An accumulation of advanced glycation endproducts (AGEs) is one of the changes thought to be a root cause of aging. The research quoted below is only a correlation, but there is plenty more where this came from to back up the viewpoint of AGEs as a contributing cause of aging: "Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. ... We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. ... Older adults with high pentosidine level had worse baseline DSST score but not different 3MS score. On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile ... [Thus] high peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21900628

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

Somewhere in the world, someone today pushed out the boundaries of what can be done with stem cells in medicine. The field is now so large and well funded that noteworthy advances are rolling in every week, and for each incremental step forward that you read about in the popular science press there are another half a dozen more behind the scenes, achieved without much commentary outside the scientific community. This is what a healthy field of research and development looks like: a lot of movement, a great deal of progress. Here are pointers to a few recent items, representative of what is taking place day in and day out around the world:

New Transplant Method May Eliminate Need for Lifelong Medication

The study found that a combination of two drugs lengthened survival time and prevented liver rejection in rodents. One drug was a low dose of tacrolimus, which prevented immediate rejection of the transplant, and the other was plerifaxor, which freed the recipient's stem cells from the bone marrow. The bone marrow cells freed by plerifaxor then traveled to the damaged liver and repopulated it with the recipients' own cells, replacing the donor cells that cause rejection. The stem cells also appeared to control immune response by increasing the amount of regulatory T-cells. Essentially, the scientists said they transformed the donor liver from a foreign object under attack by the immune system into an organ tolerated by the body within three months of the surgery. And - the rats only had to take the medications for one week after the transplant.

100-fold increase in efficiency in reprogramming human cells to induced stem cells

Researchers from the Wellcome Trust Sanger Institute have today announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate. Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors [retinoic acid receptor gamma (RAR-?) and liver receptor homolog (Lrh-1)], Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.

Regenerating eyes using cells from hair

Limbal stem cell deficiency (LSCD) [is] a condition which causes the cornea to become cloudy and develop a rough surface causing pain and leading to blindness. Currently, treatments focus on harvesting limbal cells from a patient's healthy eye or from cadaveric tissue. In her pioneering research, Dr. Meyer-Blazejewska considered the potential use of stem cells harvested from hair follicles to reconstruct damaged tissue for patients who suffer from LSCD in both eyes. ... Dr. Meyer-Blazejewska's team demonstrated that in the right microenvironment stem cells from hair follicles do have the capacity for cellular differentiation, the process whereby a less specialized cell becomes a more specialized cell type, in this case the cells of the corneal epithelial phenotype. The team's results showed an 80% rate of differentiation in mouse eyes following a cell transplant highlighting the promising therapeutic potential of these cells.

Stem-Cell Clinical Trials Move Debate Beyond Labs

Next year, Pfizer Inc. and a clutch of British scientists hope to join a small but growing group of researchers conducting the first clinical trials in one of the more contentious areas of science: medical treatments derived from human embryonic stem cells. Pfizer and its partners at University College London's Institute of Ophthalmology are awaiting regulatory permission to begin a human study in the U.K. of a possible treatment for age-related macular degeneration, a common disorder in the elderly that can cause blindness.

The constant hum of progress from the field of stem cell science and development is what we'd like to see emerging from work on aging and longevity science - and needless to say we don't. There are not enough researchers, and there is not enough funding, and there is not enough popular support to build this sort of pace of progress at the present time. That is what we must strive to change.

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

Just as the research community is sifting the world for correlations between variations in the human genome and variations in human longevity, so too are scientists beginning to pay greater attention to the role of the epigenome. 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?

A paper from earlier this year claims epigenetic biomarkers of longevity in nematode worms, a much simpler animal to study than we mammals:

Why do some individuals live longer than others? ... Inter-individual variation in human longevity has not been found to be under substantial genetic control, with heritability generally between 15% and 30% ... The situation is thrown into relief in studies of C. elegans, in which genetically identical siblings reared in identical environments usually experience different lifespans. In this work, we show that physiological differences between identical animals begin to appear relatively early in life and that markers of ill health in young adulthood presage shorter lifespans.

Using fluorescent markers to examine the level of activation of several genes, we found three regulatory microRNA genes [in] which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA "biomarkers of aging" act upstream in insulin/IGF-1-like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan.

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.

Interestingly, it looks like there are good signposts on that road; we shall no doubt see how good or useful epigenetic biomarkers turn out to be in humans. Certainly a large community of researchers are hotly engaged in trying to uncover truly reliable biomarkers that measure aging or predict longevity, so if there is something to be found in the epigenome they will eventually find it.

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

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."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21948108

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

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."

Link: http://extremelongevity.net/2011/10/04/vigorous-daily-exercise-linked-to-extreme-male-longevity/

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

As I might have remarked upon back in the Fight Aging! archives, 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.

there are a great many unrealistic viewpoints in the world that would hinder or halt longevity research, either directly or indirectly. Viewpoints like "the more regulation the better", "prove that you will do no harm at all before we'll let you move forward," or "let us redistribute all property and remove incentives for success and progress, for inequality for any is worse than death for all" spring to mind. In this latter context, "social justice" is a particularly pernicious phrase, being a shorthand for forceful redistribution of wealth by government fiat - institutionalized theft, aimed exactly at the point at which it will do the greatest damage to progress by removing incentives for success.

The world works this way: we can labor and trade to move everyone ahead, benefits for all and inequalities for all, or we can redistribute what presently exists - which at best leads to stagnation and no progress, and at worst becomes a repetition of Soviet era Russia and Eastern Europe. In both cases, inequality will be there - you can't kill it. The choice is whether it's inequality in comparative wealth or inequality in poverty, disease and rubble. Progress is absolutely dependent on freedom and the incentives of wealth earned through hard work and invention.

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 horded, restricted to the rich, tearing the world asunder, turning brother against brother, and causing cats to lie with dogs.

But aging and longevity has a lot of baggage, it seems. So I see that Sonia Arrison, blogging on radial life extension at the Volokh Conspiracy, took some time early on to address the standard nonsense on class warfare and social justice style "equality":

Could class conflict or even warfare break out over life-extension technologies? It is true that technology is rarely adopted by everyone at the same time, and when life-extending science hits the market, it will almost certainly be used by the wealthy first. ... New technologies are almost always adopted by the rich first, but over time they eventually reach everyone, and the historical record shows that the distribution of new technology is speeding up, not slowing down. For instance, it took forty-six years for one-quarter of the population to get electricity and thirty-five years for the telephone to get that far. It took only sixteen years, however, for one-quarter of American households to get a personal computer, thirteen years for a cell phone, and seven years for Internet access. A more vital example may be AIDS drugs which started off costing about $30,000 per patient per year 15 years ago. Now, better drugs are available and cost $100 per patient. ... The fact that the first users of life-extending technologies will tend to be wealthy increases the chances that the technologies will thrive and eventually reach everybody. Without private investors who believe in the value of a new product and want to support its development, many great ideas would be stillborn. History bears this out, from Queen Elizabeth owning some of the first silk stockings, to wealthy New Yorkers paying $20 in 1915 for a three-minute phone call to San Francisco.

I've long thought it rather sad that so much of our society is bludgeoned into the chattering classes' view of everything laid out in terms of class, conflict, redistribution, forced organization in a top-down fashion, and all the other unfortunate ideals that come with strong centralization of power. Their viewpoints are completely divorced from any sensibility as to how progress actually occurs, or how wealth is in fact created. They are thus one of the first barbarians hammering at the gate: people ignorant of the causes of the success of their society, yet still wealthy enough to be somewhat shielded from the immediate consequences of such ignorance. It never lasts forever, of course: in the end this will come to the same sorry end as Rome or the British Empire, and the US will become a shell of what it once was, a population living amidst the ruins of past grandeur, so constrained by their government as to have forgotten how to achieve greatness and prosperity once again.

The only silver lining is that scientific knowledge is no longer lost alongside the roots of wealth and prosperity; the world has become too small for that, and knowledge will move to the places where it can be best preserved. So those glories, at least, will continue even when the research community that produced them can no longer be sustained.

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