Fight Aging! Newsletter, October 10th 2011

October 10th 2011

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!



- Actuaries and Public Understanding of Longevity Science
- The Changing Understanding of Aging
- Commentary Divorced from Reality
- In Search of Epigenetic Predictors of Longevity
- The Financial Challenges of Cryonics
- Discussion
- Latest Headlines from Fight Aging!


The scientific and popular science publishing industries are not the only road by which public understanding and support of longevity science can increase:

"People who make decisions involving very large amounts of money are not necessarily right any more often than the rest of us, but they do put in a great deal more groundwork and research in the course of making these decisions. In the gargantuan life insurance and pensions marketplace, where the long-term success of multinational conglomerates rests on good predictions of life expectancy, that amounts to a lot of time spent thinking about the near future of human longevity and medical technology.

"I look on all this activity in two ways: firstly, it is a useful pathway for wider education on longevity science. The actuaries are aware of research and its implications long before the general public, and they are also hooked into business machinery that widely publishes their analysis and viewpoints. As a result, many people will be convinced about the prospects for engineered human longevity by the materials produced by the financial industry rather than those produced by patient advocates, scientists, and the medical industry.

"Secondly, the work and publications of actuaries are a barometer for how compelling and widespread the arguments have become for significantly extending healthy human life through biotechnology. In this, I tend to pay attention to the pace at which their estimates are changing rather than the estimates themselves - it is my opinion that great financial upheaval lies ahead as sudden, large, and uncertain gains in life expectancy for older people are unlocked by advances in biotechnology. Present estimates are rather tied to the slow model of incidental life extension rather than the far more uncertain timeframe for the arrival of ways to achieve deliberate slowing and reversal of aging."


A series of open access review papers aimed at an audience unfamiliar with modern aging research are linked in the following Fight Aging! post:

"I stumbled upon a series of open access review papers today, entitled "The Changing Understanding of Aging," written by a veterinarian for an audience of practitioners largely unfamiliar with the history and present state of aging research. As a consequence it's very readable for the layperson, and it really doesn't matter that the papers are as much focused on the animal kingdom as on human research: at the high level much of what is the case for the mammals we keep as pets is also the case for humans - the same theories apply. Only the details of our biochemistries are different, which does lead to greatly differing life spans and rates of aging, but all proceeding according to much the same fundamental mechanisms."


Why is it that the prospect of rejuvenation biotechnology causes people to spout nonsense about class warfare, death before inequality, and the like, when little of that happens for radical progress in cancer therapies, or regenerative medicine to build new organs?

"there is something about the idea of greatly extending human life through medical technology that sends otherwise sane people off the deep end. Mention the topic and you'll hear screeds on class warfare, relinquishment of progress in medicine, death before inequality, and visions of immortal tyrants lording it over mortal serfs. Nonsense, the lot of it, all utterly divorced from the history that shows us time and again exactly how change, even radical change, progresses in a technological society - but people say this stuff anyway. ... People react to the prospect of rejuvenation biotechnology in ways that are completely different from their reactions to, say, the highly effective next generation of cancer therapies. You don't hear people declaring that late stage treatments for cancer will split the world into warring factions of haves and have nots, or that all development must be halted until it can be offered to everyone. If you walk through all the varied nonsense spouted on the topic of society and radical life extension, and replace rejuvenation with stem cell heart therapies, or cures for cancer, or organs such as blood vessels grown to order - then you might start to see just how nutty it sounds. Medical technologies just as revolutionary have emerged in the past, and will continue to do so without being hoarded, restricted to the rich, tearing the world asunder, turning brother against brother, and causing cats to lie with dogs."


The study of epigenetics is growing in breadth, which means that researchers are starting to search for correlations between epigenetic changes and longevity:

"The DNA in every one of our cells is better thought of as a whirling, dynamic machine rather than a static blueprint. It is in motion, a blur, a thousand thousand feedback loops involving the production of proteins that selectively alter the process of producing proteins. The amount of any one specific protein in a given cell produced from its DNA blueprint rises and falls dynamically, in response to environmental conditions, time of day, status of the cell's internal machinery, and a million other variations tuned by evolution. The epigenome is this dynamic partner to the static genome, a catalog of how genes become tagged and the changes that result from those tags. Epigenetics is the study of how DNA interacts with the machinery of protein construction to selectively modify the output in response to circumstances - and what that then means for cells, organs, and the operation of the body as a whole.

"Just as there are genetic variations that subtly contribute to human longevity, we should expect there to be equally subtle epigenetic variations - though more complex, and harder to uncover. Research here contributes to the grand debate over the degree to which aging is programmed: is the epigenetic contribution to aging a matter of growing disarray in the processes of tagging and correcting levels of protein production, arising due to damage, or are there signs of programmed changes in levels of protein production that cause damage and dysfunction?

"The educated guess at this point is that the way in which natural, unmodified life span emerges depends a little on the DNA blueprint, a lot on the environment, but just as much on chains of chaotic happenstance in the enormously complex operations of metabolism. We might consider that last line item a form of stochastic accumulation of molecular damage to cells: even with all other things being equal, individuals will age at somewhat different rates because initially small, localized differences in biological damage snowball over time into widely diverging system-wide outcomes."


Industries that offer products and services that span decades face challenges relating to the devaluation of currency that are generally not well understood by most businesses:

"Long-standing businesses must index everything they do to the changing - almost always falling - value of their regional currency, but very few smaller businesses do this in any sort of a deterministic way. Your average talented and determined fellow willing to start a company knows a lot about the business itself, but generally isn't very knowledgeable regarding currencies, inflation, finance, and so forth. That sort of expertise doesn't emerge in a company as a matter of course until it becomes much larger. So smaller businesses deal with the falling value of money by raising their prices as best they can on an ad hoc basis, but this is ever a challenge for products that involve very long memberships. Trying to raise rates on existing customers is, frankly, one of the hardest things a business can do. But raise rates they must, as modern paper currencies have long been set on a relentless spiral of devaluation.

"This happens because politicians and government bureaucrats can use the strategic devaluation of their national fiat currency as a way to generate significantly more revenue for a given level of public upheaval than can be achieved through direct taxation - so of course they tend to do exactly that. This is why inflation exists, and is arguably why fiat currencies continue to enjoy such wide, legally-enforced use. So fiat currencies are somewhat systematically, somewhat opportunistically devalued over time in ways that result in a transfer of wealth from the public at large and into the control of politicians, bureaucrats, and their close supporters.

"The cryonics industry is presently running into [this] issue]. It offers products that are commonly paid for over decades, or where decades might elapse between the ink drying on a contract and the actual provision of service. The industry is decades old, but never grew to the point at which experience in managing the consequences of currency devaluation and other long-term strategic issues would naturally emerge amongst the major players in a field. At Alcor, this manifests as a growing underfunding issue, and to the credit of the present management they are openly publishing their current thinking on the matter."

If you have an interest in cryonics, I strongly suggest you read the Alcor document; it makes for interesting reading. I think an organization willing to put out a document that talks through their issues in this way is an organization with the right mindset to come to a solution. Openness is a virtue in this modern world.


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!



Friday, October 7, 2011
It is the common wisdom that retirement from active work speeds the process of decline - and there are all sorts of reasonable explanations as to why this might be the case, but insofar as actual supporting evidence goes you're not going to find much of a consensus. That said, here is an unusual paper amongst those in search of a correlation between retirement and a shorter remaining life span: "Mortality hazard and length of time until death are widely used as health outcome measures and are themselves of fundamental demographic interest. Considerable research has asked whether labor force retirement reduces subsequent health and its mortality measures. Previous studies have reported positive, negative, and null effects of retirement on subsequent longevity and mortality hazard, but inconsistent findings are difficult to resolve because (1) nearly all data confound retirement with unemployment of older workers, and often, (2) endogeneity bias is rarely addressed analytically. To avoid these problems, albeit at loss of generalizability to the entire labor force, I examine data from an exceptional subgroup that is of interest in its own right: U.S. Supreme Court justices of 1801-2006. Using discrete-time event history methods, I estimate retirement effects on mortality hazard and years-left-alive. ... Estimates by all these methods are consistent with the hypothesis that, on average, retirement decreases health, as indicated by elevated mortality hazard and diminished years-left-alive. These findings may apply to other occupational groups characterized by high levels of work autonomy, job satisfaction, and financial security."

Friday, October 7, 2011
Extreme Longevity notes an Italian study: "Sardinia [is] especially rich in male centenarians. The present study was undertaken to quantify and determine which particular lifestyle and nutritional variables endemic to Sardinia males accounted for their extreme longevity. The authors point out that no genetic differences have been found between Sardinian males and less long-lived males found elsewhere in Italy so they reasoned lifestyle choices were more likely causative of their longevity than genetic factors. The researchers specifically compared the frequency of several dietary choices and lifestyle factors between men of Sardinia and Italian men not from Sardinia. It was particularly surprising that diet alone didn't account for the differences. The frequency of meat, cheese, wine, grain and nut consumption was identical in the two groups. Total daily caloric intake was slightly but insignificantly lower in the Sardinian men. The most significant difference found was in the distance to work and average slope of the terrain between the men of Sardinia and those from other regions. The researchers conclude it is likely the large amount of daily physical exercise required to walk long distances up steep mountain climbs that has led to the increased longevity of Sardinian males. They point out the effect of physical exercise on extending longevity is becoming widely recognized, appearing at the conclusion of many scientific articles."

Thursday, October 6, 2011
Researchers continue to explore what stem cells might be able to achieve for the regeneration of serious injuries: "adult human mesenchymal stem cells may have an important role in the treatment and repair of spinal cord injuries. Mesenchymal stem cells (MSCs) are found mainly in the bone marrow and are the focus of many clinical trials that investigate potential methods of neurological repair and other regenerative applications. ...Although mesenchymal stem cells are widely known to be used in replacing damaged tissue, these stem cells may also recruit endogenous cells (those made within the body) to help accelerate the repair process. ... For the first time, [researchers] examined the use of human MSCs to prompt repair of spinal cord injuries in transgenic (genetically engineered or altered) zebrafish embryos. Zebrafish are especially valuable to researchers due to invertebrate characteristics that are similar to those of humans, the transparency of their bodies and their ability to initiate regeneration of damaged tissue. The study demonstrates that human MSCs affix to the injury site and influence spinal cord cells to accelerate the repair process. ... Our results indicate that MSC therapy not only augments recovery after spinal cord injury, but also accelerates the recovery time"

Thursday, October 6, 2011
Via ScienceDaily: "Glioblastoma is one of the most aggressive forms of brain cancer. Rather than presenting as a well-defined tumor, glioblastoma will often infiltrate the surrounding brain tissue, making it extremely difficult to treat surgically or with chemotherapy or radiation. ... [scientists] developed a method to combine a tumor-homing peptide, a cell-killing peptide, and a nanoparticle that both enhances tumor cell death and allows the researchers to image the tumors. When used to treat mice with glioblastoma, this new nanosystem eradicated most tumors in one model and significantly delayed tumor development in another. ... This is a unique nanosystem for two reasons. First, linking the cell-killing peptide to nanoparticles made it possible for us to deliver it specifically to tumors, virtually eliminating the killer peptide's toxicity to normal tissues. Second, ordinarily researchers and clinicians are happy if they are able to deliver more drugs to a tumor than to normal tissues. We not only accomplished that, but were able to design our nanoparticles to deliver the killer peptide right where it acts - the mitochondria, the cell's energy-generating center. ... In this study, our patients were mice that developed glioblastomas with the same characteristics as observed in humans with the disease. We treated them systemically with the nanoparticles. Once the nanoparticles reached the tumors' blood vessels, they delivered their payload (a drug) directly to the cell's power producer, the mitochondria. By destroying the blood vessels and also some surrounding tumor cells, we were able to cure some mice and extend the lifespan of the rest,"

Wednesday, October 5, 2011
MItochondrial function, structure, and damage are clearly important to longevity, both within and between species, so it should be no surprise to find mitochondrial DNA haplogroups associated with variations in human longevity: "Human longevity is a complex heritable genetic trait. Based on substantial evidence from model organisms, it is clear that mitochondria play a pivotal role in aging and lifespan. However, the effects that mitochondrial genome variations have upon longevity and longevity-related phenotypes in Zhuang people in China have yet to be established. By genotyping 15 variants for 10 haplogroups in 738 Zhuang subjects, including 367 long-lived individuals and 371 controls, we found that haplogroup F was significantly associated with longevity in females of Zhuang population of China. Additionally, haplogroup F was related to higher HDL levels in long-lived individuals. Further analysis suggests that the non-synonymous variant m.13928G>C in haplogroup F was also associated with longevity in female Zhuang Chinese which might account for the beneficial effect of F."

Wednesday, October 5, 2011
The Volokh Conspiracy on the correlations between health and wealth in a region, a connection with compelling evidence both before and after the Industrial Revolution: "for most of history, gains in human life expectancy were made at the beginning, not the end of life. It is true that older people have always been part of society, but they were less numerous and more weathered than today's seniors. ... But that is not the end of the story. Rather, it is the beginning of a new chapter where humanity takes on ill health and death at later ages. Indeed, those efforts have already had an impact on the growth of life expectancy. ... For many years, it's been clear that there is a positive correlation between health and wealth, but it was most commonly thought that wealth creates health. While it is certainly true that the rich can afford to take better care of themselves, it is now known that health also begets wealth. Put another way, poor health causes a decline in productivity for the simple reason that it's very difficult to work effectively when you're in ill health, thereby increasing the chances of falling into poverty. ... based on the available research, if there are 'two countries that are identical in all respects, except that one has a 5 year advantage in life expectancy,' then the 'real income per capita in the healthier country will grow 0.3-0.5% per year faster than in its less healthy counterpart.' While these percentages might look small, they are actually quite significant, especially when one considers that between the years of 1965 to 1990, countries experienced an average per capita income growth of 2% per year. When countries only have an average growth of 2%, an advantage of 0.5% is quite the boost. Now, those numbers are based only on a 5 year longevity advantage. What if a country had a 10, 20, or 30 year advantage? The growth may not continue on a linear basis, but if the general rule holds - a jump in life expectancy causes an increase in economic growth per capita - then having a longer-lived population would facilitate enormous differences in economic prosperity."

Tuesday, October 4, 2011
An unpleasant conjecture outlined via EurekAlert!: "The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research ... Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease. The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's. ... Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease. ... We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain. The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure." It's probably best not to get too worked up about this sort of thing, concerning though it is. Many conditions can be made to be transmissible through the intervention of biotechnology, but that doesn't mean they are normally so in any meaningful way, and the prion diseases are not easy to transmit. The assumption at this point, based on the weight of evidence, should still be that Alzheimer's is something that in the vast majority of cases your body does on its own, and you bear a level of risk strongly associated with your lifestyle choices.

Tuesday, October 4, 2011
From FuturePundit: "Myelin is insulation around nerves and is essential for the conduction of impulses along nerves. The ability to grow pure populations of cells that make myelin brings us closer to effective treatments for multiple sclerosis and other diseases characterized by the loss of myelin. ... Scientists [found] a way to rapidly produce pure populations of cells that grow into the protective myelin coating on nerves in mice. Their process opens a door to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases afflicting millions of people worldwide. ... These results matter to us all. Why? We all suffer from a demyelinating disease called aging. One of the reason older folks have harder times with memory recall, coordination, and other mental tasks is that myelin deteriorates with age. The ability to restore myelin is an essential rejuvenation therapy. Therefore the pursuit of effective treatments for MS and other demyelinating diseases will yield useful therapies for brain rejuvenation. Just about any therapy aimed at repairing damage caused by a specific disease will also be useful for rejuvenation. Aging causes very diffuse damage to all the tissues in the body. When enough of that damage accumulates in a single organ or structural element disease emanating from a specific location emerges. But the localized disease is really just part of a bigger pattern of damage accumulation. So therapies aimed at repair of specific locations in the body will have a great deal of overlap with therapies aimed at full body rejuvenation."

Monday, October 3, 2011
An increasing weight of evidence links ongoing to damage to blood vessels in the brain with loss of cognitive ability as people grow older. Here is another example: "Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. ... For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. ... We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. ... Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning." The only practical, widely available ways to slow down blood vessel aging at the present time are exercise and calorie restriction, but future therapies - such as those built upon the SENS platform - will have to do better and actually reverse damage in the old.

Monday, October 3, 2011
Here's a popular press article that discusses the concept of actuarial escape velocity: "Someone you know could live to be 1,000 years old, according to Aubrey de Grey ... Even for people in good health, cells become damaged through the course of a human life, de Grey said. It's a solvable problem, he said, by providing maintenance to damaged cells. He cited stem cell research and using bacteria as possible means of restoring cells to their youthful state, which would lengthen life - perhaps infinitely. 'It's all about restoring organs and tissue to the way it was before it suffered some sort of damage,' he said, comparing the process to the maintenance that can keep cars running for decades.The research that could lead to these techniques is further along than most people realize, de Grey said, and could begin providing therapies within the next 25 years. Or not, he added, but the possibility exists that today's 20-somethings could be alive in 3011. Not only would they be alive, but they'd be able to live well, he said. The progress toward treatments that can provide such longevity will be incremental, though. The therapies that might exist in 25 years may restore a 90-year-old's body to a 60-year-old's health, but would not extend life indefinitely, he said. The key is reaching what de Grey called 'longevity escape velocity' - the rate of aging combined with the rate of the medical advancements that will prolong life to before-unthinkable lengths. An 80-year-old in 2011 hasn't much hope of living forever, he said, but the younger a person is, the better their chances of living in an age when drastically age-prolonging therapies exist."



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