

Time here looks at Ray Kurzweil's timeline for the development of biotechnologies that can defeat aging: repair the old, remove biological damage, and eliminate frailty and age-related death. "The Singularity isn't just an idea. it attracts people, and those people feel a bond with one another. Together they form a movement, a subculture; Kurzweil calls it a community. Once you decide to take the Singularity seriously, you will find that you have become part of a small but intense and globally distributed hive of like-minded thinkers known as Singularitarians. ... At the 2010 summit, which took place in August in San Francisco, there were not just computer scientists but also psychologists, neuroscientists, nanotechnologists, molecular biologists, a specialist in wearable computers, a professor of emergency medicine, an expert on cognition in gray parrots and the professional magician and debunker James 'the Amazing' Randi. ... After artificial intelligence, the most talked-about topic at the 2010 summit was life extension. Biological boundaries that most people think of as permanent and inevitable Singularitarians see as merely intractable but solvable problems. Death is one of them. Old age is an illness like any other, and what do you do with illnesses? You cure them. Like a lot of Singularitarian ideas, it sounds funny at first, but the closer you get to it, the less funny it seems. It's not just wishful thinking; there's actual science going on here. ... People have begun to realize that the view of aging being something immutable - rather like the heat death of the universe - is simply ridiculous. It's just childish. The human body is a machine that has a bunch of functions, and it accumulates various types of damage as a side effect of the normal function of the machine. Therefore in principal that damage can be repaired periodically. This is why we have vintage cars. It's really just a matter of paying attention. The whole of medicine consists of messing about with what looks pretty inevitable until you figure out how to make it not inevitable." I don't see it as plausible that we'll have everything in hand by 2045, but if we make a good start now, then we could have enough to put us into actuarial escape velocity - gaining life expectancy faster than we age, and thus able to wait for far better technologies that arrive later.

Link: http://www.time.com/time/printout/0,8816,2048138,00.html

The early posts at Chronosphere are well done and worth reading. The theme is a detailed and picture-strewn look at the history of cryonics, mixed in with considerations of our presently imperfect society and where it might be going next: "Chronosphere is your gateway to a fundamentally new way of living - in pursuit of physical immortality in a world of our own making - free from the tyranny of time, and the burden of injustice. Chronosphere will explore and create interfaces with the scientific, technological, social and moral resources needed to achieve these ends. Because we are all at risk of dying, cryonics will be a central focus of Chronosphere for the foreseeable future, but will be by no means be the only technology explored here. Interventive gerontology, with a strong emphasis on immediate, or very near term interventions to slow cognitive aging, will also be explored in detail. Join us on our quest to transcend the limits of time!"

Link: http://chronopause.com/

By virtue of the fact that very large sums of venture capital, big pharma investment, and public funding have been sunk into the examination of sirtuins in connection with longevity in mammals, I think we'll see a strong sirtuin research contingent in the scientific community for some years to come - and this regardless of the ultimate merits of this work. While there are promising signs that sirtuins may do something useful in terms of enhancing cellular housekeeping, after some years of research we have yet to see any of the promise of slowed aging that looked possible at the outset. See, for example:

• A Possible Reason For Sirtuin Uncertainty
• Critiquing the Sirtuin Model of Calorie Restriction

Research and development always takes longer than expected, but at this point I look at research into sirtuins as an early step forward on a much longer road - a part of the foundations of some later work, and producing little of direct use in and of itself. The newer technologies and newer companies who work on the same strategy of slowing aging via identification of ways to manipulate metabolism will leap over the work of the last five years, producing a hundred-fold more genetic and biochemical data in the process. Biotechnology is advancing so rapidly that each generation of development is made obsolete before it even hits its stride. It will be interesting indeed to see what comes after the present generation of biotech startups like Genescient and Halcyon Molecular.

But back to sirtuins: here is an optimistic open access paper from researchers who do see a bright future for the development of sirtuin-based therapies.

How does aging occur? Can we delay the aging process? These are questions that have been asked for hundreds if not thousands of years.

...

Aging is one of the most fundamental biological processes. It results in a decline in physiological function and an increased risk for pernicious diseases such as cancer. Oxidative stress has been proposed as a major cause of aging, but experimental tests of this hypothesis have been discouraging. Calorie restriction (CR) prevents age-related decline, but there are still gaps in our knowledge of the exact mechanisms underlying this feat. Finally, a tenuous balance exists between aging and cancer, calling for a search for interventions that prevent both aging and cancer. Recent work on the mammalian sirtuin SIRT3 has shed light on these long-standing issues and suggested new approaches to ameliorate the ravages of aging.

You might look back into the Fight Aging! archives for a quick overview of the relevance of SIRT3 to oxidative stress and longevity:

This research group proposes that Sirt3 acts on longevity through increasing antioxidants - we should all be appropriately skeptical, given the very mixed evidence for links between cellular antioxidants and longevity. That said, Sirt3 is located in the mitochondria, and the demonstrations of extended life spans through increased antioxidants have involved targeting those antioxidants to the mitochondria.

When considered in the broader context, a great many lines of research turn to point towards our mitochondria and the damage they suffer over time. All the more reason to direct greater efforts towards nascent mitochondrial repair technologies rather than yet more metabolic tinkering.

You might recall that the olm (Proteus anguinus) is a type of small salamander that lives as long as we do. Here researchers point out that olm life span is inconvenient for some theories of aging: "Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories." Yet there are still the studies demonstrating extended life span through targeting antioxidants to mitochondria, which imply that at least so far as those cellular structures are concerned, oxidative damage is very important. It may be that the olm, like naked mole rats, has mitochondria that are highly resistant to damage in comparison to other species.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21290398

A fair chunk of degenerative aging is caused by the accumulation of various kinds of damaging biochemicals, and here dry macular degeneration is added to that list: "A team of researchers, led by University of Kentucky ophthalmologist Dr. Jayakrishna Ambati, has discovered a molecular mechanism implicated in geographic atrophy, the major cause of untreatable blindness in the industrialized world. ... Concurrent with this discovery, Ambati's laboratory developed two promising therapies for the prevention of the condition. ... Geographic atrophy, a condition causing the death of cells in the retina, occurs in the later stages of the 'dry type' of macular degeneration, a disease affecting some 10 million older Americans and causing blindness in over 1 million. There is currently no effective treatment for geographic atrophy, as its cause is unknown. Ambati's team discovered that an accumulation of a toxic type of RNA, called Alu RNA, causes retinal cells to die in patients with geographic atrophy. In a healthy eye, a 'Dicer' enzyme degrades the Alu RNA particles. ... We discovered that in patients with geographic atrophy, there is a dramatic reduction of the Dicer enzyme in the retina. When the levels of Dicer decline, the control system is short-circuited and too much Alu RNA accumulates. This leads to death of the retina. ... Alu elements make up a surprisingly large portion - about 11 percent by weight - of the human genome, comprising more than 1 million sequences. However, their function has been unknown, so they have been called 'junk' DNA or part of the 'dark' genome. The discovery of Alu's toxicity and its control by Dicer should prove of great interest to other researchers in the biological sciences ... Ambati's team developed two potential therapies aimed at preventing geographic atrophy and demonstrated the efficacy of both approaches using laboratory models. The first involves increasing Dicer levels in the retina by 'over-expressing' the enzyme. The second involves blocking Alu RNA using an 'anti-sense' drug that binds and degrades this toxic substance. ... Ambati's group is preparing to start clinical trials by the end of this year."

Link: http://www.eurekalert.org/pub_releases/2011-02/uok-pdi020311.php

Amongst the folk who talk seriously about aging and longevity, you will find a number of quite different clades characterized by the ideas and ideals held by their members. For example, and drawing with broad strokes:

• Optimistic Dynamists

  The optimists understand the promise of rejuvenation biotechnology - that we stand on the verge of being able to greatly extend the healthy human life span - while remaining aware of the challenges that lie ahead. It will require decades to get to where we're going, but the goal of human agelessness can be attained if we put our shoulders to the wheel.

• Pessimistic Stasists

  A pessimist is dismissive of technological progress, either deliberately or through simply being one of those people who don't spend a lot of time in the consideration of change. Their thoughts on aging are locked to the here and now, caught in the moment. While rigorous in their examination of what is, their projections of what will be are unreliable - their view of aging tomorrow is that it looks much the same as aging today.

• Optimistic Fools

  The optimistic fool believes some or all of the nonsense propagated by the "anti-aging" marketplace, or has deluded himself into thinking that a silver bullet lies just around the corner, some combination of lifestyle and ingested substance if it could just be found. In reality he is only spinning his wheels, just like all who came before him.

Nothing is ever clear cut, of course, and many folk in the community embody aspects of all three clades above, depending on the particular topic at hand. Here, however, is an example of someone firmly in the pessimism camp:

If old age isn't for sissies, then neither is Susan Jacoby's tough-minded, painful-to-read and important book, "Never Say Die," which demolishes popular myths that we can "cure" the "disease" of aging and knocks the "g" right out of the golden years. Forget about those dreams of dropping dead on the tennis court or in a lover's arms at age 95. Such happy endings could happen to us, but the odds are great that they won't, in spite of how frisky we currently feel and in spite of our dedication to a vegetable-eating, nonsmoking, moderate-drinking, daily-exercising lifestyle.

The book covers the ugly realities of degenerative aging in the here and now, but also, as you can see from the quote above, has little good to say about the present and future of medical science. This is a pity, as I think there is great value in puncturing the rosy, populist views of aging put out by the self-empowerment industry, as well as the bubbles most people build around themselves in their efforts not to think about the future of their own aging. Everyone should be afraid of what aging brings - fear is a perfectly rational response to the slow and painful failure of body and mind that lies ahead. If people were less successful at burying this very sensible fear, perhaps they would be more motivated to help advance the cause of longevity science.

People who concern themselves with looking deeply at the here and now often produce works like "Never Say Die" - but a correct analysis of the present only accomplishes half the job of education. It has to be followed up with a correct analysis of change, progress, and the ways in which we can solve the identified problems. Here, that means the engineering of medical technologies to repair the biological damage of aging, something that will happen far more rapidly, I think, if more people looked at the world we live in now with wide open eyes and no illusions.

Even the most widely recognized greatest disasters in human history pale in comparison to natural death. For example, the typhoon that struck Bangladesh in 1970 washed away a million lives. In 1232 AD, Genghis Khan burned the Persian city of Herat to the ground. It took his Mongol horde an entire week to slaughter the 1.6 million inhabitants. The Plague took 15 million per year, World War II, 9 million per year, for half a decade each. The worldwide influenza pandemic of 1918 exterminated less than 22 million people - not even half the annual casualties from natural death. But natural death took 52 million lives last year. We can only conclude that natural death is measurably the greatest catastrophe humankind has ever faced.

From Fast Company: "The mice in the video flickering on his colleague's computer screen were moving their legs. Their back feet trailed behind them from time to time, but the fact that they were walking at all was astounding. Only a few weeks earlier, they'd been paralyzed from the waist down. Then Stupp's team at Northwestern University injected them with made-to-order molecules. Now the mice were trying to run around their cage. ... Those mice were the first living glimpse of the future that Stupp is hoping to accelerate in his role as the director of the Institute for BioNanotechnology in Medicine at Northwestern. It's a future in which molecular self-assembly - where researchers direct molecules to spontaneously combine into ordered structures - will help the body heal itself. ... It wasn't until 1995 that one of his nanotechnology experiments steered him onto an entirely new scientific course. He was trying to make molecules called rodcoils line up side by side to create a large polymer sheet with one side shiny and the other sticky, properties that might make the sheet useful for industrial applications. But something unexpected happened. Instead of forming a single thin membrane, the rodcoils coalesced into trillions of tiny individual structures that looked like mushrooms. Stupp initially wrote off the result as a failure, but he quickly realized that the mushroom-shaped nanoparticles might have a host of advantages. ... What if he could inject the nanomolecules into the bloodstream so they could serve as microscopic vehicles to deliver therapeutic compounds? Even better, what if he could modify the nanomolecules so that they would attract the body's own healing compounds to an injured area, kick-starting the repair process without introducing any foreign cells at all? The 'mushroom' paper Stupp published in 1997 attracted lots of attention, and Northwestern lured the rising star to its materials-science program in 1999. The very next year, Stupp founded IBNAM, the lab he hoped would bring his interdisciplinary ideas to fruition."

Link: http://www.fastcompany.com/node/1715179/print

Another confirmation that your natural longevity is more a matter of your choices than the luck of the draw: "It is often assumed that people with parents who lived to be very old are more likely to live to a grand old age themselves. 'But that's just not true - our study shows that hereditary factors don't play a major role and that lifestyle has the biggest impact,' says professor emeritus Lars Wilhelmsen, referring to the 1913 Men study that formed the basis of the current research. Those who did not smoke, consumed moderate amounts of coffee and had a good socio-economic status at the age of 50 (measured in terms of housing costs), as well as good physical working capacity at the age of 54 and low cholesterol at 50 had the greatest chance of celebrating their 90th birthday. ... We're breaking new ground here. Many of these factors have previously been identified as playing a role in cardiovascular disease, but here we are showing for the first time that they are important for survival in general. The study clearly shows that we can influence several of the factors that decide how old we get. ... The 1913 Men epidemiological study started up in 1963. A third of all male 50-year-olds in Gothenburg were called for a check-up that focused on cardiovascular health. Every ten years since, a new group of 50-year-olds has been called in and those who were already taking part in the study have been given another check-up. This has enabled researchers to follow the development of illnesses in a specific age group, and to compare the health of 50-year-olds in 2003 with that of 50-year-olds in 1963, for example." The choices you make become even more important when we consider the prospects for future medical technology: are you helping to bring about the rejuvenation biotechnology that will extend all healthy human lives, or are you merely sitting on the sidelines and hoping?

Link: http://www.sciencedaily.com/releases/2011/02/110207112539.htm

The age of parochial monolinguism is both coming to an end and stretching out into the foreseeable future. The developing technologies of automated translation will soon enough enable nearly all of us to have our cake and eat it too: to be both fluent in only one language yet speak and understand all languages. In the world of online communities the development of seamless translation tools is already lowering barriers, even though this is a field yet in its infancy. Witness the connections between Russian and English language longevity science advocates, for example, and the ability for any of we Westerners to wander into the network of Russian language blogs and read them in English.

On this theme, let me point you to a French article on the core visions of transhumanism in OWNI. As you can see, the translation automation needs work, but the ability to translate on the fly remains an enormous advance over the human limitations of even the very recent past. Not so long ago it required months of study and then a careful reading to gain the gist of a foreign language article - now the process is instant and the cost insignificant:

An era without aging, disease, and even without shyness or anxiety; an era that would increase the capacity of brain information processing, hopelessly human, too human. This is the future predicted by transhumanism, a movement rooted in the belief of a positive evolution of humanity [under] the influence of technology.

...

Billed as a "disease", death must disappear from the human field and life expectancy tend to infinity. The objective is fundamental, it is located in the top three "to do" transhumanist, says Remy Sussan, journalist [and InternetActu.net author of] a book about Utopias posthuman.

Some go even further, seeking not only to bring down the wall of our ultimate condition of finite being, but also to reverse the effects [to develop methods of rejuvenation].

The contents in detail are less important than the existence of such articles, I think. A significant proportion of the world's population does not speak English, or has no great interaction with the English-language body of work on longevity science. To spread more broadly and gain more support, the ideals of engineered human longevity must become common topics of conversation in languages other than English. Technology will greatly accelerate this process, but it is encouraging to see the signs that it is happening anyway.

Here is an example of the way in which advances in delivery methodology can greatly improve an existing therapy: "Doctors have invented a revolutionary skin spray-gun that heals severe burns within days. The spray-gun which fires stem cells on to the damaged skin has already been used successfully on a dozen patients. Rather than sheets of skin being laboriously grown over a period of a month and applied to the patient, stem cells are harvested from a small patch of healthy skin, put into a solution and sprayed back on to the affected area. The process takes only 90 minutes [and] burns can heal in as little as four days. It eliminates a major flaw of existing burns treatment, the time taken to grow new layers of skin in the lab, during which time patients can die from infection. ... the process involved isolating stem cells from a healthy patch of the patient's skin, putting those cells in a water solution, and then spraying the mixture back on. After being sprayed, the patient's wound is covered with a special dressing that provides glucose, sugar, amino acids, antibiotics and electroytes to the treated area, to provide nutrition and clean the wound until the stem cells get established. ... For Matthew Uram, a police officer from Pennsylvania, the radical technical has already saved his skin. Last July he received severe burns to his face, neck, shoulder, arm and hand after someone threw a cup of petrol on to a bonfire at a party. His hand looked like a 'charred piece of meat', he said. Quickly taken to hospital, he was offered the chance to be one of the first patients to benefit from the skin gun. ... They did it on a Friday, and my follow up was that Monday and the burns unit said it was completely healed."

Link: http://www.telegraph.co.uk/health/healthnews/8302720/Spray-on-skin-developed-for-burns-victims.html

A look at what might be accomplished in the years ahead: "In work that could jumpstart the promising field of cell therapy, in which cells are transplanted into the body to treat a variety of diseases and tissue defects, researchers [have] engineered cells that could solve one of the key challenges associated with the procedure: control of the cells and their microenvironment following transplantation. ... the team reports creating tiny internal depots within human mesenchymal adult stem cells, which among other functions are key to the generation of several tissues. These depots can slowly release a variety of agents to influence the behavior of not only the cells containing the depots, but also those close to them and even much farther away. The team demonstrated this by prompting mesenchymal stem cells to differentiate into the cells that make bone. ... This work could allow programmable cell therapies where the cell or the agent is the therapeutic. For example, depots containing specific agents could enhance cell survival or expression of a particular growth factor. Cells could also be used as a delivery vehicle to shuttle drugs to target tissues that may be useful to accelerate tissue regeneration, or to deliver chemotherapeutics to tumors while minimizing systemic side effects. ... Ten to fifteen years from now, people will visit cell infusion centers to receive routine therapy for multiple diseases and tissue defects. ... For example, a person who has had a heart attack could be infused with cells that could help stimulate regeneration of new heart cells to replace those that have died and prevent eventual heart failure."

Link: http://www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?PageID=804

I have to say that I agree with this fellow when he makes the following point:

"It is my contention here," Ball writes, "that all of the current debates about human embryo research, stem cells, cloning, genetic modification, and bioethics and biotechnology generally, regardless of whether they have any direct link to the creation of artificial humans, cannot be interpreted without understanding the cultural history of that idea and its relation to themes of 'naturalness'. Only by examining the old myths, legends and stories and the ways that they have been modified and mutated by the ages can we grasp the fears and preconceptions that teem beneath the surface of these discussions."

Do people mistrust what their legends and tall tales tell them to be wary of, or does myth, ancient and modern, merely reflect a deeper set of human viewpoints? I suspect a little of both. The article quoted above looks primarily at the biotechnology of building humans, but our grand cultural heritage of stories is also of great importance when it comes to longevity science. We are headed towards the development of ways to defeat aging - and eliminate the consequent frailty and death by age-related disease - and yet so many people and so many myths welcome and romanticize aging and death.

You may or may not be familiar with the Monomyth, but it should nonetheless be obvious that tales which reflect widely shared aspects of the human condition have a great and enduring power. Coming of age, attaining independence, romantic entanglements, challenge and adversity, victory over the odds - and an end to the tale in aging and death. We might say that every story is the story of the Fall: the golden past, the imperfect present, the uncertainty ahead. This is a mirror held to human lives as our millennia-long culture knows them: an age of health and triumph followed by a slow, knowing decline into the darkness we know nothing of. Aging and death are potent ingredients for authors, playwrights, and theologians, and were no less potent for the elders and shamans who came before them.

"Every story is the story of the Fall" - except the one that matters, the one we're all writing together with quills of science, will and toil in the real world. That story is a grand arc of irresistible rise, of the defeat of obstacles and surpassing of limitations to our true potential. But you wouldn't know it from the myths that we find most comforting, as illustrated by their widespread nature.

The tales that audience members like will prosper, and this has always been the case, all the way back to fur-clad audiences of a few dozen, cave-dwellings, and burning branches to ward off the cold. Stories evolve, their characters and plot points like genes, and the relentless evolution of stories under the selection pressure of audience approval has given us a vast body of legends whose plots appeal viscerally to nearly every human. In turn, bodies of myth also serve as a form of education, still widely used by tutors, parents, and elders to teach their children - directly or indirectly - what it means to be human in their society. What do people do to survive and prosper? How does life progress? What are the rightful ways to act towards one another? And so forth.

This is an age of progress and biotechnology. Yet we folk who might be the first ageless humans stand atop a bone mountain. Its slopes are the stories of the dead, created, told, and appreciated by people who knew their own mortality. It is an enormous, pervasive heritage, forged by an army of billions, and no part of our culture or our endeavors is left untouched by it. This is one part of the hurdle we must overcome as we strive to convince people that a near future of rejuvenation biotechnology is plausible, possible, and desirable.

From the MIT Technology Review: "Starting this month, a new European trial aims to determine whether stem cells harvested from a person's own fat, delivered shortly after a heart attack, could prevent some of the cardiac muscle damage that results from blocked arteries. During a heart attack, blood vessels that deliver blood to the heart muscle are blocked, and the lack of oxygen slowly kills the tissue. San Diego-based Cytori Therapeutics has developed a treatment that aims to prevent much of that muscle damage before it starts. It works by injecting a concentrated slurry of stem cells and other regenerative cells isolated from the patient's body directly into the heart's main artery within 24 hours after an attack. ... Time is muscle. The quicker you get in, the better. You can't do anything about dead tissue, but tissue that's bruised and damaged - that's revitalizable. If you can get new blood flow in there, that tissue comes back to life. ... fat tissue has its own population of stem cells that are more easily accessible and far more abundant than the ones in bone marrow. A typical sample of bone marrow yields about 5,000 stem cells; a sample of fat, gathered quickly through liposuction, can provide up to 200 times that amount. ... Fat tissue has been used for years by very astute surgeons, who just pulled pieces of fat into areas that weren't healing well. All the data so far has shown that these cells are safe, but beyond that, what are these cells doing? We just don't know. ... Cytori began a large-scale trial this month and hopes to test the procedure on 360 patients. The company aims to start large-scale clinical trials on heart attack patients in the United States by 2014 and on patients with chronic heart failure even earlier than that."

Link: http://technologyreview.com/biomedicine/32229/

Via EurekAlert!: "A constellation of different stem cell populations within our skin help it to cope with normal wear and tear. By constantly proliferating, the stem cells allow skin to replenish itself, allowing each cell to be replaced by a new one about once a month. But the normal cycle of division and death within one or more of these stem cell types can sometimes be derailed by genetic mishaps. Such events are believed to spawn carcinomas and other deadly skin cancers ... [researchers] have now unmasked a long sought stem cell origin of carcinoma and identified the genetic lesions occurring within these cells that spur them on to malignancy. ... increased activity of a powerful oncogene called Ras combined with overly exuberant activity of a protein called ΔNp63α, stimulates the population of skin stem cells that produce keratin 15 - one of many keratin proteins found in the skin - promoting carcinoma development. ... When cells in the skin or anywhere else in the body sense a potentially cancer-causing threat such as an activated oncogene like Ras - which speeds up cell division - the cells cope by slamming on the brakes to trigger a process called senescence. This is a tumor-suppressive mechanism that halts cell division while allowing cells to stay metabolically active. ... Unfortunately there are a number of genetic events that can bypass senescence and push a cell down the road towards cancer."

Link: http://www.eurekalert.org/pub_releases/2011-02/cshl-csu020111.php

Over the past few years, researchers have designed and carried out interesting and ingenious experiments that try to narrow down which of the biological effects of calorie restriction are important when it comes to the resulting benefits to health and longevity. That calorie restriction notably lengthens healthy life span in almost all species tested to date is beyond doubt: eat less while still obtaining the necessary nutrients for survival and live longer as a consequence. The challenge for the scientific community is that the practice of calorie restriction changes an enormous range of metabolic processes and measures: levels of visceral fat tissue, expression patterns of genes known to be involved in aging, cell cycle behavior, body temperature, and so on down a long, long list. All of these factors are interdependent, and very hard to change in isolation of one another.

So what to do? The answer is to design and run experiments such as this one, and step by step aim at narrowing the field:

Calorie restriction (CR) reduces the rate of cell proliferation in mitotic tissues. It has been suggested that this reduction in cell proliferation may mediate CR-induced increases in longevity. The mechanisms that lead to CR-induced reductions in cell proliferation rates, however, remain unclear.

To evaluate the CR-induced physiological adaptations that may mediate reductions in cell proliferation rates we altered housing temperature and access to voluntary running wheels to determine the effects of food intake, energy expenditure, percent body fat and body weight on proliferation rates ... We found that ~20% CR led to a reduction in cell proliferation rates in all cell types. However, lower cell proliferation rates were not observed with (a) reductions in food intake and energy expenditure in female mice housed at 27°C, (b) reductions in percent body fat in female mice provided running wheels, or (c) reductions in body weight in male mice provided running wheels, compared to ad libitum-fed controls. In contrast, reductions in insulin-like growth factor-1 were associated with decreased cell proliferation rates.

Taken together, these data suggest that CR-induced reductions in food intake, energy expenditure, percent body fat and body weight do not account for the reductions in global cell proliferation rates observed in CR. In addition, these data are consistent with the hypothesis that reduced cell proliferation rates could be useful as a biomarker of interventions that increase longevity.

It is interesting that the hot environment CR mice have this distinctive difference in cellular behavior from those raised in a normal environment. The results that point at cell proliferation rates as something peculiar to the core processes of CR rather than any of its secondary effects, such as weight loss, are also interesting. It would be perhaps enlightening to revisit the twenty or more methods known to extend mouse life span and see what they are all doing to cell proliferation rates. If it turns out that a simple measurement could be used to quickly quantify the prospects of any potential new therapy to slow down the aging process, that would be a big deal.

Another item worth noting is the investigation of drugs that can slow cell proliferation - the cancer research community has developed a few of these, but it is a long way from here to something that could be made safe to give to healthy people. All such efforts are made challenging by the enormous complexity of metabolism: changing it safely is very hard, and changing any one aspect of metabolism in isolation is next to impossible.

From KurzweilAI.net: "New research [demonstrates] the capability of tissue-engineered vascular grafts that are immediately available at the time of surgery and are less likely to become infected or obstructed. A surgeon could pull a new human vein off the shelf for use in life-saving vascular surgeries.The bioengineering method of producing veins shows promise in large- and small-diameter applications, such as for coronary artery bypass surgery and for vascular access in hemodialysis. ... This new type of bioengineered vein allows them to be easily stored in hospitals so they are readily available to surgeons at the time of need. Currently, grafting using the patient's own veins remains the gold standard. But, harvesting a vein from the patient's leg can lead to complications, and for patients who don't have suitable veins, the bioengineered veins could serve as an important new way to provide a coronary bypass. ... In this research, scientists generated bioengineered veins in a bioreactor - a device designed to support a biological environment - and then stored them up to 12 months in refrigerated conditions. The bioengineered veins, 3 millimeters to 6 millimeters in diameter, demonstrated excellent blood flow and resistance to blockage in large animal models for up to a year. ... Not only are bioengineered veins available at the time of patient need, but the ability to generate a significant number of grafts from a cell bank will allow for a reduction in the final production costs, as compared to other regenerative medicine strategies. While there is still considerable research to be done before a product is available for widespread use, we are highly encouraged by the results outlined in this paper and eager to move forward with additional study."

Link: http://www.kurzweilai.net/bioengineered-veins-could-help-patients-needing-bypass-surgery-dialysis

Damage to our mitochondrial DNA is one of the root causes of aging, and here is a specific example of such damage associated with an age-related condition - all the more reason to aggressively fund repair strategies such as protofection and mitoSENS. From the paper: "Mitochondrial DNA damage may be associated with age-related diseases, such as age-related macular degeneration (AMD). The present study was designed to test whether the frequency of mitochondrial DNA (mtDNA) damage, heteroplasmic mtDNA mutations, and repair capacity correlates with progression of AMD. ... Macular and peripheral RPE cells were isolated and cultured from human donor eyes with and without AMD history. The stages of AMD were graded according to the Minnesota Grading System. ... To test the mtDNA repair capacity, cultured RPE cells were allowed to recover for 3 and 6 hours after exposure to H(2)O(2) and then repair assessed by quantitative PCR. The levels of human OGG1 protein, which is associated with mtDNA repair, were analyzed by Western Blot. ... Our study showed that mtDNA damage increased with aging, and more lesions occurred in RPE cells from the macular region relative to the periphery. Furthermore, mtDNA repair capacity decreased with aging, with less mtDNA repair capacity in the macular region compared with the periphery in samples from aged subjects. Most interestingly, the mtDNA damage is positively correlated with the grading level of AMD, while repair capacity is negatively correlated. In addition, more mitochondrial heteroplasmic mutations were detected in eyes with AMD. ... Our data show macula-specific increases in mtDNA damage, heteroplasmic mutations and diminished repair that are associated with aging and AMD severity."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21273542

Recent analysis of a bisphosphonate treatment for osteoporosis, or age-related loss of bone mass and strength, has turned up an intriguing finding - the treatment considerably improves life expectancy in the recipients. It's not often that an effect of this magnitude turns up out of the blue in humans in this day and age:

Australian clinical researchers have noted an extraordinary and unexpected benefit of osteoporosis treatment - that people taking bisphosphonates are not only surviving well, better than people without osteoporosis, they appear to be gaining an extra five years of life. ... Out of a total cohort of around 2,000, a sub-group of 121 people were treated with bisphosphonates for an average of 3 years. When compared with other sub-groups taking other forms of treatment, such as Vitamin D (with or without calcium) or hormone therapy, the longer life associated with bisphosphonate treatment was marked and clear.

...

While the results seemed surprisingly good, they are borne out by the data - within the limitations of any study - and appear to apply to men as well as women. When we first looked at the figures, we thought that there had to be a fallacy, that we were missing something. One of the most obvious things might be that these are people who seek medical attention, so may be healthier and live longer. So we compared the bisphosphonate group with people taking Vitamin D and calcium or women on hormone therapy. The comparison against these other groups of similarly health-aware people simply confirmed that our results were not skewed by that factor.

In a group of women with osteoporotic fractures over the age of 75, you would expect 50% to die over a period of five years. Among women in that age group who took bisphosphonates, the death rate dropped to 10%. Similarly, in a group of younger women, where you would expect 20-25% to die over 5 years, there were no deaths.

The mechanism by which this extension of healthy life occurs is unknown. The authors of the study offer a guess relating to heavy metal deposition in bone tissue - but it is only a guess and frankly doesn't seem all that plausible, given all of the other potential candidate systems that might be influenced by bisphosphonate therapy. Whatever the mechanism, I can see this discovery being a tremendous encouragement for the industries of people who believe that great good can be achieved for human longevity through the old style development of injections, pills, and other forms of traditional medicine.

I think they're all wrong, and that the future of longevity lies in other directions - but this sort of discovery does tend to undermine that position. It's all a utilitarian and economic argument: if someone today discovers a cheap way to boost life expectancy by five years for most of the population, then obviously that is worth developing out into a product. But is it worth spending billions hunting for the possibility of a nebulous old-style medical therapy that can boost life expectancy by five years versus spending that same amount on the development of rejuvenation biotechnology? No, of course not.

Given the present systems of regulation in place in much of the world, it seems unlikely that anyone in the mainstream research community will run the obvious follow-up study on healthy older folk - despite, I'm sure, there being no shortage of volunteers should such a study take place. There is a considerable institutional and regulatory bias against the investigation and development of any form of therapy not targeted against designated diseases, and aging is not a designated disease.

From the SENS Foundation: "The degenerative aging of the immune system is responsible for an enormous burden of disease and disability, from the pain of recurrent Herpes zoster and postherpetic neuralgia, to elevated rates of chronic urinary tract infections, to complications in wounds, pressure sores, ulcers, and surgical incisions. Most prominently, it underlies the meteoric rise in mortality from respiratory infections with age: influenza, pneumonia, and septicemia rise from being negligible causes of death in healthy middle-aged adults in the USA, to emerge amongst the top 10 causes of death in adults over the age of 55, with mortality rates climbing with each successive year of aging. And in addition to increasing the morbidity and mortality specifically attributable to particular infections, the dysregulation of immune function by immunosenescence is widely acknowledged to exacerbate multiple chronic age-related illnesses, and to contribute to functional decline and frailty in aging people. While vaccine manufacturers and public health officials have rightly advocated for expansion of population vaccine coverage as a measure to blunt the burden of infectious disease in the elderly, the effectiveness of this strategy is itself limited by immunosenescence, which progressively diminishes the adaptive immune system's response to vaccination with age ... The solution to age-related suffering and death from specific infections, autoimmunity, and inflammation is the application of rejuvenation biotechnology to the aging immune system itself. The clearest and longest-established contributor to immune senescence is the decline in adaptive immunity mediated by T lymphocytes, the biomedical remediation of which has therefore been the focus of SENS Foundation's investments in immunological rejuvenation research."

Link: http://www.sens.org/node/1901

It can be argued that advanced glycation endproducts play an important role in Alzheimer's disease, as well as other degenerations of aging. Here is a review paper on the topic: "Alzheimer's disease (AD) is the most common dementia disorder of later life. Although there might be various different triggering events in the early stages of the disease, they appear to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. Here, we review the hypothesis that advanced glycation end products (AGEs), which reflect carbonyl stress, an imbalance between the production of reactive carbonyl compounds and their detoxification, can serve as biomarkers for the progression of disorder. AGE modification may explain many of the neuropathological and biochemical features of AD, such as extensive protein cross-linking shown as amyloid plaques and neurofibrillary tangles, inflammation, oxidative stress and neuronal cell death. Although accumulation of AGEs is a normal feature of aging, it appears to be significantly accelerated in AD. We suggest that higher AGE concentrations in brain tissue and in cerebrospinal fluid might be able to distinguish between normal aging and AD." Effective removal of AGEs through strategies such as bioremediation is one part of the SENS research agenda.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21275816

If you grew up reading science fiction from the golden era of pulp and wide-eyed planetary optimism, then you've no doubt noticed that you are more or less already living in the shining future those authors wrote about. We ended up with computing power and biotechnology far beyond their imagining rather than near-free energy and space travel, but the results are just as impressive. On the whole we're better off with the direction taken by reality over fiction: massive low cost energy generation and distribution technologies wouldn't do anything to slow down the aging process.

Following the latest cancer research news, I'm generally struck by just how much a lot of it sounds like the engineer-oriented science fiction inventions of yesteryear. For example, researchers can now place homing nanoparticles in the brain that destroy tumor tissue - and only tumor tissue - when heated by low-intensity radiation beams. Scientists can also also filter out metastatic cancer cells from the bloodstream using a range of techniques. Neither of these approaches would look out at all out of place in a Lensman novel. But nonetheless here we are:

New Treatment Option For Ovarian Cancer

In an article published in the January issue of the journal Nanomedicine, the researchers suggested the use of an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumours. The scientists have formed a startup company and are working with a medical device firm to design a prototype treatment system that would use magnetic nanoparticles engineered to capture cancer cells. Added to fluids removed from a patient's abdomen, the magnetic nanoparticles would latch onto the free-floating cancer cells, allowing both the nanoparticles and cancer cells to be removed by magnetic filters before the fluids are returned to the patient's body.

Early Tests Find Nanoshell Therapy Effective Against Brain Cancer

Rice University bioengineers and physician-scientists at Baylor College of Medicine and Texas Children's Hospital have successfully destroyed tumors of human brain cancer cells in the first animal tests of a minimally invasive treatment that zaps glioma tumors with heat. The tests involved nanoshells, light-activated nanoparticles that are designed to destroy tumors with heat and avoid the unwanted side effects of drug and radiation therapies.

...

Gold nanoshells, which were invented by Rice researcher Naomi Halas in the mid-1990s, are smaller than red blood cells. Nanoshells are like tiny malted milk balls that are coated with gold rather than chocolate. Their core is nonconducting, and by varying the size of the core and thickness of the shell, researchers can tune them to respond to different wavelengths of light. Houston-based biomedical firm Nanospectra Biosciences, which holds the license for medical use of Rice's nanoshell technology, began the first human clinical trial of nanoshell phototherapy in 2008.

We no longer live in the world our parents grew up in, for all that it's easy to forget just how far medical science has progressed in our lifetimes. This progress is speeding up; the new and better is arriving ever faster. Somewhere out there in the future is a cancer with your name on it, and as we live ever longer thanks to other advances in medicine, it will become very important that the next generation of cancer therapies be made highly reliable and very safe.

Macromolecules are parts in our cellular machinery, themselves large and complex arrangements of atoms. Some of these macromolecules are short lived and rapidly recycled, but many are not. They are vulnerable to damage in ways that can significantly alter their behavior - such as by reacting with free radicals generated by mitochondria, or being glued together into advanced glycation end-products. Here is a paper offering some thoughts on what that means for human aging: "A number of tissues and organs in the human body contain abundant proteins that are long-lived. This includes the heart, lung, brain, bone and connective tissues. It is proposed that the accumulation of modifications to such long-lived proteins over a period of decades alters the properties of the organs and tissues in which they reside. Such insidious processes may affect human health, fitness and ultimately may limit our lifespan. The human lens, which contains proteins that do not turnover, is used to illustrate the impact of these gradual deleterious modifications. On the basis of data derived from the lens, it is postulated that the intrinsic instability of certain amino acid residues, which leads to truncation, racemisation and deamidation, is primarily responsible for the age-related deterioration of such proteins. Since these post-translational modifications accumulate over a period of many years, they can only be studied using organisms that have lifespans measured in decades. One conclusion is that there may be important aspects of human aging that can be studied only using long-lived animals." With or without further study, researchers know that these forms of damage exist and know how best to proceed to fix them - it's just a matter of funding and the will to proceed.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21272671

Yet another reason to keep up with your exercise routine: "A new study shows that one year of moderate physical exercise can increase the size of the brain's hippocampus in older adults, leading to an improvement in spatial memory. [This] is considered the first study of its kind focusing on older adults who are already experiencing atrophy of the hippocampus, the brain structure involved in all forms of memory formation. ... The scientists recruited 120 sedentary older people without dementia and randomly placed them in one of two groups - those who began an exercise regimen of walking around a track for 40 minutes a day, three days a week, or those limited to stretching and toning exercises. Magnetic resonance images were collected before the intervention, after six months, and at the end of the one-year study. The aerobic exercise group demonstrated an increase in volume of the left and right hippocampus of 2.12 percent and 1.97 percent, respectively. The same regions of the brain in those who did stretching exercises decreased in volume by 1.40 and 1.43 percent, respectively. Spatial memory tests were conducted for all participants at the three intervals. Those in the aerobic exercise group showed improved memory function, when measured against their performance at the start of the study, an improvement associated with the increased size of the hippocampus. The authors also examined several biomarkers associated with brain health, including brain-derived neurotrophic factor (BDNF), a small molecule that is involved in learning and memory. They found that the increases in hippocampal size were associated with increased amounts of BDNF. ... We think of the atrophy of the hippocampus in later life as almost inevitable. But we've shown that even moderate exercise for one year can increase the size of that structure. The brain at that stage remains modifiable."

Link: http://www.eurekalert.org/pub_releases/2011-01/uoia-mae012611.php