FIGHT AGING! NEWSLETTER
February 20th 2012
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!
- SENS5 Video: Questions of Resource Allocation
- Eight Years of Fight Aging!
- A Few Items of Tissue Engineering News
- The Aging of Stem Cells
- On End of Life Timing for Cryonics
- Latest Headlines from Fight Aging!
SENS5 VIDEO: QUESTIONS OF RESOURCE ALLOCATION
Resources in research and medical development seems to be the unifying topic here at Fight Aging! for the past week or so. It is interesting to these accidental thematic collections of content come and go in passing, all without any deliberate intent; a reminder that we take small samples from a much broader, many-threaded conversation of millions of people, one that spans all media and has its tides and fashions at every timescale. So continuing the theme, here is a newly processed and posted video from the SENS5 conference:
EIGHT YEARS OF FIGHT AGING!
"The end of last month marked the close of the eighth year of Fight Aging!, and here we are in year nine of this bullheaded endeavor - the idea that the good can eventually drive out the bad in the online world of information on aging, longevity, and what best to do about the degenerations that await us all. Optimism shines eternal, I know, but as the science of human rejuvenation becomes ever closer to reality, the shysters and the marketeers of the 'anti-aging' industry must eventually go the way of the real snake oil salesmen of old, travelling cart and all. Along with them must go the apologists for aging, the people who would force death upon everyone, and the other malignant naysayers.
"Eight years was more than long enough for me to traverse that interesting section of life during which one first starts to notice the signs of decay - the things that don't work quite so well anymore, the initial small signs of what will be a lot worse later on. It makes it a good deal harder to avoid dwelling upon just how lousy the human condition is, all things considered. But that's all relative: I can tell you that the human condition is a raw deal because I can look ahead and see just how much of an improvement is possible through well-envisaged future technologies - not that there's anything special about being able to do that, but in this era we can be a lot more specific than our visionary ancestors. We can explain in some detail how we will defeat all disease, eliminate suffering, and of course remove aging as a threat to life and health. No serious, knowledgeable thinker can argue against these goals as possible and plausible, given our present understanding of physics and biology. We are machinery, our malfunctions are only a matter of atoms out of place, and precision control of atoms will be the basis for all of our technologies sooner or later. The world is our oyster in the realm of what is possible, but as always the question is how soon that future will arrive."
A FEW ITEMS OF TISSUE ENGINEERING NEWS
Tissue printing startup Organovo, which the Methuselah Foundation invested in some years back, has received a new round of funding. You'll find that and a couple of other recent items of interest from the tissue engineering field in the following Fight Aging! post:
"Organovo closed a private placement consisting of approximately 6.5 million units of its securities to qualified accredited investors, for total gross proceeds of $6.5 million. 'Organovo's advanced bioprinting platform can replicate essential biology for research, drug discovery and development and, eventually, for therapeutic applications,' stated Keith Murphy, chief executive officer of Organovo. 'We have found success in achieving early revenue through strategic collaborations, and this funding will allow us to extend the reach and uses of 3D bioprinting through growth and innovation in the coming years.'"
THE AGING OF STEM CELLS
Another in the series of posters from the Science for Life Extension Foundation has been translated from the original Russian. This one provides an overview of what is known of the mechanisms and details of aging stem cell populations and their impact on the body:
ON END OF LIFE TIMING FOR CRYONICS
Cryonics is the low temperature storage of the body after death, to preserve the fine structure of the brain to wait on future technologies that can repair cellular damage and restore these patients to active life. It's far from a sure thing, but it beats the alternative for the many in the community who won't live long enough to benefit from biotechnologies of rejuvenation. One of the hurdles that makes the organization of your own cryopreservation more expensive and uncertain than it has to be is that US law, where most cryonics providers are based, makes end of life determination largely illegal:
"One of the biggest challenges inherent in organizing your own cryopreservation in the US is that all of the best, most comfortable, and most optimal ways of timing the end of your life are illegal - not just for you, but for everyone who would be involved in helping you. This makes the act of cryopreservation vastly more expensive and prone to delays that will cause extensive damage to the fine structure of the brain, and all of this stems from the interference of state employees, enforcing laws made by other state employees who are both unaccountable and uncaring. Try to do the morally right thing and end up in jail. Thus teams must be on standby for weeks or months for any given patient who is approaching the end of their life, the patient must suffer through to the bitter end, and the time from notice of death to cooled vitrification of the body is inevitably much longer than it might otherwise be.
"This is why the right to self-determination in end of life choices, and the right to contract to help people enact those choices by providing goods and services, is so important for the cryonics community. But it should be important for everyone interested in enhanced human longevity: a government whose employees grant themselves the right to decide the timing of your death is a government that can also reach out to make it very hard to extend your life even if the means are available. And in fact, there is a lot of that already going on in the fact that therapies for aging cannot be approved for use in the US under the present system of regulation. That fact already goes a long way towards suppressing research and development towards that end goal. At root, this all comes back to self-ownership and self-determination: is it your life and your body? From modern government employees, the answer is largely 'no.'"
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!
INFLAMMATION AND THE STIFFNESS OF BLOOD VESSELS
Friday, February 17, 2012
One of the ways in which major blood vessels decline in function with aging is that they lose their elasticity. The state of chronic inflammation that grows with aging contributes to this, as noted in this open access paper (in PDF format). This is probably connected to the fact that exercise helps improve the elasticity of arteries, given that exercise is shown to impact levels of inflammation: "Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFβ precursors to produce active TGFβ, which then results in increased arterial fibrosis. ... There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-α therapy. ... Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments."
2ND INTERNATIONAL CONFERENCE ON AGING AND LONGEVITY
Friday, February 17, 2012
From Maria Konovalenko: "I am proud to announce that Science for Life Extension Foundation is one of the organizers of the 2nd international Genetics of Aging and Longevity conference. It is going to be an amazing and actually unprecedented conference focused on genetic mechanisms of aging and longevity. Check out the list of our invited speakers. I can't wait to hear the prominent researchers sharing their experience in making model animals live longer. By the way, we are proud to have all the longevity-record braking researchers, who extended the lifespan of yeast, nematodes, fruit flies and mice. You can't miss this meeting. I encourage you to go ahead and register. It's the end of April, beautiful spring in Moscow. For those who have never been here before, here's your chance to kill two birds with one stone - learn a lot about aging and discover one of the most beautiful and dynamic cities in the world."
SIMPLE MEASURES OF ROBUSTNESS PREDICT FUTURE HEALTH
Thursday, February 16, 2012
I would take this as an indicator that simple, ongoing maintenance of fitness and avoidance of a sedentary lifestyle pays off: "Simple tests such as walking speed and hand grip strength may help doctors determine how likely it is a middle-aged person will develop dementia or stroke. ... More than 2,400 men and women with an average age of 62 underwent tests for walking speed, hand grip strength and cognitive function. Brain scans were also performed. During the follow-up period of up to 11 years, 34 people developed dementia and 70 people had a stroke. The study found people with a slower walking speed in middle age were one-and-a-half times more likely to develop dementia compared to people with faster walking speed. Stronger hand grip strength was associated with a 42 percent lower risk of stroke or transient ischemic attack (TIA) in people over age 65 compared to those with weaker hand grip strength. This was not the case, however, for people in the study under age 65. ... Researchers also found that slower walking speed was associated with lower total cerebral brain volume and poorer performance on memory, language and decision-making tests. Stronger hand grip strength was associated with larger total cerebral brain volume as well as better performance on cognitive tests asking people to identify similarities among objects." We might theorize that this is related to exercise and blood flow in the brain, and related effects on the heath of blood vessels in the brain.
SHORTER TELOMERES CORRELATE WITH A HIGHER RISK OF HEART ATTACK AND EARLY DEATH
Thursday, February 16, 2012
Average telomere length in at least some tissues makes a good marker for general health, but the progressive shortening of telomeres may or may not be a root cause of aging. Telomere length results from a dynamic system of lengthening and shortening processes, which seems more likely to be a reflection of underlying function and dysfunction: "In an ongoing study of almost 20,000 Danes, a team of researchers [have] isolated each individual's DNA to analyse their specific telomere length - a measurement of cellular aging. ... The risk of heart attack or early death is present whether your telomeres are shortened due to lifestyle or due to high age ... The recent Copenhagen General Population Study involved almost 20,000 people, some of which were followed during almost 19 years, and the conclusion was clear: If the telomere length was short, the risk of heart attack and early death was increased by 50 and 25 per cent, respectively. ... That smoking and obesity increases the risk of heart disease has been known for a while. We have now shown, as has been speculated, that the increased risk is directly related to the shortening of the protective telomeres - so you can say that smoking and obesity ages the body on a cellular level, just as surely as the passing of time. ... one in four Danes has telomeres with such short length that not only will they statistically die before their time, but their risk of heart attack is also increased by almost 50 per cent. Future studies will have to reveal the actual molecular mechanism by which the short telomere length causes heart attacks. Does one cause the other or is the telomere length and the coronary event both indicative of a third - yet unknown - mechanism?" I lean towards the latter hypothesis, that both risk of catastrophic failure in bodily systems and telomere length reflect levels of accumulated damage at the level of cells and macromolecules in the body.
TRACING THE PATHWAY BACK FOR RESVERATROL
Wednesday, February 15, 2012
Resveratrol in and of itself is likely not terribly interesting for work on longevity - and certainly not worthy of the hype surrounding it. The same probably goes for sirtuins in general. This, however, is still a good example of work on tracing back the pathways of action of a metabolic change agent: "Research has previously suggested that resveratrol acts through activation of the sirtuin (SIR) gene family. This gene pathway, though controversial, has been implicated in life extension across several species. It has been reported that SIR extends lifespan in much the same way as caloric restriction which itself in turn may activate SIR. It has remained unclear however if resevertrol directly activates SIR or if it acts on SIR indirectly via another intermediary biochemical pathway. The current study successfully answered that question. Using several cell biology techniques the authors were able to demonstrate that resveratrol actually functions to activate SIR indirectly. They showed that resveratrol is really a phosphodiesterase inhibitor (PDE4). They demonstrated that reducing PDE4 allows cyclic AMP (cAMP) levels in the cells to rise. cAMP then increases the activity of AMPK which next increases NAD+ which finally increases SIR. This elegant study then went on to prove that the same life extending benefits of resveratrol could be achieved in rats by administering them the PDE4 inhibitor rolipram. ... inhibiting PDE4 with rolipram reproduces all of the metabolic beneﬁts of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. "
INVESTING IN LONGEVITY SCIENCE
Wednesday, February 15, 2012
An excellent article from CNBC looks at some of the few figures in the investment community who support progress towards extended healthy lifespans: "what if 'getting old' wasn't really 'getting old?' What if aging - at least the physical deteriorations that accompany it - was something that could be prevented? It's a lofty idea, but it's one that a new breed of biotech start-ups, scientists, and prominent investors are beginning to tackle. Peter Thiel is one of those investors. ... Back in 2006, Thiel gave Cambridge anti-aging researcher Aubrey de Grey $3.5 million under the auspices of the Methusaleh Foundation, a non-profit headquartered in Springfield, Virgina, that awards scientists who are working on life-extension therapies. 'Probably the most extreme form of inequality is between people who are alive and people who are dead,' Thiel told The New Yorker. In 2010, Thiel and his partners at Founders Fund, a Bay Area venture capital firm, invested $500,000 in Halcyon Molecular, a biotech start-up whose 28-year-old founder has a 'dream to create a world free from cancer and aging.' To understand the fund's investment, you have to appreciate what Founders Fund is - or, more specifically, what it is not. 'These are not guys who care about an extra million dollars,' says Brian Singerman, a partner at Founders Fund along with Thiel. 'These are guys who wanted to do something amazing for the world.' Singerman, an early employee at Google, [came] to Founders Fund after having what he describes as an 'epic six hour epic dinner with Sean Parker.' Equal parts brilliant and idealistic, Singerman is adamant that aging is a problem that can be solved. The fund's portfolio has invested in about 14 health and biotech companies all interested in solving life's ultimate problem: death. ... We have a company that's charged with curing all viral disease, we have a company that's charged with curing several types of cancer. These are not things that are incremental approaches. It's all fine and good to have a drug that extends life by a certain amount of months or makes living with a disease easier. That's not what we're looking for. We are not looking for incremental change. We are looking for absolute cures in anything we do."
MORE EATING, MORE MEMORY LOSS
Tuesday, February 14, 2012
Another good reason to be practicing calorie restriction: "New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. ... We observed a dose-response pattern which simply means; the higher the amount of calories consumed each day, the higher the risk of MCI. ... The study involved 1,233 people between the ages of 70 and 89 and free of dementia residing in Olmsted County, Minn. Of those, 163 had MCI. Participants reported the amount of calories they ate or drank in a food questionnaire and were divided into three equal groups based on their daily caloric consumption. One-third of the participants consumed between 600 and 1,526 calories per day, one-third between 1,526 and 2,143 and one-third consumed between 2,143 and 6,000 calories per day. The odds of having MCI more than doubled for those in the highest calorie-consuming group compared to those in the lowest calorie-consuming group. The results were the same after adjusting for history of stroke, diabetes, amount of education, and other factors that can affect risk of memory loss. There was no significant difference in risk for the middle group."
TREATING HEART ATTACK DAMAGE WITH STEM CELLS
Tuesday, February 14, 2012
A recent trial shows benefits: "treating heart attack patients with an infusion of their own heart-derived cells helps damaged hearts re-grow healthy muscle. Patients who underwent the stem cell procedure demonstrated a significant reduction in the size of the scar left on the heart muscle by a heart attack. Patients also experienced a sizable increase in healthy heart muscle following the experimental stem cell treatments. One year after receiving the stem cell treatment, scar size was reduced from 24 percent to 12 percent of the heart in patients treated with cells (an average drop of about 50 percent). Patients in the control group, who did not receive stem cells, did not experience a reduction in their heart attack scars. ... While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle. This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests. ... In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack."
AN APPROACH TO SPURRING REGROWTH OF BLOOD VESSELS
Monday, February 13, 2012
Researchers are working on many different approaches to spur regrowth of blood vessels in the body. Here is one of them: "researchers have demonstrated a new and more effective method for regrowing blood vessels in the heart and limbs ... The treatment method [could] allow doctors to bypass surgery and instead repair damaged blood vessels simply by injecting a lipid-incased substance into a patient. Once inside the body, the substance stimulates cell growth and spurs the growth of new blood vessels from pre-existing ones. ... Others have tried using growth factors to stimulate vessel growth in clinical trials and have not been successful. We think that a major reason for this is that previous methods assumed that the diseased tissues retained the ability to respond to a growth stimulus. Our method basically delivers extra components that can restore growth factor responsiveness to the tissue of patients with long-standing clinical disease. ... The method combines a growth factor - a substance capable of stimulating cellular growth, proliferation and cellular differentiation, as well as healing wounds - known as fibroblast growth factor 2 (FGF-2) with a lipid-embedded receptor to enhance its activity. A challenge for scientists and engineers, however, has been getting FGF-2 to bind with cell receptors - the very molecules often found on the surface of the cell that receive chemical signals and direct activity in the cell from outside sources. To overcome this, [the new] method embeds the growth factors in synthetic lipid-based nanoparticles containing a coreceptor known as syndecan-4. The nanoparticles containing co-receptors that, when delivered with the growth factor, enable improved cell binding so that the growth factor can direct the targeted cell to divide, proliferate and form new cells for tissue regrowth. The incased substance was injected into rats with hindlimb ischemia and stimulated a complete recovery from the ischemia in just seven days."
BOOSTING REPAIR OF MYELIN SHEATHS IN THE BRAIN
Monday, February 13, 2012
Researches have been boosting stem cell populations via the method demonstrated here for more than five years, but here they're demonstrating a better and more refined outcome: "myelin [is] a material that forms a protective, insulating cape around the axons of our nerve cells so that they can send signals quickly and efficiently. But myelin, and the specialized cells called oligodendrocytes that make it, become damaged in demyelinating diseases like multiple sclerosis (MS), leaving neurons without their myelin sheaths. As a consequence, the affected neurons can no longer communicate correctly and are prone to damage. ... We've developed a gene therapy to stimulate production of new oligodendrocytes from stem and progenitor cells - both of which can become more specialized cell types - that are resident in the adult central nervous system. In other words, we're using the brain's own progenitor cells as a way to boost repair. ... The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models. ... What hadn't been done before our study was to use gene therapy in the brain to stimulate these cells to remyelinate. ... It was thought that you could use factors to stimulate the division and expansion of the progenitor population, and then add additional factors to direct those progenitors to turn into the mature myelin-forming cells. But in our mouse model, when we give our LIF therapy, it both stimulates the proliferation of the progenitor cells and allows them to differentiate into mature oligodendrocytes."