Fight Aging!

FIGHT AGING! NEWSLETTER
June 3rd 2013

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

• Civil Disobedience and DIYbio
• What Causes the Lack of Funding for Rejuvenation Research?
• Bracketed by Billionaires
• Stem Cells as Drug Factories
• Considering the Regenerative Signals Emitted by Transplanted Stem Cells
• Discussion
• Latest Headlines from Fight Aging!
  • A Bioprosthetic Heart
  • Exercise Versus Peripheral Artery Disease
  • Stem Cell Transplants for Leukemia Showing Improved Outcomes
  • An Interview With Dmitry Itskov
  • Less Cancer in Long-Lived Families
  • Fat Tissue Density Predicts Mortality
  • Alzheimer's Drug Candidate Provides Benefits in Mice Without Clearing Amyloid Plaques
  • Looking at the Commercial Development of Rapamycin
  • Healthspan Campaign
  • Stephen Cave Doesn't Get It

CIVIL DISOBEDIENCE AND DIYBIO
https://www.fightaging.org/archives/2013/05/civil-disobedience-and-diybio.php

From a point of view of materials and time it is not costly to set up a home laboratory for the purposes of synthesizing chemical compounds or even perform simple procedures in biotechnology - raising bacteria, assaying genes in lower animals, and so on. It is, however, illegal to just forge ahead and do this in most US states or in much of Europe due to the many prosaic, stupid laws that encrust the body politic. Such laws hang around for long after they stop serving whichever special interest wrote them and bribed politicians to pass them. Then there are the cases of mass hysteria that become written into law and continue onward for decades no matter how much harm they cause, such as the drug war.

It is in fact the drug war, and not the normal background level protectionism of licenses and zoning, that turns DIYbio, amateur chemistry and other similar citizen science activities into an expensive and risky endeavor. It should be cheap, but the cost is now all in the risk. The state has shown great willingness to smash first and ask questions later, if at all, and this leads to things like reagent providers only selling to registered labs, requirements to register all glassware, and raids conducted on people who followed all the rules - because the left hand doesn't care what the right hand said, and local police departments make out like bandits from confiscation and auction of assets belonging to those merely accused of breaking laws. Where there are incentives, there will be those who follow the incentives, and the incentives today are very much aligned with less citizen science and more police accusation.

The present state of medical regulation is every bit as bad as the drug war, and indeed very much influenced by it when it comes to thing like painkillers. The massive body of law concerning medicine and life science research accomplishes numerous iniquities beyond ensuring that people suffer more pain at times when drugs could prevent that suffering: it slows development; it makes therapies much more expensive; it eliminates whole regions of development by making them too costly to attempt; it prohibits some classes of therapy by fiat, such as those that aim to treat degenerative aging; it makes it illegal for a dying person to make an educated decision about trying an experimental therapy. And so forth.

At some point the massive wall of laws, all of the forbiddances telling people that they cannot try to make their lives better, will run headlong into the fact that it is becoming ever cheaper to synthesize drugs and the basis for therapies in a home laboratory. All it takes is knowledge and the willingness to undertake civil disobedience: to disregard a law because it is evil and unjust. It has to be said that near every law that touches on medicine in this day and age is evil and unjust, and the costs they impose in their aggregate cause great pain, suffering, and death. What might have been accomplished without the ball and chain of regulation is invisible, however, and therefore easily waved away by those who claim that regulation is necessary. Everyone takes the present state of affairs as the way things are and looks little past it.

Unlike recreational drugs, it is clear that the costs and the benefits for manufacturing your own medicine are not yet at the point of spurring people to action at the level of small chemistry or biotech laboratories. The knowledge is still too specialized, the complexity of the work too great, and the benefits too narrow. This will change, however, and think it will largely change on the benefit side of the equation. For example, consider mitochondrially targeted antioxidants like SS-31 and SkQ compounds: synthesizing them is an exercise in organic chemistry that is many steps in sophistication above the bucket chemistry of a recreational drug laboratory, but I have to imagine that there will be a market for these things once the public starts to appreciate that they seem to have significant effects on aging tissue. SS-31 produces endurance benefits in older mice when tested, and that's probably a draw if it does the same for people. The athletics community certainly includes an underground of experimental biochemistry, one of the consequences of all the money floating around there.

Targeted antioxidants shown to reverse some aspects of aging and extend life in mice are a trivial exercise in comparison to what is coming down the line, however. It won't be too many years from now before researchers can describe exactly how to repair and replace damaged mitochondria, construct infused enzyme solutions that destroy specific metabolic waste products that contribute to aging, and so forth. The future of medicine to treat aging and extend life will consist of a whole range of precisely designed proteins like the waste-product-chewing enzymes that can be manufactured in an appropriately equipped biotech lab. The cost of materials will continue to fall, the knowledge needed to perform the work will continue to disseminate, and when the upside of civil disobedience is rejuvenation and more years of healthy life then there will be a whole lot more civil disobedience.

In actual fact, I think that the scenario of distributed scofflaw medical manufacture will happen along the way, long before SENS-like rejuvenation biotechnology is at a point where portions of it could - in theory - be performed in a sufficiently well equipped home laboratory. Something better than SS-31 will emerge, or at least something better equipped to catch the public imagination, and grey and black markets will bloom. I'm looking forward to it: the present system of medical regulation is ugly, repressive, and costs lives: the sooner it collapses in the face of ubiquitous disregard the better.

WHAT CAUSES THE LACK OF FUNDING FOR REJUVENATION RESEARCH?
https://www.fightaging.org/archives/2013/05/what-causes-the-lack-of-funding-for-rejuvenation-research.php

There isn't a great deal of funding for research into aging in comparison to the rest of medicine. It is greatly underfunded given its importance in biology, and this continues to be the case even after a decade or two of growing interest. Research into the manipulation of aging is a tiny field within aging research - most aging research is still a matter of gathering data. Lastly, research aimed at treating and reversing aging is a tiny fraction of work on manipulation of aging. The US National Institute on Aging has a $1 billion yearly budget, and might be a third of spending in the US on aging research; the SENS Research Foundation, which is arguably the only group managing research programs to realize plausible means of rejuvenation, has a yearly budget of $3 million.

This is what entrepreneurs, ever optimistic, call "a growth opportunity." Astronomical budgets are dedicated to medicine, merely vast budgets for amassing information about aging, and infinitesimal budgets are all that is presently available to stop the suffering, pain, death, and expense caused by aging. Rejuvenation research must grow if we are to see significant progress before we age to death.

Why is the budget for rejuvenation research tiny? My intuitive response to that is that is a combination of (a) that it has only recently become plausible to work on building therapies capable of rejuvenation, somewhere within the last 20 years, (b) few people know anything about the science that supports the plausibility of treating and reversing aging, and (c) few people care enough about living longer to do anything about it. Plus I might argue that the "anti-aging" marketplace sidetracks people into useless activities, while aggressively spreading misinformation about how we might go about extending life.

I noticed a post at Immortal Life that argues slightly differently: the root of not having enough funding is that we are failing to raise it. That we are bad at advocacy, or at least insufficient in numbers, and need to become better. It's an interesting position: are we terrible advocates by virtue of not having achieved the sweeping gains that, say, the AIDS advocacy community managed in a few short years in the 1980s? Or are we acceptably good at what we do but still early in the game - where the trajectory is more like that of the decades preceding the establishment of today's massive cancer research establishment?

Radical Life Extension's Problem isn't Lack of Funding - it's Weak Advocacy

When asked what the biggest bottleneck for Radical or Indefinite Longevity is, most thinkers say funding. Some say the biggest bottleneck is breakthroughs and others say it's our way of approaching the problem (i.e. seeking healthy life extension as opposed to more comprehensive methods of indefinite life-extension), but the majority seem to feel that what is really needed is adequate funding to plug away at developing and experimentally-verifying the various, sometimes mutually-exclusive technologies and methodologies that have already been proposed. I claim that Radical Longevity's biggest bottleneck is not funding, but advocacy.

This is because the final objective of increased funding for Radical Longevity and Life Extension research can be more effectively and efficiently achieved through public advocacy for Radical Life Extension than it can by direct funding or direct research, per unit of time or effort. Research and development obviously still need to be done, but an increase in researchers needs an increase in funding, and an increase in funding needs an increase in the public perception of RLE's feasibility and desirability.

There is no definitive timespan that it will take to achieve indefinitely-extended life. How long it takes to achieve Radical Longevity is determined by how hard we work at it and how much effort we put into it. More effort means that it will be achieved sooner. And by and large, an increase in effort can be best achieved by an increase in funding, and an increase in funding can be best achieved by an increase in public advocacy. You will likely accelerate the development of Indefinitely-Extended Life, per unit of time or effort, by advocating the desirability, ethicacy and technical feasibility of longer life than you will by doing direct research, or by working towards the objective of directly contributing funds to RLE projects and research initiatives.

I'd qualify that last point by suggesting that an hour of advocacy is only better than giving an hour of your wages to the SENS Research Foundation if that hour of advocacy actually results in more money showing up for SENS projects. I believe I'm still ahead of the game by that measure, but I'm nowhere near as certain of that as I'd like to be. It really does all come down to money at this precise point in time, now that there exists an established rejuvenation research program that can soak up many more millions of dollars with ease. With enough money the next five to ten years will produce such amazing results in the laboratory that using research to generate publicity looks like a better option than using publicity to generate funds for research.

But of course no-one is going to turn down publicity-generated funds should someone figure out how to make that work well in the intervening time. Over the long haul, it is the case that publicity and science have to move together, it's just here and now that resources for research look to have a better value than resources for publicity.

As an aside, and while we're on the subject of money, Immortal Life appears to be run by the same folk who managed Transhumanity.net before it was transferred to the Zero State initiative. The site as a whole illustrates why it's hard to build a for-profit single topic site for radical life extension: there is no technology available today that can achieve that goal, so the only legitimate flow of money is towards research. Everyone in the interested marketplaces that might pay the site owner to run ads or ads-disguised-as-content are in the business of selling dreams, lies, and other things that don't really matter. So if you focus on money, you end up slipping away from the ongoing research that matters and towards supplement pills and other dead ends. This, at least, has been the historical and ongoing outcome of these efforts - but that doesn't mean that it always must be. There are, after all, reputable general interest futurist sites, so you'd think there are some methodologies that might work without having to become a shill for the "anti-aging" market and supplement sellers. I'm just appropriately skeptical, given the past.

BRACKETED BY BILLIONAIRES
https://www.fightaging.org/archives/2013/05/bracketed-by-billionaires.php

Billionaires are just like you and me, but with deeper pockets. They will age and die on the same schedule as the rest of us, as future life span is almost entirely determined by the pace of progress in medical science and the availability of modern medicine is very flat. Within a few years of any new medical technology arriving in the clinic it settles to a price that can be widely afforded. If you're sixty and sitting on your retirement fund then there's very little in the way of medicine that a billionaire could afford but you can't. The billionaire can afford a dedicated hospital with new wall murals, but the therapies are exactly the same as those you'd buy for yourself: a stem cell transplant or infusion of enzymes doesn't care about the size of your bank balance.

Here is another way in which billionaires are just like the rest of us: very few of them care enough about aging to death to do anything about it. Or they don't believe that anything can be done, or they are not up to speed with the present state of longevity science and the potential of SENS-style rejuvenation biotechnology, or any one of the other reasons offered up whenever people's attitudes towards aging are discussed.

Just as a small fraction of the public care enough about aging to do something about it - ranging from donating a little money or time to organizations like the Methuselah Foundation or SENS Research Foundation all the way up to quitting work, going back to school, and becoming a researcher - a small number of billionaires also take steps. Again, these range from modest donations through to the hard right turn in life to take a different path and focus fully on the problem of aging. Unfortunately of these folk only one is a patron for SENS, while the others are focus on different areas that are, ultimately, not particularly relevant to our future longevity for one reason or another. Such is life.

So you might say that SENS, the research program we'd like to see gain a vocal zealot willing to spend hundreds of millions of dollars, is bracketed by billionaires. Interested billionaires in fields just off to the left, interested billionaires in fields just off to the right. The optimistic view is that yes, it's just a matter of time until someone is convinced and takes the plunge - because, clearly, some people are thinking along parallel lines and thus we should expect there to be more in the future.

Larry Ellison

Of all the mentioned billionaires, Ellison comes closest to the right direction, but in many ways he's the least interested. He established the Ellison Medical Foundation in the 1990s to explore aging - not because longevity is a passion, but rather because aging research is a good source of intellectual and organizational challenges in the field of molecular biology. Molecular biology was the object, and aging research the happenstance outlet. So the end result is effectively an extension of the National Institute on Aging, and therefore focused on work that has little relevance to extending life. The majority of NIA-funded research is a matter of investigation, not intervention.

Peter Thiel

Thiel has funneled some millions of dollars into SENS research and is to be commended for doing so in a very public way at a time when you could still be ridiculed for it. He is also engaged in producing a broader environment of philanthropy within the networks he can reach with the aim of promoting greater investment and interest. SENS is just one of many radical projects he backs, however, a single part of the large jigsaw puzzle that is Thiel's attempt to influence the building of a better future.

David Murdock

Murdock's interest with longevity extends only so far as its intersection with diet and clean living. He has founded a research institute, the North Carolina Research Campus - and I think that if you manage to create a legacy of scientific research then it's hard to say you went far wrong in life. The focus here is on diet, however, which is very beneficial for health (such as via calorie restriction) but most likely of limited utility when it comes to extending human life. You can't eat your way to reaching 100 years of age with any certainty, and most people with superbly healthy lifestyles nonetheless age to death by 90. The future of longevity is modern medicine.

John Sperling

Sperling has funded a number of ventures of relevance to medicine and health, with a slant on longevity that is similar to the old school "anti-aging" businesses, such as Kronos Optimal Health. These are of no great utility when it comes to extending life: they are simply high end optional health services. At one point Sperling looked set to do much more and talked a good game about longevity, but per Wikipedia he is now more focused on environmental causes than human aging.

Dmitry Itskov

Itskov is taking the hard right turn in life in order to set up and promote his 2045 Initiative: tackle aging by moving out of biology and into machine bodies as soon as possible. He has a vision and is prepared to step up to the plate and put his reputation on the line in order to promote it with the financial muscle available to him. It's only a couple of years into this process, so we shall see how it goes once the initial run has settled down into the slow grind of advocacy, networking, and research funding. But from what we've seen so far, this is the sort of passion for a cause I'd like to see settle onto SENS rather than what looks like a much harder path to eliminate aging.

I'll say this for Itskov: a world in which a billionaire is prepared to openly and loudly back work on machine bodies and artificial minds is a world in which people don't laugh at high net worth individuals who back research into rejuvenation biotechnology. Once someone has planted a flag all the way out there on the field, other people become much more comfortable with what are now less radical gestures. We're somewhere in the middle of a sea change for the public perception of transhumanist technologies: robotics, AI, rejuvenation, and so forth. The cultural space within which people treated these fields as jokes and science fiction is vanishing rapidly, squeezed out by current events.

STEM CELLS AS DRUG FACTORIES
https://www.fightaging.org/archives/2013/05/stem-cells-as-drug-factories.php

The future of medical drugs will largely involve the manufacture of proteins that precisely interact with our biochemistry to achieve specific effects. They will either be existing proteins with a role in regulating metabolism, stem cell activity, immune cell response, and so on, or they will be entirely new nanomachinery intended to produce results that our biology cannot achieve on its own, such as the effective destruction of harmful waste products, for example. These designed proteins will be delivered the old-fashioned way, via injection, for a good many years yet. Ultimately, however, managing the manufacture and the timing and location of protein delivery will move into the body under the control of sophisticated tiny factory machines - mass-produced entities that will in fact bear a great deal of resemblance to cells.

What is a cell, after all, but a flexible protein factory that manages its output in response to the surrounding environment? Why reinvent the wheel when a perfectly functional version is right there to be reverse engineered? Or used as-is, for that matter: present day stem cell therapies are just like future treatments that will deliver tiny mobile drug factories into a patient's tissues. Today's crude cell therapies appear to work because the newly introduced cells are, for a short time at least, manufacturing proteins that change the behavior of local cells. This is a little bit of the future made possible by harnessing existing biological machinery. Researchers can even reach beyond the use of plain cells today, such as by altering stem cells to generate specific desired compounds:

Engineered stem cell advance points toward treatment for ALS

[Researchers] used adult stem cells from human bone marrow and genetically engineered the cells to produce compounds called growth factors that can support damaged nerve cells. The researchers then implanted the cells directly into the muscles of rats that were genetically modified to have symptoms and nerve damage resembling ALS.

In people, the motor neurons that trigger contraction of leg muscles are up to three feet long. These nerve cells are often the first to suffer damage in ALS, but it's unclear where the deterioration begins. Many scientists have focused on the closer end of the neuron, at the spinal cord, but [others] observes that the distant end, where the nerve touches and activates the muscle, is often damaged early in the disease. "We know that the neuro-muscular junction is a site of early deterioration, and we suspected that it might be the villain in causing the nerve cell to die. It might not be an innocent victim of damage that starts elsewhere."

The injected stem cells survived for at least nine weeks, but did not become neurons. Instead, their contribution was to secrete one or both growth factors. "These motor nerve cells have extremely long connections, and replacing these cells is still challenging. But we aim to keep the neurons alive and healthy using the same growth factors that the body creates, and that's what we have shown here."

Cells and cell-like entities are steadily on their way to becoming the dominant tools of medicine. The more that researchers know about cells, the more useful they become in this role. Programmable protein factories in the form of cells or pseudo-cells will ultimately take over from the direct delivery of designed protein machinery in the same way that the creation of designed protein machinery will soon replace the old-fashioned and haphazard process of discovering and testing naturally occurring drugs. This is progress.

CONSIDERING THE REGENERATIVE SIGNALS EMITTED BY TRANSPLANTED STEM CELLS
https://www.fightaging.org/archives/2013/05/considering-the-regenerative-signals-emitted-by-transplanted-stem-cells.php

Enhanced regeneration can result from introducing new stem cells into a patient, and this effect is the basis for a very broad range of first generation transplant therapies. In most cases the benefit doesn't result from the transplanted stem cells setting forth to create replacement cells for damaged tissue. Instead it is caused by chemical signals produced by the transplanted cells: these signals spur native cell populations to take action. So naturally the next step here is for researchers to gain a good enough understanding of stem cell signals to remove the need for cell transplants, replacing them with a therapy based on introducing the signal molecules directly.

It's very hard to say how rapidly this line of research will progress in comparison to the ongoing development of therapies that involve cells, a field in full swing. But in the long term it seems likely that directly adjusting the state and behavior of a patient's native cells will win out over indirect methods. Using the signals may just be another indirect method to be replaced by something better down the line, such as targeted epigenetic engineering that reprograms specific cell populations without going through any of the evolved signal paths.

But that is a way from here, as the use of stem cells in therapy is still two decades away from its peak usage and effectiveness - if we want to take the standard view of fifty year cycles in broad technologies, waxing to full effectiveness and then waning as they are replaced by something better. The cycle may run faster this century: we'll see whether that is the case or not, something that is determined by the degree to which the timing depends on human organization versus technological capacity. The former isn't speeding up, while the latter is.

Meanwhile, here is an open access paper that illustrates the way in which scientists are presently looking at stem cell signals. The research community is clearly on the way towards a range of these signal compounds repackaged and repurposed as drug candidates to induce exceptional regeneration. I expect that line of development will be well underway by the early 2020s.

hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding

Tissue regeneration and maintenance dramatically and invariably decline with age, eventually causing failure of multiple organ systems in all mammals. In muscle, the loss of tissue regeneration with age is thought to be imposed by signaling changes in the satellite stem cell niche, and interestingly, the aging of stem cell niches is to some extent similar between muscle, brain, blood, and other tissues. Our previous work found that human embryonic stem cells (hESCs) produce soluble secreted molecules that can counteract the age-imposed inhibition of muscle regeneration, an "anti-aging" activity that is lost when the hESCs differentiate.

Numerous mitogenic proteins are expressed by hESCs and are known to act through [key regulatory signaling pathways] implicated in the control of adult tissue regeneration. The precise identity of the pro-myogenic factors that are secreted by hESCs and the molecular mechanism of their action in muscle stem and progenitor cells is still work in progress; however, the effects of one of these molecules, FGF-2, was studied here in detail. FGF-2 is known to be secreted by hESCs and is also contained in the growth/expansion medium of embryonic stem cells.

This work builds upon our findings that proteins secreted by hESCs exhibit pro-regenerative activity, and determines that hESC-conditioned medium robustly enhances the proliferation of both muscle and neural progenitor cells. Importantly, this work establishes that it is the proteins that bind heparin which are responsible for the pro-myogenic effects of hESC-conditioned medium, and indicates that this strategy is suitable for enriching the potentially therapeutic factors. Additionally, this work shows that hESC-secreted proteins act independently of the mitogen FGF-2, and suggests that FGF-2 is unlikely to be a pro-aging molecule in the physiological decline of old muscle repair. Moreover, hESC-secreted factors improve the viability of human cortical neurons in an Alzheimer's disease (AD) model, suggesting that these factors can enhance the maintenance and regeneration of multiple tissues in the aging body.

You'll find more on the role of FGF-2 regarding stem cells and aging back in last year's archives. The authors quoted above suggest that past work on FGF-2 can't be the whole picture, based on their observations, and something more complex is taking place - which is the usual story in life science research. Nothing is ever simple.

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

LATEST HEADLINES FROM FIGHT AGING!

A BIOPROSTHETIC HEART
Friday, May 31, 2013
https://www.fightaging.org/archives/2013/05/a-bioprosthetic-heart.php

New approaches to electromechanical artificial hearts involve the replacement of some portions of the machine with tissue, such as the cow heart tissue used in this case. The end result is a more durable apparatus that better interfaces with the body, though it's still the case that artificial heart technology cannot replace a biological heart for the long term:

A new kind of artificial heart that combines synthetic and biological materials as well as sensors and software to detect a patient's level of exertion and adjust output accordingly is to be tested in patients at four cardiac surgery centers in Europe and the Middle East. If the "bioprosthetic" device, made by the Paris-based Carmat, proves to be safe and effective, it could be given to patients waiting for a heart transplant.

In Carmat's design, two chambers are each divided by a membrane that holds hydraulic fluid on one side. A motorized pump moves hydraulic fluid in and out of the chambers, and that fluid causes the membrane to move; blood flows through the other side of each membrane. The blood-facing side of the membrane is made of tissue obtained from a sac that surrounds a cow's heart, to make the device more biocompatible. "The idea was to develop an artificial heart in which the moving parts that are in contact with blood are made of tissue that is [better suited] for the biological environment."

That could make patients less reliant on anti-coagulation medications. The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device. That information is sent to an internal control system that can adjust the flow rate in response to increased demand, such as when a patient is exercising.

EXERCISE VERSUS PERIPHERAL ARTERY DISEASE
Friday, May 31, 2013
https://www.fightaging.org/archives/2013/05/exercise-versus-peripheral-artery-disease.php

Some age-related conditions are greatly impacted by exercise, and a sedentary lifestyle is one of the factors raising the risk of suffering these conditions. Type 2 diabetes is the best known of these, a lifestyle disease that you can actually exercise and diet your way out of if you work at it hard enough. Peripheral artery disease isn't so escapable, being a later stage in the process of deterioration, but exercise is still beneficial to a point comparable to other options for treatment:

Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12 to 15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed.

The presence of PAD predicts a 50% to 1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking approximately five times per week, at a significant intensity that requires frequent rest periods, are most significant.

Preclinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, and mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. [The] benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a lifestyle pattern that includes enhanced physical activity prior to the advance of PAD limitations is the most desirable and beneficial.

Is there a lesson here? Yes: exercise regularly. Don't be sedentary.

STEM CELL TRANSPLANTS FOR LEUKEMIA SHOWING IMPROVED OUTCOMES
Thursday, May 30, 2013
https://www.fightaging.org/archives/2013/05/stem-cell-transplants-for-leukemia-showing-improved-outcomes.php

Researchers recently published a set of encouraging data resulting from the use of stem cell transplants in the treatment of forms of leukemia. Once a particular new technique is adopted in medical practice, further progress is often a matter of steady incremental improvement. Here that improvement is quite considerable over the past decade, a reflection of the pace of medical science in general:

Survival rates have increased significantly among patients who received blood stem cell transplants from both related and unrelated donors. [The] study authors attribute the increase to several factors, including advances in HLA tissue typing, better supportive care and earlier referral for transplantation. The study analyzed outcomes for more than 38,000 transplant patients with life-threatening blood cancers and other diseases over a 12-year period - capturing approximately 70 to 90 percent of all related and unrelated blood stem cell transplants performed in the U.S.

At 100 days post-transplant, the study shows survival significantly improved for patients with myeloid leukemias (AML) receiving related transplants (85 percent to 94 percent) and unrelated transplants (63 percent to 86 percent). At one-year post-transplant, patients who received an unrelated transplant showed an increased survival rate from 48 to 63 percent, while the survival rate for related transplant recipients did not improve. Similar results were seen for patients with acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). In addition to improved survival, the authors note a significant increase in the overall number of patients receiving transplants. Related and unrelated transplant as treatment for ALL, AML, MDS and Hodgkin and non-Hodgkin lymphomas increased by 45 percent - from 2,520 to 3,668 patients annually. This is likely due to the use of reduced-intensity conditioning therapy and a greater availability of unrelated volunteer donors.

AN INTERVIEW WITH DMITRY ITSKOV
Thursday, May 30, 2013
https://www.fightaging.org/archives/2013/05/an-interview-with-dmitry-itskov.php

Dmitry Itskov is the wealthy businessman who drives the 2045 Initiative, an advocacy and development program aimed at producing artificial replacements for the human body and eventually brain: a life extension plan that involves discarding as much of our biology as rapidly as possible. This is a stark contrast with other initiatives that aim to remove aging as a cause of death and disability by better maintaining our biology. The Global Futures 2045 conference is taking place in New York a few weeks, hence more media notice has been given to the project of late.

In this interview with Itskov you can see there is a lot of religious aspiration mixed in with the technological goals, which is both interesting from a cultural perspective and somewhat disquieting. Though perhaps the latter reaction is just parochial unfamiliarity at work - religion in public isn't something you typically see all that much of in the futurist and longevity science communities of the English-language world:

Basically, if you're asking me about what brought me to the project - to the idea - I would say it was kind of an evolution of my personal world view. You know, I had been successful in business, but I understood that I wasn't happy with just getting and spending money. It was just an epiphany when I realized that I wanted just to be of service to humanity - to create a project which will be really useful that could probably change the world. And I can further explain why I want it to be changed. I have always been in the technology business. I've always been connected to technology and I've been interested in life extension technology, but finally it was my personal spiritual quest and the desire to understand the real meaning of life and my place in this universe and that led me to the spiritual side of the project and I started meeting spiritual masters and talking to them - trying to ask them questions about the soul, about the nature of a human being. And from those meetings came the idea to mix science and technology and to establish a kind of public project which could raise all those questions which are so important to humanity now-a-days; the period when we are facing these numerous crises. In parallel with talking to spiritual masters, I started my consultations with scientists and that was how we created the broad map, which you can find on our website - the broad map of the Avatar Project.

So, the global goal is to create and realize a new strategy for the development of humanity which could meet global civilization changes and finally lead us to the kind of new world which will be based on five main principles, as I say. Those principles are high spiritually, high culture, high ethics, high science and high technologies. And the core of the idea is basically the assumption that now we need two revolutions. Two revolutions which actually plays in two parts: the first one is a spiritual one that could change the world view of people and the values which could set new goals and second is a technological revolution which could significantly accelerate the progress of the technology which would unite people and probably establish a new mega-project which could make the scientists in the future new super stars in our society.

LESS CANCER IN LONG-LIVED FAMILIES
Wednesday, May 29, 2013
https://www.fightaging.org/archives/2013/05/less-cancer-in-long-lived-families.php

Longevity is inherited to some degree, with the evidence suggesting that the contribution of your genes grows in importance in old age. Prior to that point, your lifestyle choices are far more significant to long-term health. Nonetheless, some genetic lineages are superior to others when it comes to tilting the odds in favor of a longer life. One of the objectives for longevity science is to make these differences irrelevant, swamping them in the benefits to health and longevity created by therapies capable of rejuvenation. For example, why would anyone care about inherited cancer risk if clinics could reliably cure or prevent all cancer? No-one cares about the genetic risks associated with influenza or smallpox, and that is exactly because these are controlled, cured conditions.

[Researchers] analysed data from a series of interviews conducted with 9,764 people taking part in the Health and Retirement Study. The participants were based in America, and were followed up over 18 years, from 1992 to 2010. [The scientists] discovered that people who had a long-lived mother or father were 24% less likely to get cancer.

The scientists compared the children of long-lived parents to children whose parents survived to average ages for their generation. The scientists classified long-lived mothers as those who survived past 91 years old, and compared them to those who reached average age spans of 77 to 91. Long-lived fathers lived past 87 years old, compared with the average of 65 to 87 years. The scientists studied 938 new cases of cancer that developed during the 18 year follow-up period.

They found that overall mortality rates dropped by up to 19 per cent for each decade that at least one of the parents lived past the age of 65. For those whose mothers lived beyond 85, mortality rates were 40 per cent lower. The figure was a little lower (14 per cent) for fathers, possibly because of adverse lifestyle factors such as smoking, which may have been more common in the fathers.

"Previous studies have shown that the children of centenarians tend to live longer with less heart disease, but this is the first robust evidence that the children of longer-lived parents are also less likely to get cancer. We also found that they are less prone to diabetes or suffering a stroke. These protective effects are passed on from parents who live beyond 65 - far younger than shown in previous studies, which have looked at those over the age of 80. Obviously children of older parents are not immune to contracting cancer or any other diseases of ageing, but our evidence shows that rates are lower. We also found that this inherited resistance to age-related diseases gets stronger the older their parents lived."

"Interestingly from a nature versus nurture perspective, we found no evidence that these health advantages are passed on from parents-in-law. Despite being likely to share the same environment and lifestyle in their married lives, spouses had no health benefit from their parents-in-law reaching a ripe old age. If the findings resulted from cultural or lifestyle factors, you might expect these effects to extend to husbands and wives in at least some cases, but there was no impact whatsoever."

FAT TISSUE DENSITY PREDICTS MORTALITY
Wednesday, May 29, 2013
https://www.fightaging.org/archives/2013/05/fat-tissue-density-predicts-mortality.php

Chronic inflammation appears to be a primary mechanism that links excess adipose tissue, fat in other words, with an increased risk of age-related medical conditions and early death. Become fat and you suffer far more inflammation than your thin peers, and that has a significant impact on your health over the years, even for comparatively modest gains in weight.

Here researchers demonstrate an association between increased mortality and a specific characteristic of fat tissue that doesn't appear to involve inflammation, however - so there must be other ways in which fat tissue sabotages your health and life expectancy:

Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics.

Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio [for] the densest quintile (Q5) versus least dense (Q1) for VAT density [was] 1.95 (Health ABC) and 1.88 (AGES-Reykjavik) and for SAT density, 1.76 (Health ABC) and 1.56 (AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52, whereas SAT density was associated with mortality in both Health ABC, 1.58, and AGES-Reykjavik, 1.43. Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs.

[We conclude that] VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.

ALZHEIMER'S DRUG CANDIDATE PROVIDES BENEFITS IN MICE WITHOUT CLEARING AMYLOID PLAQUES
Tuesday, May 28, 2013
https://www.fightaging.org/archives/2013/05/alzheimers-drug-candidate-provides-benefits-in-mice-without-clearing-amyloid-plaques.php

The cancer drug bexarotene has been shown to have potential as a treatment for Alzheimer's disease, at least in mice, but the latest research results show that it isn't working the way that researchers think it should. Incidentally, this sort of repurposing of an existing drug is a direct consequence of regulatory costs: it is so enormously expensive to go through the already excessive and expanding safety trials required by the US Food and Drug Administration for any new drug that companies prefer to eke out marginal benefits from existing drugs rather than work on building something new and better. This is one of the many ways in which the present state of medical regulation makes medicine worse.

[Researchers] reviewed previously published findings on the drug bexarotene, approved by the U.S. Food and Drug Administration for use in cutaneous T cell lymphoma. [They] were able to verify that the drug does significantly improve cognitive deficits in mice expressing gene mutations linked to human Alzheimer's disease, but could not confirm the effect on amyloid plaques.

[A] study was published last year stating that bexarotene improved memory and rapidly cleared amyloid plaques from the brains of Alzheimer's model mice expressing mouse Apolipoprotein E (APOE). Amyloid plaques consist of toxic protein fragments called amyloid beta that seem to damage neurons in the brain and are believed to cause the associated memory deficits of Alzheimer's disease and, eventually, death. Bexarotene is a compound chemically related to vitamin A that activates Retinoic X Receptors (RXR) found everywhere in the body, including neurons and other brain cells. Once activated, the receptors bind to DNA and regulate the expression of genes that control a variety of biological processes. Increased levels of APOE are one consequence of RXR activation by bexarotene.

"We were already set up to repeat the [study] to see if we could independently arrive at the same findings. While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains." [Researchers] postulate that the drug works through a different biological process, perhaps by reducing soluble oligomers which, like the plaques, are composed of the toxic amyloid beta protein fragments. However, the oligomers are composed of smaller amounts of amyloid beta and, unlike the plaques, are still able to "move."

"We did find a significant decrease in soluble oligomers. It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer's disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism."

LOOKING AT THE COMMERCIAL DEVELOPMENT OF RAPAMYCIN
Tuesday, May 28, 2013
https://www.fightaging.org/archives/2013/05/looking-at-the-commercial-development-of-rapamycin.php

The standard script is being followed for drug development based on rapamycin, by the look of things. Rapamycin reliably extends life in mice, which is more than can be said for the last set of overhyped alleged longevity-enhancing drugs, but it's still not worth getting excited about this sort of thing. The most likely end result is a rapamycin-like drug that lacks the worst side-effects, is of marginal benefit to humans, and which is only legally available as a palliative treatment for people suffering late-stage age-related disease - the regulatory environment in the US blocks all other options. Pharmacology to slow aging is simply not a viable path to greatly extended healthy life, and is of very limited use for old people.

A new study by Dr. Yiqiang Zhang and colleagues of the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio, has found that mice fed the drug rapamycin as part of their diet starting when they were 19 months old (roughly equivalent to 60 human years of age) had lifespan increases more modest than in some previous studies. Compared to untreated mice, the lifespan of the treated rodents increased by an average of about 3 percent, or 7 percent for mice who had lived to older age already.

The ability of rapamycin-related drugs to potentially slow the aging process as suggested in the animal experiments at The University of Texas Health Science Center San Antonio like the ones cited above, and others, led to establishment of a new biotech company, Rapamycin Holdings Inc., which is licensing exclusive rights to intellectual property central to several aspects of the rapamycin-related drugs, and which hopes to exploit new commercial possibilities for rapamycin. The company has announced that since 2010 it has been working to advance commercialization of products stemming from the patent pending technology developed by the Health Science Center researchers, and that more clinical trials will yield the next preclinical results by mid-year 2013, and advance Phase 1 trials shortly thereafter.

Rapamycin Holdings will be looking to raise an additional $6 million as it approaches the point of taking its first drug product to Phase 1 clinical trials. On December 7, 2012, Rapamycin Holdings Chief Executive Officer George Fillis announced that the company has acquired those exclusive rights from the UT Health Science Center and its collaborator, Southwest Research Institute. Rapamycin Holdings signed the license agreement with STTM, a multi-institution University of Texas technology-management office operated by the Health Science Center.

HEALTHSPAN CAMPAIGN
Monday, May 27, 2013
https://www.fightaging.org/archives/2013/05/healthspan-campaign.php

Here is another of the signs that the more conservative advocates for aging research are slowly moving towards a better position on human longevity. This is a new campaign that's somewhat like the Longevity Dividend, but a touch more ambitious in its tone. If you look at the proposed research agenda, you'll see that it's clearly not the rejuvenation biotechnology of SENS, as the declared aim is still only to slow aging, but it's a step in the right direction. A rising tide floats all boats, and the more that the mainstream of the research community agrees that something can and should be done about aging, the easier it becomes to gain support and funding for rejuvenation research:

Scientists who study aging now generally agree that it is malleable and capable of being slowed. Rapid progress in recent years toward understanding and making use of this malleability has paved the way for breakthroughs and interventions that will increase human health in later life by opposing the primary risk factor for virtually every disease we face as we grow older - aging itself. Better understanding of this "common denominator" of disease could usher in a new era of preventive medicine, enabling interventions that stave off everything from dementia to cancer to osteoporosis. Poised as we are for an unprecedented aging of our population and staggering increases in chronic age-related diseases and disabilities, even modest extensions of healthy lifespan could produce outsized returns of extended productivity, reduced caregiver burdens, lessened Medicare spending, and more effective healthcare in future years. The field of aging research is poised to make transformational gains in the near future. Few, if any, areas for investing research dollars offer greater potential returns for public health.

The payoffs from such focused attention and investment would be large and lasting. Therapies that delay aging would lessen our healthcare system's dependence on the relatively inefficient strategy of trying to redress diseases of aging one at a time, often after it is too late for meaningful benefit. They would also address the fact that while advances in lowering mortality from heart attack and stroke have dramatically increased life expectancy, they have left us vulnerable to other age-related diseases and disorders that develop in parallel, such as Alzheimer's disease, diabetes, and frailty. Properly focused and funded research could benefit millions of people by adding active, healthy, and productive years to life. Furthermore, the research will provide insights into the causes of and strategies for reducing the periods of disability that generally occur at the end of life. As University of Michigan gerontologist Richard Miller aptly puts it, "The goal isn't to prolong the survival of someone who is old and sick, but to postpone the period of being old and sick. Not to produce a lot more standard-issue 100-year-olds, but to produce a brand new kind of 100-year-old person."

STEPHEN CAVE DOESN'T GET IT
Monday, May 27, 2013
https://www.fightaging.org/archives/2013/05/stephen-cave-doesnt-get-it.php

Stephen Cave is the author of an interesting book on the relationship between the desire for immortality and the rise of civilization. In this short op-ed, however, his argument against the plausibility of radical life extension through progress in medical technology is a bad one, amounting essentially to "it hasn't happened yet, so it won't happen."

This is the hallmark of someone who doesn't have a good appreciation of the present state of scientific knowledge. Firstly, these are the opening years in a revolutionary leap in the capabilities of biotechnology and medicine: the speed of progress is far more rapid now than it has ever been. Secondly the SENS research program is a plausible, detailed path to halt and reverse degenerative aging, and could be completed in a couple of decades given sufficient funding. The logical outcome of working SENS therapies is that in the future people will live for thousands of years - and the timeline for development means that some of those people are alive today.

But there are plenty of folk who for various reasons don't want to hear any of that, and would rather just reject it all out of hand instead of taking a serious look at the evidence:

There is a dangerous idea gaining ground in our culture. It spreads with every headline that promises a cure for cancer or celebrates the discovery of a "gene for longevity". The idea is that science and technology can make us live forever. [You] will be familiar with the prophets of this movement: men such [as] Ray Kurzweil, who promises immortality by mid-century, or Aubrey de Grey, who says we will soon be living for 1,000 years. They claim that the progress we have seen in life expectancy in past centuries can be extended, even accelerated, until ageing, disease and death are defeated for good. One problem: it's not going to happen.

The ancient Egyptians thought they had cracked it 4,000 years ago. Two millennia later, China's First Emperor was convinced an elixir was within his grasp. Since then, sages and scientists have believed they could develop a potion that would turn back the clock. You may have heard about Harvard medical professor Charles-Édouard Brown-Séquard's theory that injecting extract of dog testicles would grant eternal youth; or the double Nobel Prize-winning Linus Pauling's campaign for vitamin C as the panacea for all our ills. All these believers have had one thing in common: they are now pushing up daisies.

Believers argue that the precedent of the past is not a good guide to the future - progress, after all, has never been more rapid. But the reality is that as our population ages, we are beginning to see the full extent of the toll time takes on us. One demographer has estimated that curing all cancers, heart disease and stroke - currently the three biggest killers in developed countries - would only push up life expectancy by 15 years as our body is crumbling anyway. There are many other Malthusian monsters waiting to finish us, from our own tendency to over-indulge in sugar and salt to our microbial enemies, who evolve as rapidly as we do. Surviving is not something that can be done by drinking a magic elixir: it must be done every minute of every day. And in the end probability will always be against us.

Present day medicine does nothing to change the root causes of age-related conditions. Patching over the damage of stroke does nothing to stop the next stroke, and successfully pushing a cancer into remission does nothing to address the DNA damage that progressively raises the odds of the next cancer occurring. The only way to live much longer than we do now is to repair the cellular and molecular damage that causes these conditions to exist, and also causes people to be old. This is a new approach to medical therapies for a new age of biotechnology. People like Cave have seen radical advances in medicine in their lifetimes - why are they so resistant to the idea that radical advances continue to take place?