Fight Aging!

FIGHT AGING! NEWSLETTER
January 23rd 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!

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CONTENT

- SENS5 Video: Neuron Replacement in the Neocortex
- Wasted and Sidelined Efforts
- Contemplating Our Microlives
- Evidence Against the Late-Life Mortality Plateau
- Discussion
- Latest Headlines from Fight Aging!

SENS5 VIDEO: NEURON REPLACEMENT IN THE NEOCORTEX

Another presentation is posted from last year's SENS5 conference:

https://www.fightaging.org/archives/2012/01/sens5-video-neuron-replacement-in-the-neocortex.php

"The cerebrum, as the substrate for our consciousness, memories, personality, and self-identity, presents unique challenges for regenerative medicine. Regenerative approaches must not only maintain general cerebral function, but also preserve as much as possible the details of the wiring and firing parameters that define each individual. A combination of molecular repair and gradual cellular replacement appears most likely to succeed. Toward this end, we are establishing paradigms in mice for replacing glutamatergic projection neurons in the neocortex, seat of our highest cognitive functions.

"Any strategy for using transplanted cells for neocortical cell replacement is currently hampered by the inability to get cells to disperse into the existing neural tissue. To overcome this issue, we will transplant at the edge of the neocortex highly migratory embryonic GABAergic precursor cells that are engineered with lentiviruses to transdifferentiate to a glutamatergic fate once they have dispersed throughout the neocortex."

WASTED AND SIDELINED EFFORTS

I note that a Life Extension Conference organized by Christine Peterson of the Foresight Insititute is coming up in a few months. In general I see this as a prime example of the disappointing direction sometimes taken by people who are nonetheless very much supporters of the best long term visions for engineered longevity. They step off the train and start focusing on what's right in front of our nose today, things that are shiny but generally useless - the syndrome of looking under the lamp-post for the lost keys because that's where the light is. So this conference is very much an "anti-aging" event, only a single step removed from those held by the American Academy of Anti-Aging Medicine (A4M).:

https://www.fightaging.org/archives/2012/01/wasted-and-sidelined-efforts-that-would-be-better-spent-on-sens.php

"If we want to continue developing and guiding nanotech and other advanced technologies in the decades to come, we need to apply our high-tech knowledge and judgment to keeping our own bodies and brains functioning optimally. Should we be eating and exercising differently, taking supplements, getting our DNA read and telomeres measured, using sleep-monitoring or stress-reduction devices? These are challenging questions with new information arriving continually - let's pool our efforts to come up with good answers."

The trouble with this sort of statement is that there's already one good answer with a massive weight of science behind it. That answer is that you should be practicing calorie restriction and exercising moderately on a daily basis, and everything else that people are trying to sell you as a way to meaningfully extend health and life now is a waste of time and money. No technology or technique that is presently available or in any danger of becoming presently available within the next decade can even begin to approach the demonstrated benefits of calorie restriction and regular exercise for a basically healthy individual of any age. The only practical way to do far better than this is to support and help speed research and development of the SENS program for rejuvenation biotechnology - or related repair-based technologies aimed at reversing the causes of aging. The future isn't here yet when it comes to engineered longevity, and if we want that future to happen then we have to help make it happen.

Making it happen means accepting that there are no silver bullets now and that we'll have to work hard to create those silver bullets in time to be used by our older, future selves. But that truth doesn't sell products and services here and now, so you're not likely to hear it said by too many of those involved in a conference whose purpose is to sell you on presently available products and services.

Should I be appreciative that someone is making a serious effort to produce conferences attractive to the "anti-aging" industry that are one step up from the garbage that populates A4M and similar conferences? Possibly. But as I've said a number of times in the past, if gaining the attention of the anti-aging industry actually worked as a method to advance the cause of real rejuvenation biotechnology, such as SENS, then it would have worked already - and long ago, given that the Life Extension Foundation, A4M, and others have been hoeing that row for longer than many of us have been alive. But it doesn't work: the billions of dollars that flow through the "anti-aging" marketplace do not lead to any meaningful level of support, understanding, education, or funding for real longevity science - beyond the funding for research offered by the LEF, all you'll hear is crickets. Interactions with that industry are a dead end until that fact changes.

CONTEMPLATING OUR MICROLIVES

Some thoughts on the urge to optimization insofar as it applies to health and longevity:

https://www.fightaging.org/archives/2012/01/contemplating-our-microlives.php

"I'm not a big fan of the optimization mindset when it comes to long term health and longevity. Like all forms of optimization, it makes for a great hobby - with the potential to turn into a massive sink of time and money if you head on all the way down the rabbit hole. Importantly, however, and unlike optimization hobbies that involve cars, games, and other easily measured items, you will never really know how well you are doing when it comes to your own life expectancy. It's extremely easy to get the 80/20 result: practice calorie restriction and exercise regularly. But beyond that, there's no real way to tell whether any of your more esoteric practices are helping, hindering, or doing more or less nothing. There is no meaningful scorecard for future remaining life expectancy that you can measure and check your optimization efforts against.

"This may well change over the next ten years, but for now it is what it is. By all means make health your hobby - it beats some of the other options in terms of general utility - but don't for one moment imagine that you actually know how well you're doing past the 80/20 point. And if you're not practicing calorie restriction, then it doesn't much matter what else you're doing because you haven't even captured all of the easy 80%."

EVIDENCE AGAINST THE LATE LIFE MORTALITY PLATEAU

Data in some lower animals shows that the character of aging changes in late life; for one, the risk of death per unit time stops increasing - which raises all sorts of interesting questions about what is going on under the hood. There were some hints that this might be the case in extremely old humans, but a recent work of statistical analysis suggests not:

https://www.fightaging.org/archives/2012/01/a-counterpoint-to-the-concept-of-the-late-life-mortality-plateau.php

"Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102-105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be artifacts of mixing together several birth cohorts with different mortality levels and using cross-sectional instead of cohort data. Age exaggeration and crude assumptions applied to mortality estimates at advanced ages may also contribute to mortality underestimation at very advanced ages."

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!

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LATEST HEADLINES FROM FIGHT AGING!

GENETIC SIGNATURES OF EXCEPTIONAL LONGEVITY IN HUMANS
Friday, January 20, 2012
https://www.fightaging.org/archives/2012/01/genetic-signatures-of-exceptional-longevity-in-humans.php
A bold set of claims from this group working on the genetics of natural variation in longevity for humans: "Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) ... Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages ... Further [analysis] suggests that 90% of centenarians can be grouped into clusters characterized by different 'genetic signatures' of varying predictive values for exceptional longevity. ... The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity." The researchers are claiming some moderately common sets of SNPs found in centenarians (but not so common in the general population) can predict exceptional longevity with odds of 70% or higher, with the much more predictive combinations of SNPs - some at 95% odds of exceptional longevity - being correspondingly very rare. The caveat here is that this is heavily statistical work, and we've already seen one paper from this group withdrawn last year for issues with the statistics.

THE IMPACT OF MEDICAL PROGRESS ON MACULAR DEGENERATION
Friday, January 20, 2012
https://www.fightaging.org/archives/2012/01/the-impact-of-medical-progress-on-macular-degeneration.php
An example of the world moving forward, even though the really flashy biotechnology is still in the laboratory rather than the clinic: "Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. A [report] shows the number of new cases of blindness and severe visual loss in Denmark has been halved during the last ten years. ... [Researchers] examined the records of 11,848 new cases of legal blindness. The rate of blindness from AMD fell from 522 cases per million inhabitants aged 50 years or older in 2000, to 257 cases per million in 2010, a reduction by over 50 per cent. The bulk of the decrease occurred after 2006, following the introduction of new effective treatment for wet AMD, which is characterised by leaking blood vessels having formed under the fovea. The treatment consists of repeated injections into the eye of a medication that inhibits the signalling molecule vascular endothelial growth factor (VEGF). ... The observations from Denmark were published together with a corroborating report from Israel that found comparable changes in the incidence of legal blindness in that country. ... The massive implementation of modern wet AMD therapy has been a challenge. It is therefore very important that we can now show an impact on public health and it is wonderful to see a reduction in severe visual loss."

ON THE IMPACT OF AGES IN THE DIET
Thursday, January 19, 2012
https://www.fightaging.org/archives/2012/01/on-the-impact-of-ages-in-the-diet.php
Advanced glycation end-products (AGEs) are implicated in aging - one of the forms of chemical gunk that accumulates in the body over time, harming the operation of intricate biomolecular machinery (in this case probably by triggering cells to respond in an undesirable way). AGEs are a part of our dietary intake as well as being generated in the body, and there is a debate over the degree to which dietary intake of AGEs is important in the pace of buildup over a lifetime - and the role of gut bacteria for that matter, given that they can independently produce AGEs as well. Here is a review paper on the subject: "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer's disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research."

DEVELOPING A DIAGNOSTIC PLATFORM FOR AGING
Thursday, January 19, 2012
https://www.fightaging.org/archives/2012/01/developing-a-diagnostic-platform-for-aging.php
A brief overview of one of the lines of work advocated by the Science for Life Extension Foundation: "Aging biomarkers are parameters that always, and in all people, change during aging. It is possible to evaluate and improve therapies that are aimed at slowing down aging, using the biomarkers of aging. The value and changing dynamics of aging markers provides information about the intensity of aging processes in the cells of the patient. Aging biomarker monitoring allows us not only to diagnose various diseases, but also to prevent their development. Aging can be slowed down. At the moment, there are already several scientific approaches that could lead to slowing down aging, and extending life. Scientists have been able to significantly extend the lifespans of model animals. Now, it is time to apply the biogerontology knowledge in clinical practice. To understand if a given therapy is effective or not, first of all we compile data via conventional clinical tests to create the 'electronic health passport.' After that, we can perform measurements of the aging biomarkers listed in the table. The indicators will inform us if the therapy is working. Soon we will be able to look at thousands of parameters, obtained using genome and transcriptome sequencing, epigenome mapping and analysis of proteome and metabolome. The additional data will make the anti-aging therapies more precise. ... view our entire booklet that lists twenty (20) aging bio-markers."

THERAPIES FOR REJUVENATION AND THEIR DELIVERY
Wednesday, January 18, 2012
https://www.fightaging.org/archives/2012/01/therapies-for-rejuvenation-and-their-delivery.php
An interview with Aubrey de Grey of the SENS Foundation: "I'm interested in making sure that none of [the forms of biological damage that cause aging] are left behind. ... the main reason why we prioritize certain things over others is simply if they are not being prioritized by the rest of the world. At the moment, [in] our Research Center in Mountain View, we are working on LysoSENS, as you said, but we are also working on MitoSENS, the elimination of mitochondrial mutations in aging, and ways to make those mitochondrial mutations harmless essentially by putting copies of the mitochondrial genome into the nuclear genome. And in projects that we are funding in university labs around the country, we are doing a number of other things relating to other aspects of SENS. So yes, we are interested in focusing on all of these things in parallel. ... So at the moment, there are just a few areas within SENS that we are de-prioritizing because they are being funded quite well elsewhere. One of them is the elimination of amyloids [that] occurs in Alzheimer's disease. And even there, it's only sort of that one subset of that one deadly thing that we are not working on. So we are working on something very similar, the accumulation of a similar type of garbage outside cells that occurs predominantly in the heart. It just turns out that even though Alzheimer's work is well-funded and well respected and everything, nevertheless during the same sort of approach for other types of amyloids, other types of extracellular garbage, it is not being particularly enthusiastically pursued by other people, so we are doing our bit. Similarly, in the case of lost cells where cells die and they are not automatically replaced by other cells or by the division of other cells - that is what stem cells are for. Stem cell therapy is very real - people are working in lots of areas in that field, so of course we are not trying to duplicate that effort. But even there, we are doing one of two things. For example, we're interested in a particular type of cell loss which is the shrinkage of an organ called the thymus, which is responsible for the creation of certain types of immune cells. It turns out that restoration of the thymus to its useful size is something that not many people work on. The approaches that have been tried have not been very successful. We are looking at some more ambitious but we think more promising approaches that have not been looked at by other people."

TELOMERES AND OSTEOARTHRITIS
Wednesday, January 18, 2012
https://www.fightaging.org/archives/2012/01/telomeres-and-osteoarthritis-1.php
Another telomere length correlation, adding data to a relationship known for some years: "A process linked to natural cell aging has now also been associated with knee osteoarthritis, researchers say. Telomeres - lengths of DNA on the ends of chromosomes, sometimes described as being like the plastic cap on a shoelace tip - naturally shorten with age, but can also shorten due to sudden cell damage. Abnormally short telomeres have been found in some types of cancer and preliminary research has suggested that the average telomere length is also shortened in osteoarthritis. In this new study, Danish researchers used new technology to closely examine the telomeres of cells taken from the knees of osteoarthritis patients who had joint replacement surgery. The cells had abnormally shorted telomeres and the percentage of cells with ultra-short telomeres increased with proximity to the damaged area in the knee joint ... The telomere story shows us that there are, in theory, two processes going on in osteoarthritis. Age-related shortening of telomeres, which leads to the inability of cells to continue dividing and so to cell senescence [deterioration], and ultra-short telomeres, probably caused by compression stress during use, which lead to senescence and failure of the joint to repair itself. We believe the second situation to be the most important in osteoarthritis. The damaged cartilage could add to the mechanical stress within the joint and so cause a feedback cycle driving the progression of the disease."

STRIVING TO FIND A MIDDLE GROUND THAT INCORPORATES BOTH DEATHISM AND THE URGE TO RADICAL LIFE EXTENSION
Tuesday, January 17, 2012
https://www.fightaging.org/archives/2012/01/striving-to-find-a-middle-ground-that-incorporates-both-deathism-and-the-urge-to-radical-life-extension.php
A possibly interesting position is put forth in this blog post, an attempt to merge a package of right to end of life decisions and acceptance of death with the urge to extend healthy life through biotechnology - an argument that the present cultural debate that places these two things in opposition is misguided: "People who try to fend off death are being selfish, are in denial, and are pouring money down the drain for cockamamy schemes to preserve their frozen heads for some fingers-crossed future, which will never arrive. At the same time, we shouldn't let people die, particularly (and ironically) if they really want to. Choosing death is untenable. It's against nature. No, death is good only when death decides it's ready for you. Or so go the arguments of many who oppose anti-aging technology. But just because we accept death as good and necessary, that doesn't necessarily mean we have to say the same about aging. Can we argue for anti-aging technology, for 2,000-year lifespans of perpetual youth, and admit death can be good at the same time? Not only can we; we must. We can accept death yet also seek to live vastly longer, healthier, and happier. Death is good, but so too is a long, long, long life. We can attain long lives of quality by rejecting extreme 'life-saving measures,' embracing euthanasia, and accepting that there are just some things we cannot cure. Death has got to be our closest kept enemy if we want to be ageless. Baffling as it may seem, wanting to live to be a thousand years old is inextricably connected to the ability to decide when it's time to give up the ghost." I can't say as I agree with the rush to incorporate acceptance of death, but I'm certainly very much on the side of the right to choose when and how you die. One of the many great and horrible cruelties in our present culture is the sadistic enforcement of prohibition against the choice of euthanasia - not least because it is the source of most of the challenges and costs that attend the organization of a successful cryopreservation.

LONGEVITY-RELATED GENES KEEP ROLLING IN
Tuesday, January 17, 2012
https://www.fightaging.org/archives/2012/01/longevity-related-genes-keep-rolling-in.php
The pace has picked up for discovery of longevity-correlated genetic and epigenetic variations in humans; there are too many for each and every new publication to be noted individually here - and we should expect there to be, ultimately, a very great many minor correlations between genes and natural variations in longevity. Here is an example: "The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. ... The expression of 360 probes was found to change differentially with age in members of the long-lived families [and] we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters."

A GENERAL INTEREST ARTICLE ON CALORIE RESTRICTION
Monday, January 16, 2012
https://www.fightaging.org/archives/2012/01/a-general-interest-article-on-calorie-restriction.php
From the Globe and Mail: "Brian Delaney, the president of the North Carolina-based Calorie Restriction Society International, is 48 years old, but he may as well be 25. Mr. Delaney, co-author of the book The Longevity Diet, began practising calorie restriction nearly two decades ago. He attributes his remarkably youthful condition to his active lifestyle and diet of less than 2,000 calories a day, compared with his prerestriction diet of about 3,000 calories a day. (Three thousand calories a day is on par with Health Canada's estimated energy requirements for active 19- to 30-year-old men.) As a participant in a calorie restriction study at the Washington University in St. Louis, he's had a variety of biomarkers measured, such as blood pressure levels, fasting glucose levels, cholesterol, DNA damage and arterial elasticity, and the results are typical of someone at least 20 years younger. ... 'I don't look 25. ... I look a little bit younger than I am,' he acknowledges, but those test results, he says, provide validation for limiting what he eats. In recent years, as calorie restriction has gained legitimacy, Mr. Delaney's society, which he helped create in 1994, has recorded a surge in membership. It now numbers roughly 2,500 members, including at least a few dozen based in Canada. 'We've seen a huge amount of growth in the last three or four years,' he says, 'and that's primarily because ... there have been a lot of new [human] studies coming out that confirm what most of us believed, based on past studies with laboratory animals.' ... It's impossible, however, for researchers to say whether calorie restriction can really lead to longevity in humans. That would require an unrealistically long study. But when it comes to 'secondary aging,' which is all the diseases associated with age and obesity, such as diabetes, cardiovascular disease, hypertension and some forms of cancers, [there's] no question that you would delay the occurrence of these diseases by calorie restriction."

SCIENTIFIC AMERICAN ON EPIGENETIC INHERITANCE OF LONGEVITY
Monday, January 16, 2012
https://www.fightaging.org/archives/2012/01/scientific-american-on-epigenetic-inheritance-of-longevity.php
Limited forms of Lamarkian inheritance, such as in the operation of metabolism, seem to be a reality, passed down through generations by epigenetic modifications. Here is a popular science article on the topic: researchers "described a series of experiments that caused nematodes raised under the same environmental conditions to experience dramatically different lifespans. Some individuals were exceptionally long-lived, and their descendants, through three generations, also enjoyed long lives. Clearly, the longevity advantage was inherited. And yet, the worms, both short- and long-lived, were genetically identical. This type of finding - an inherited difference that cannot be explained by variations in genes themselves - has become increasingly common, in part because scientists now know that genes are not the only authors of inheritance. There are ghostwriters, too. At first glance, these scribes seem quite ordinary - methyl, acetyl, and phosphoryl groups, clinging to proteins associated with DNA, or sometimes even to DNA itself. ... There is increasing evidence that epigenetic modifications are transgenerational (inherited through multiple generations) in a variety of species. Examples include coat color in mammals, eye color in Drosophila, symmetry in flowers, and now longevity in C. elegans. ... There seems to be a renewed acceptance for the Lamarckian concept (in limited cases). This could change our understanding of inheritance in that it would add another component, probably minor, but present, in addition to Mendelian genetics."

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