Stem cell populations in the body live in stem cell niches, each different type of stem cell with its own niche. The niche supplies the necessary environment and many of the cues that direct stem cell activity, and this is why changes in the niche are possibly more important than changes in stem cells themselves when it comes to the decline of stem cell activity with aging. That decline causes a sort of corrosion of your tissues as stem cells increasingly fail to keep up with maintenance and repair - but the evidence to date suggests that those stem cells are generally still capable of doing their jobs, provided they are given their marching orders:

Surprisingly, this age-related decline in stem cell potency may be somewhat reversible. A team of Howard Hughes Medical Institute (HHMI) researchers has found that in old mice, a several-week exposure to the blood of young mice causes their bone marrow stem cells to act "young" again. ... The researchers have not yet isolated the blood-borne factors that can switch old stem cells back to a more youthful state, but their results are consistent with other recent studies that show stem-cell aging may be reversible.

Thus we have to look at the aging of stem cells in the context of the niche and the rest of the body, and we have to look at regenerative medicine for the old in a holistic way. While throwing stem cells at every problem seems to be fairly beneficial, based on the successes to date in first generation stem cell transplant therapies, it isn't enough in and of itself. Putting good stem cells into an age-damaged environment is not using them to their best effect.

But this all comes back to the question of just what a stem cell niche is anyway, and why the changes of aging change the way in which stem cells act within the body. Here is a good open access paper that provides an introduction to the niche and its importance, with some examples of various different stem cell and niche types throughout the body:

What does the concept of the stem cell niche really mean today?

Ideas about stem cells, and how they behave, have been undergoing a lot of change in recent years, thanks to developments in visualizing, monitoring, and manipulating cells and tissues. ... the detailed mechanisms underlying niche function are extremely varied. Niches may be composed of cells, or cells together with extracellular structures such as the extracellular matrix (ECM). They may be sources of secreted or cell surface factors [that] control stem cell renewal, maintenance, or survival. They may consist of just a single cell type, or a whole host of interacting cells. They may derive from cells outside the stem cell's lineage, or they may derive primarily from the stem cell's own descendents. In general, there seems to be much more consensus about the fact that stem cells invariably need niches than about the specific mechanisms by which niches do their jobs.

Why should a stem cell need a special environment? This is a pertinent question, given that none of the elementary processes that stem cells rely upon - growing, dividing, differentiating - are unique to stem cells. We can easily imagine three classes of answers:

One possibility is that there are demands placed on stem cells that necessitate special support for viability. For example, the need, imposed by cellular immortality, to minimize the accumulation of genetic damage, may drive stem cells to adopt a peculiar metabolic state that might force them to rely upon other cells nearby for sustenance. This 'nutritive' function of the niche remains a formal possibility, but in most systems few experimental data in support of it have so far emerged.

A second possibility is that niches are agents of feedback control. Recent studies tell us that stem cell pools are not slavishly maintained at a constant size by fixed, asymmetric divisions, but are usually capable of expanding or contracting and, even under homeostatic conditions, may face large stochastic fluctuations. The varied growth factors and cell surface molecules produced by niche cells may share the common goal of controlling stem cell pools. If this is the case, then the niche might best be thought of not simply as an environment conducive to stem cell functioning, but as an apparatus for communicating information about the state of a tissue back to the stem cells that maintain it. An important question to address would then be how niches obtain and relay such information.

A third possibility is that niches are instruments of coordination among tissue compartments. Some of the best evidence for this view comes from work on the hair follicle niche ... There, stem and progenitor cells responsible for maintenance of epidermis, pigmentation, hair, and connective and adipose tissue all interact in close proximity. A need to achieve tight coordination among these different cell populations may be the overriding reason for complex organization of this niche. The possibility that other niches may also be hubs of inter-lineage coordination is certainly an idea worth investigating.

The best case scenario for the future is that enacting the Strategies for Engineered Negligible Senescence to repair the known forms of cellular and molecular damage that occur with aging will cause stem cell niches to largely take care of themselves. In other words, under this scenario it turns out that the second possibility outlined in the quote above is the principal role for niches, and thus repairing the biological damage of aging in the body will cause the command and control mechanisms for stem cell populations to return to a youthful state.

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

Damaged mitochondria cause problems because their electron transport chains, the core mechanism by which they generate power for the cell, stop working the right way. That leads to a situation in which sub-par mitochondria in a cell are not recycled despite being damaged, and since they replicate like bacteria the bad mitochondria take over the cell. It goes downhill from there, and this whole process is one of the fundamental causes of aging. Ways of addressing this situation include repairing the mitochondria directly or working around their damage by creating replacements for the damaged parts of mitochondrial protein machinery elsewhere in the cell. Here is another line of research that looks at trying to minimize the consequences of that damaged machinery by providing substitute components, but with a different focus: "Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. ... This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22419586

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

Just as physical exercise is beneficial, so too is exercising the mind. This open access paper examines structured mental exercise as a basis for therapy that might do at least some good for neurodegenerative disease patients: "Non-pharmacological intervention of memory difficulties in healthy older adults, as well as those with brain damage and neurodegenerative disorders, has gained much attention in recent years. The two main reasons that explain this growing interest in memory rehabilitation are the limited efficacy of current drug therapies and the plasticity of the human central nervous system and the discovery that during aging, the connections in the brain are not fixed but retain the capacity to change with learning. Moreover, several studies have reported enhanced cognitive performance in patients with neurological disease, following non-invasive brain stimulation [i.e., repetitive transcranial magnetic stimulation and transcranial direct current stimulation to specific cortical areas]. The present review provides an overview of memory rehabilitation in individuals with mild cognitive impairment and in patients with Alzheimer's disease with particular regard to cognitive rehabilitation interventions focused on memory and non-invasive brain stimulation. Reviewed data suggest that in patients with memory deficits, memory intervention therapy could lead to performance improvements in memory, nevertheless further studies need to be conducted in order to establish the real value of this approach."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297818/

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

The industry that provides antioxidant supplements to the world has tremendous inertia: enormous income and a very loud voice, and thus little incentive to react to advances in scientific knowledge that might reduce that revenue stream if acted upon. So despite the scientific consensus that ingested antioxidants are not in fact wonderful for your health, and may even be modestly harmful over the long term, the larger players in the industry continue onward as though it's still 1992 outside their offices.

On the other side of the fence, the public at large keeps buying the products as though it's still 1992, just as blithely ignoring what the scientific community has to say on the matter. Everyone wants that silver bullet to be available now rather than tomorrow, and wants it badly enough to buy lead painted up to a nice sheen if that's all there is. All in all it's a good reminder that any institutional knowledge or common wisdom is likely to be a decade or two out of date - it takes time for information to percolate, even in this age of instant electronic overcommunication. There is seemingly so much that everyone has to say, day in and day out, and yet the important data still takes years to get from point A to point B.

Here is a good open access paper on antioxidants and just how far removed from reality the common wisdom is these days. I imagine it will take a few more years of authoring similar review papers for the point to start to sink in:

Antioxidants are assumed to provide numerous benefits, including better health, a reduced rate of aging, and improved exercise performance. Specifically, antioxidants are commonly "prescribed" by the media, supplement industry, and "fitness experts" for individuals prior to training and performance, with assumed benefits of improved fatigue resistance and recovery. This has provoked expansion of the supplement industry which responded by creation of a plethora of products aimed at facilitating the needs of the active individual. However, what does the experimental evidence say about the efficacy of antioxidants on skeletal muscle function? Are antioxidants actually as beneficial as the general populous believes? Or, could they in fact lead to deleterious effects on skeletal muscle function and performance?

...

Experimental evidence does not support the "common knowledge" that antioxidant treatment greatly improves exercise performance and recovery. On the contrary, studies with antioxidant supplementations generally show no effect on muscle function during and after exercise.

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

Less fat tissue is unambiguously good for you over the long term, and one side effect of calorie restriction is the loss of excess fat tissue - but that is only a side effect. More interesting stuff is going on at the level of cells and their mechanisms: "Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis [was] performed on both WAT and BAT from nine month old male rats fed ad libitum or subjected to CR for six months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR." It is worth noting that there are other signs that the biochemistry of fat tissue, and its effects on health, can be dramatically altered - see the research on fat in GHRKO mice, for example.

Link: http://www.ncbi.nlm.nih.gov/pubmed/22414572

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

One of the underlying mechanisms by which the advanced glycation endproducts (AGEs) that build up with age cause harm is through hammering on the receptor for AGEs, or RAGE. Some Alzheimer's researchers are looking into targeting RAGE in order to remove the contribution of AGEs to that condition, and it is possible that the results of their work may have more general application to AGEs in aging - though the best possible strategy would be to remove the AGEs rather than work around them: "Researchers have taken another crack at a promising approach to stopping Alzheimer's disease that encountered a major hurdle last year. ... scientists have developed a compound that targets a molecular actor known as RAGE, which plays a central role in mucking up the brain tissue of people with the disease. Scientists [synthesized] a compound that stops RAGE in mice - reversing amyloid deposits, restoring healthy blood flow in the brain, squelching inflammation, and making old, sick mice smarter. But the scientists caution that the work has a long way to go before it's considered as a possible treatment in people. ... A phase 2 study in 399 people of another compound designed to stop RAGE - which stands for Receptor for Advanced Glycation Endproducts - was halted prematurely in November when scientists had questions about the compound's safety at high doses, and after early results indicated that the compound was not helping patients with Alzheimer's disease. ... The benefits of blocking RAGE are even greater than has been realized. RAGE is central to many mechanisms that wreak havoc in the brains of people with Alzheimer's disease. It turns out that when you inhibit RAGE, you block molecules central to creating inflammation in the brain, and that is a major problem with Alzheimer's disease."

Link: http://www.urmc.rochester.edu/news/story/index.cfm?id=3440

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

A billion people will die between now and the earliest plausible date for the first package of rough and ready but working rejuvenation therapies - say twenty years from now. Another few decades will pass for the technology to work its way out to global availability at low cost, and the deaths by aging will continue in less fortunate regions while this happens. Even after aging is completely conquered, there will be an ongoing toll of death due to accidents and whatever passes for disease in the age of medical nanotechnology. Death isn't going away completely for we biological folk, no matter how well we do in the field of medicine in the foreseeable future: medicine can't wave away falling rocks.

Thus will always be a role for what we might term post-mortem critical care: technologies and services to preserve the fine structure of the brain and the mind it contains following death, and keep them preserved until such time as that patient can be restored to life. At present the only post-mortem critical care option is cryonics, with what looks like a fair few years to wait for technology to advance to the point of restoration, and thus an unknown chance of eventual success for any individual - but a significantly greater chance than is offered by the grave, of course. In contrast, in a future in which the technology to restore a preserved person exists, cryonics and other preservation technologies like plastination will occupy a more dynamic position in the medical toolkit, and patients might expect to wait in a preserved state only for transport to the nearest major population center.

At last year's SENS5 conference, Max More, CEO of cryonics company Alcor, gave this presentation on the future of his industry:

Cryonics involves the cryopreservation of humans as soon as possible after legal and clinical "death". Legal and clinical death differ importantly from biological death or true (irreversible) cessation of function. It is therefore a mistake to portray cryonics as an alternative to cremation or burial. It is true that cryopreserved people are not alive but neither are they dead. Cryonics should be seen as part of the field of life extension. Cryonics enables the transport of critically ill people through time in an unchanging state to a time when more advanced medical and repair technologies are available. Even after "longevity escape velocity" has been attained and aging has been largely tamed, cryonics will continue to be needed for people who die of accidents or diseases for which there is no cure at the time.

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

Here is a study claiming a noticeable impact on mortality rates from eating red meat. Weight is considered to some degree via body mass index, but I have to wonder if this only reflects a modest association of red meat consumption with other, less healthy lifestyle choices rather than an actual red-meat-based mechanism - as an obvious candidate mechanism for that isn't also present in all meat consumption isn't springing to mind: researchers "found that red meat consumption is associated with an increased risk of total, cardiovascular, and cancer mortality. The results also showed that substituting other healthy protein sources, such as fish, poultry, nuts, and legumes, was associated with a lower risk of mortality. ... [Researchers] observed 37,698 men from the Health Professionals Follow-up Study for up to 22 years and 83,644 women in the Nurses' Health Study for up to 28 years who were free of cardiovascular disease (CVD) and cancer at baseline. Diets were assessed through questionnaires every four years. ... One daily serving of unprocessed red meat (about the size of a deck of cards) was associated with a 13% increased risk of mortality, and one daily serving of processed red meat (one hot dog or two slices of bacon) was associated with a 20% increased risk. ... These analyses took into account chronic disease risk factors such as age, body mass index, physical activity, family history of heart disease, or major cancers. ... Replacing one serving of total red meat with one serving of a healthy protein source was associated with a lower mortality risk: 7% for fish, 14% for poultry, 19% for nuts, 10% for legumes, 10% for low-fat dairy products, and 14% for whole grains. The researchers estimated that 9.3% of deaths in men and 7.6% in women could have been prevented at the end of the follow-up if all the participants had consumed less than 0.5 servings per day of red meat."

Link: http://www.sciencedaily.com/releases/2012/03/120312162746.htm

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

Via ScienceDaily: researchers "have made early retina structures containing proliferating neuroretinal progenitor cells using induced pluripotent stem (iPS) cells derived from human blood. And in another advance, the retina structures showed the capacity to form layers of cells - as the retina does in normal human development - and these cells possessed the machinery that could allow them to communicate information. ... Put together, these findings suggest that it is possible to assemble human retinal cells into more complex retinal tissues, all starting from a routine patient blood sample. Many applications of laboratory-built human retinal tissues can be envisioned, including using them to test drugs and study degenerative diseases of the retina such as retinitis pigmentosa, a prominent cause of blindness in children and young adults. One day, it may also be possible replace multiple layers of the retina in order to help patients with more widespread retinal damage. ... We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain."

Link: http://www.sciencedaily.com/releases/2012/03/120313185232.htm

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

This is an era of data in the sciences - endless, vast stores of data, with more pouring in constantly from new studies. In most fields the infrastructure to manage that data is still under construction; in the life sciences, for example, the rapid advance of bioinformatics and biotechnology in general has outpaced the strategies for data management. The data infrastructure is lacking, even as it is being built up rapidly. This has consequences on the efficiency of research and the speed of progress, but researchers are not blind to this present state of affairs.

Here, for example, Maria Konovalenko of the Science for Life Extension Foundation presents at last year's SENS5 conference, calling for better and more systematic management of data in longevity research initiatives - which is effectively a form of advocacy for lowering the cost of exchange of information between research groups.

Traditionally evaluation of age-related changes is performed by physiological, functional and psychological tests, by visual examination and some biochemical analyses. There is a big gap between the molecular data of aging and their implementation in practice mainly because aging data is scarce and it gets lost in the stream of bio-medical knowledge. As we know only a few databases exist that concern the molecular aspects of aging and none of them describes age-related changes and phenotype context like cell type or tissues.

We propose creation of an open web-based Integrated Information System on Aging Biomarkers. The goals of the System: 1. Systematization of data on age-related changes happening on various levels of organization in humans and model animals 2. Systematization of experimantal data on interventions in aging processes in model animals 3. Integration of clinical data on the impact of various interventions on aging processes in patients 4. Creation of a basis for modeling of aging processes, therapeutic interventions and their impact on patients' health and longevity

When development of life extending therapies begins in any earnest way (as opposed the present expensive dabbling with metabolic manipulation to slightly slow aging), it will be necessary to start keeping score and measuring well. Even before then, and as I pointed out above, there is more data than can easily be made useful at this time - that has to change in order to build a better foundation for the next generation of research projects.

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