Science recently hosted a live chat event with researchers Aubrey de Grey and S. Jay Olshansky, public figures who have debated their views on longevity science a number of times over the last seven years or so. The logs and viewer comments from the event remain available for those interested in viewing the discussion, but note that it takes a little while for the widget containing them to load.

Live Chat: The Science of Antiaging

Jennifer Couzin-Frankel: And here's a question from Roy: Does the paper titled "Clearance of p16 positive senescent cells delays ageing-associate disorder" published in Nature January, 2011, prove the Strategies for Engineered Negligible Senescence (SENS's) validity, i.e. extend lifespan by remediating damage? If so, are their other examples of experimental validation of SENS in animal models?

Aubrey: Roy: that paper is a great proof of concept for one component of SENS, the benefits of removing "death-resistant" cells. The experiment didn't show life extension, but it wasn't expected to, because to do that you have to fix all the things that limit lifespan, not just one of them. Yes, there are various other examples, such as the elimination of amyloid in mouse models of Alzheimer's and the introduction of stem cells (or the stimulation of their division) in various tissues. We'll see more of this soon, that's for sure.

...

Jennifer Couzin-Frankel: An interesting question from Morten: Why do you want to live longer (as I understand it at least de Grey is after living longer)? What can't you accomplish in a life time?

Aubrey: Morten: this is the most insidious misunderstanding of the work that I and other biomedical gerontologists do. We are NOT working to extend life for the sake of extending life. We are working to postpone the ill-health of old age, which will probably have the side-effect of extending life, but it's no more than that, a side-effect. I personally have no idea how long I want to live, [any] more than I have an opinion on what time I want to go to the toilet next Sunday. In both cases I know I'm going to have better information nearer the time, so it's idiotic to even think about it. However, I can tell you that I have at least 1000 years of backlog already (books to read, films to se...) - don't you? If not, why not?

S. Jay Olshansky: Morton. The goal of research in this area in my view is not to extend life. The goal is to extend healthy life. If we live longer, I consider that a bonus. However, I would encourage you to be asking the same question of those now working to combat heart disease, cancer, and stroke, and those who experience these conditions. Why [do] we all want to live longer? I believe what we are talking about here are interventions that enable us to live our lives healthy for as long as possible.

...

Comment From Guest: Couldn't you guys be focusing on pain control, quality-of-life and ending poverty and depression in the elderly?

S. Jay Olshansky: [Think] about this for a moment. In 1900 life expectancy at birth was about 45. Now it's about 80 for women and 76 for men. We gained 30 years of life -- most healthy. Wasn't that worth it? It's hard to imagine the goal of extending healthy life as being harmful in any way -- it would enable people to remain working longer if they want, or retire healthier for a longer time period. Health also begets wealth for individuals and populations. Goodness -- why are we working so hard to combat heart disease and cancer then?

There's a lot more there to look through; you should certainly read the whole thing.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

From the Independent: "It is one of medicine's mysteries: what has caused Britain's plummeting rate of heart disease over the last decade? Deaths from heart attacks have halved since 2002 and no one is quite sure why. Similar changes have occurred in countries around the world but the death rate in England, especially, has fallen further and faster than almost anywhere. ... The researchers looked at 840,000 men and women in England who had suffered a total of 861,000 heart attacks between 2002 and 2010. Overall, the death rates fell by 50 per cent in men and 53 per cent in women. ... For the last 70 years we have been in the grip of a heart disease epidemic that began in the 1940s, rose to a peak in the 1970s and then began to fall. All Western countries were affected and all followed broadly the same pattern. ... researchers conclude that just under half the decline in heart attack death rates in England over the last decade is due to better hospital treatment; the rest is due to changes in lifestyle and the widespread use of pills to lower cholesterol and blood pressure." One might theorize that - at the high level - increased heart disease across the last seven decades is a consequence of the fat and sedentary lifestyles that tend to accompany increases in wealth across the board, while reductions are largely due to improvements in medical technology.

Link: http://www.independent.co.uk/life-style/health-and-families/health-news/the-curious-case-of-the-vanishing-killer-6294626.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Here is an open access PDF format mini-review on what is known of growth hormone and aging - that less of it is generally better: "A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22261798

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Here is an open access PDF format mini-review on what is known of growth hormone and aging - that less of it is generally better: "A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22261798

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The course of our future lives, our health and longevity, is swayed by a population of timid mice - but malicious mice, ever ready to use state force to punish and hold back anyone they see as being insufficiently timid. These are people who support the ball and chain of centralized regulation of medical research, people who fear all change, people who fear everything they don't understand, and people who rush to prevent anyone else from enjoying the freedom to undertake personal risk in the course of advancing progress. This describes the vocal mainstream of Western culture: risk-averse, ignorant, and enamored of control for its own sake: a dangerous combination for those who pull upon the strings of law and regulation.

As I have often remarked in the past, freedom is absolutely essential to progress in medicine: the freedom for researchers to attempt goals as they see fit; the freedom for anyone to fund the research and clinical development they desire; the freedom for people to take personal risks in the use of medical technology; the freedom for groups to create an unhampered marketplace in medicine, in which technologies are rapidly sifted for those with the greatest benefit. These are all simply parts of economic and personal liberty, something that is in extremely short supply in the medical industry.

So the mice stamp their little feet, and the impersonal engines of government - the unaccountable employees of bureaucratic bodies such as the FDA - move to prevent us all from undertaking rapid development in medicine, on penalty of jail. For our own good, supposedly.

If anti-aging drugs are possible, they will require dangerous - and ethically troubling - clinical trials. ... If anti-aging medicine is to become a reality, then the various theories about how to halt or reverse the aging process will require testing on human subjects. Carrying out such tests will place unprecedented pressure on the rules protecting human participants in clinical trials. I suspect, then, that human guinea pigs for anti-aging trials will come disproportionately from the poor and disempowered. ... The rich and powerful will be looking to do away with rules that they perceive as denying them millennial life spans.

Those would be the rules preventing terminal cancer patients from choosing to up and pay for their own personal trial of a promising therapy-in-development - forcing them to die without any recourse. The rules that make formal clinical trials so lengthy and expensive that many potential therapies are simply never developed or tried by humans, and those that are might be a decade in the slow regulatory grind from readiness to actual availability. The rules that raise the costs of medicine too high for those poor folk that the author seems to be concerned about. Regulation of medicine, which raises costs, disrupts the effective market mechanisms of progress, and prevents people from using potential therapies that are technologically feasible and ready to field-test, is a morally bankrupt affair.

But this is the culture we live in, sad to say: one in which vague and poorly articulated discomfort with potential future inequities are given more consideration than the ongoing massive toll of death and suffering that we should be working day and night, as fast as possible, to prevent. A toll of 100,000 lives every day, and the hundreds of millions who are crippled, diminished, and in pain. Instead we get institutions like the FDA, whose staff toil to prevent new medicine from ever seeing the light of day. The mice would close their eyes and drown the world in blood just to feel a little better in their own vague sense of disquiet: they are the very worst of humanity, not even willing to acknowledge the fearsome costs of their own timidity.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Here is another example of work on creating patient-specific cells to order, one of the necessary building block technologies needed for an industry that constructs organs and other larger masses of tissue in the body: researchers have "discovered a method of generating different types of vascular smooth muscle cells (SMCs) - the cells which make up the walls of blood vessels - using cells from patients' skin. ... Cardiovascular disease is the leading cause of death in the world. These deaths are mainly caused by the hardening and subsequent blockage of blood vessels due to the accumulation of fatty materials, a condition called atherosclerosis. As not all patients are suitable for conventional stenting or bypass treatment, an option in the future may be to grow new blood vessels to bypass their own blocked vessels. The [team] worked with embryonic stem cells and reprogrammed skin cells, collectively known as human pluripotent stem cells (hPSCs), which have the potential to form any cell type in the body. They discovered a method of creating all the major vascular smooth muscle cells in high purity using hPSCs which can also be easily scaled up for production of clinical-grade SMCs. This is the first time that such a system has been developed and will open the door for comparative studies on different subtypes of SMCs to be carried out, which are otherwise extremely difficult to obtain from patients."

Link: http://medicalxpress.com/news/2012-01-cambridge-team-smooth-muscle-cells.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The principle use of stem cells in the near future is actually research, not therapy - generating diseased cells to order will lower the cost of better understanding the mechanisms of disease and age-related conditions. For example: "scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease (AD), using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder. ... It's a first step. These aren't perfect models. They're proof of concept. But now we know how to make them. It requires extraordinary care and diligence, really rigorous quality controls to induce consistent behavior, but we can do it. ... We're dealing with the human brain. You can't just do a biopsy on living patients. Instead, researchers have had to work around, mimicking some aspects of the disease in non-neuronal human cells or using limited animal models. Neither approach is really satisfactory. ... With the in vitro Alzheimer's neurons, scientists can more deeply investigate how AD begins and chart the biochemical processes that eventually destroy brain cells associated with elemental cognitive functions like memory. Currently, AD research depends heavily upon studies of post-mortem tissues, long after the damage has been done. ... The differences between a healthy neuron and an Alzheimer's neuron are subtle. It basically comes down to low-level mischief accumulating over a very long time, with catastrophic results. ... The researchers have already produced some surprising findings. ... In this work, we show that one of the early changes in Alzheimer's neurons thought to be an initiating event in the course of the disease turns out not to be that significant."

Link: http://www.sciencedaily.com/releases/2012/01/120125131029.htm

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The principle use of stem cells in the near future is actually research, not therapy - generating diseased cells to order will lower the cost of better understanding the mechanisms of disease and age-related conditions. For example: "scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease (AD), using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder. ... It's a first step. These aren't perfect models. They're proof of concept. But now we know how to make them. It requires extraordinary care and diligence, really rigorous quality controls to induce consistent behavior, but we can do it. ... We're dealing with the human brain. You can't just do a biopsy on living patients. Instead, researchers have had to work around, mimicking some aspects of the disease in non-neuronal human cells or using limited animal models. Neither approach is really satisfactory. ... With the in vitro Alzheimer's neurons, scientists can more deeply investigate how AD begins and chart the biochemical processes that eventually destroy brain cells associated with elemental cognitive functions like memory. Currently, AD research depends heavily upon studies of post-mortem tissues, long after the damage has been done. ... The differences between a healthy neuron and an Alzheimer's neuron are subtle. It basically comes down to low-level mischief accumulating over a very long time, with catastrophic results. ... The researchers have already produced some surprising findings. ... In this work, we show that one of the early changes in Alzheimer's neurons thought to be an initiating event in the course of the disease turns out not to be that significant."

Link: http://www.sciencedaily.com/releases/2012/01/120125131029.htm

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

This year's Buck Symposium, an event hosted by the Buck Institute for Research on Aging, will be held on March 1st. The Institute is very much a part of the mainstream of biogerontology, wherein frank talk of extending human life span is rare, and the public relations tends to focus on age-related diseases and length of healthy life within the current human life span:

At the Buck Institute, world-class scientists work in a uniquely collaborative environment to understand how normal aging contributes to the development of conditions specifically associated with getting older such as Alzheimer's and Parkinson's disease, cancer, stroke, heart disease, diabetes, macular degeneration and glaucoma. Our interdisciplinary approach brings scientists from disparate fields together to develop diagnostic tests and treatments to prevent or delay these maladies.

Some of their work has application to more useful research programs, however, those that aim directly to extend human life and reverse aging - such as SENS. That said, the program for the event is attractive, and in the speakers list you'll see a few noted researchers who are in fact public supporters of SENS, such as Irina Conboy.

The 2012 Buck Symposium: Stem Cell Research and Aging provides a stage for key players in the rapidly developing areas of stem cell research and the basic biology of aging to share their research, findings and thoughts. Some of the world's most influential and respected investigators from diverse background, in fields such as development, diseases, stem cell biology and model systems will be sharing their ideas, sparking new dialog, new alliances and promising collaborations.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

From the New York Times: "A treatment for eye diseases that is derived from human embryonic stem cells might have improved the vision of two patients. The report, published online in the medical journal The Lancet, is the first to describe the effect on patients of a therapy involving human embryonic stem cells. ... The results [come] from the second clinical trial involving the stem cells, using a therapy developed by Advanced Cell Technology to treat macular degeneration, a leading cause of blindness. ... Both patients, who were legally blind, said in interviews that they had gains in eyesight that were meaningful for them. One said she could see colors better and was able to thread a needle and sew on a button for the first time in years. The other said she was able to navigate a shopping mall by herself. ... esearchers at Advanced Cell Technology turned embryonic stem cells into retinal pigment epithelial cells. Deterioration of these retinal cells can lead to damage to the macula, the central part of the retina, and to loss of the straight-ahead vision necessary to recognize faces, watch television or read. Some 50,000 of the cells were implanted last July under the retinas in one eye of each woman in operations that took about 30 minutes. ... Before the treatment, the woman with Stargardt's was able to see the motion of a hand being waved in front of her but could not read any letters on an eye chart. Twelve weeks after the treatment, she was able to read five of the biggest letters on the eye chart with the treated eye, corresponding to 20/800 vision, according to the paper."

Link: http://www.nytimes.com/2012/01/24/business/stem-cell-study-may-show-advance.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

An interview with a researcher: "Advances in the study of stem cells have fueled hopes that someday, via regenerative medicine, doctors could restore aging people's hearts, livers, brains and other organs and tissues to a more youthful state. A key to reaching this goal - to be able to provide stem cells that will differentiate into other types of cells a patient needs - appears to lie in understanding 'epigenetics,' which involves chemical marks stapled onto DNA and its surrounding protein husk by specialized enzyme complexes inside a cell's nucleus. These markings produce long-lasting changes in genes' activity levels within the cell - locking genes into an 'on' or 'off' position. Epigenetic processes enable cells to remain true to type (a neuron, for instance, never suddenly morphs into a fat cell) even though all our cells, regardless of type, share the same genetic code. But epigenetic processes also appear to play a critical role in reducing cells' vitality as they age. ... Aging seems to involve a gradual deterioration of function as cells and tissues are exposed to stresses either from outside the body, such as chemicals we ingest or irradiation from the sun, or from inside the body, such as free radicals, produced every moment when cells are making energy. These myriad insults can, among other things, alter a cell's epigenetic settings, resulting in changed patterns of gene activity that diminish the cell's overall ability to function. ... Although some aspects of cellular aging - DNA mutations, for instance - would be difficult to 'reset,' we and others have done experiments suggesting that many of the characteristics of old cells and tissues can indeed be reversed, restoring them to a more youthful state. Much of our work has focused on stem cells, and in particular on the changes that occur with age and that reduce stem cells' ability to maintain or repair tissues. Our findings fit nicely with the idea that some of the causes of aging are epigenetic in character, as opposed to actual damage to genes. Most importantly, our data suggest that cells and tissues can be rejuvenated without losing their specific characteristics - old muscle stem cells, when rejuvenated, remain muscle stem cells rather than become some more generic, undifferentiated cell."

Link: http://med.stanford.edu/ism/2012/january/5q-rando-0123.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Exercise extends healthy life in laboratory animals, but not maximum life span as is the case for calorie restriction. In longer lived species such as our own, that difference may be slight: present evidence suggests exercise and calorie restriction to have broadly similar - though very different in detail - effects on life expectancy. The end results are probably in the same ballpark, and quite possibly achieved through an overlapping set of mechanisms. That said, while exercise is certainly good for you, I've yet to see a study on exercise that reproduces similar eye-opening changes in underlying biomarkers of health to those found in human calorie restriction practitioners. Exercise is "merely" great for health, as opposed to amazingly superb for health.

So, obviously, the sensible thing to do is both exercise regularly and practice calorie restriction. Based on the weight of evidence, this is the 80/20 of what can be done today to optimize health for the long term in a basically healthy individual. The complement to this approach is doing your part to ensure that medical technology produces methods of rejuvenation in time to help you in later age when good health practices are no longer enough to stave off significant degeneration and risk of death.

There is a school of thought that places the processes of autophagy front and center when it comes to natural methods of adjusting metabolism for length of health and life. Autophagy is the process by which cells break down damaged components, the first step in recycling and replacement: fewer damaged components at any given time is a good thing, and so more autophagy should also be a good thing. You might recall a demonstration that autophagy is essential to the life span and health benefits of calorie restriction, for example.

I notice that scientists are suggesting that autophagy is similarly important to the health and life span benefits produced by regular exercise:

Dr Levine and her team were testing a theory that exercise works its magic, at least in part, by promoting autophagy. This process, whose name is derived from the Greek for "self-eating", is a mechanism by which surplus, worn-out or malformed proteins and other cellular components are broken up for scrap and recycled.

To carry out the test, Dr Levine turned to those stalwarts of medical research, genetically modified mice. Her first batch of rodents were tweaked so that their autophagosomes - structures that form around components which have been marked for recycling - glowed green. After these mice had spent half an hour on a treadmill, she found that the number of autophagosomes in their muscles had increased, and it went on increasing until they had been running for 80 minutes.

To find out what, if anything, this exercise-boosted autophagy was doing for mice, the team engineered a second strain that was unable to respond this way. Exercise, in other words, failed to stimulate their recycling mechanism. When this second group of modified mice were tested alongside ordinary ones, they showed less endurance and had less ability to take up sugar from their bloodstreams.

There were longer-term effects, too. In mice, as in people, regular exercise helps prevent diabetes. But when the team fed their second group of modified mice a diet designed to induce diabetes, they found that exercise gave no protection at all.

Autophagy is one of a number of potential mechanisms by which exercise improves long term health. You might look back at a post from the archives for more:

Physical inactivity is increasingly recognized as modifiable behavioral risk factor for cardiovascular diseases. A partial list of proposed mechanisms for exercise-induced cardioprotection include induction of heat shock proteins, increase in cardiac antioxidant capacity, expression of endoplasmic reticulum stress proteins, anatomical and physiological changes in the coronary arteries, changes in nitric oxide production, adaptational changes in cardiac mitochondria, increased autophagy, and improved function of sarcolemmal and/or mitochondrial ATP-sensitive potassium channels. It is currently unclear which of these protective mechanisms are essential for exercise-induced cardioprotection. ... A better understanding of the molecular basis of exercise-induced cardioprotection will help to develop better therapeutic strategies.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm