It's been a while since nanog was discussed here; it's one of the genes associated with early efforts to reprogram somatic cells into stem cells and seems to be important in the activity of embryonic stem cells. Here researchers are investigating the reversal of stem cell aging: "Although the therapeutic potential of mesenchymal stem cells (MSC) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of BM-MSC from adult donors. Microarray analysis showed that [expressing Nanog] markedly upregulated genes involved in cell cycle, DNA replication and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of [adult] BM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of [adult] BM-MSC to a similar level as that of neonatal BM-MSC. ... Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on BM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22949105

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

A couple of generally useful large reference studies on body weight, level of exercise, and resulting life expectancy and lifetime medical costs have shown up in recent years. As I'm sure you all know by now, the data all points in the direction of more fat and less exercise correlating with a shorter, less healthy life and higher lifetime medical costs. Take a look at these items, for example:

• Exercise, Longevity, and Long Term Medical Costs
• More Health, Longevity, and Medical Cost Data from the Ohsaki Cohort Study
• Another Look at the Economics of Inactivity

I recently noticed another, similar study on the Israeli population:

Health care costs per person were calculated by body mass index (BMI) by applying Israeli cost data to aggregated results from international studies. These were applied to BMI changes from eight intervention programmes in order to calculate reductions in direct treatment costs. Indirect cost savings were also estimated as were additional costs due to increased longevity of program participants. Data on costs and Quality-Adjusted Life Years (QALYs) gained from Israeli and International dietary interventions were combined to provide cost-utility estimates of an intervention program to reduce obesity in Israel.

...

On average, persons who were overweight (25 ? BMI < 30)had health care costs that were 12.2% above the average health care costs of persons with normal or sub-normal weight to height ratios (BMI < 25). This differential in costs rose to 31.4% and 73.0% for obese and severely obese persons, respectively.

I imagine that the popularity of this sort of work of late, or at least the increased willingness of funding bodies to make the necessary grants, has to do with a greater awareness of the impending financial collapse in medical entitlements and centralized health systems. This sad end is somewhat inevitable whenever a system is set up such that patients do not bear costs directly and funds are drawn from taxed resources - there will be overspending, waste, spiraling prices, special interests and all the other ugly aspects of business as usual in politics.

The "solution" offered up by the talking heads is, as usual, more control over everything: rationing, expensive attempts to influence lifestyle choices, and so forth. A far better option, and one unlikely to be tried until these systems have decayed into the sort of wasteland commonly associated with the ruins left at the end of the Soviet era, is simply to let people buy and sell medical services unmolested, unregulated, and in open competition. But that offers those in power few opportunities to advance their own position and line their own pockets, so as you can imagine it doesn't have many advocates where it matters. But ultimately the money runs out and the promises cannot be kept; if something cannot be paid for then it will not be paid for, regardless of how pretty the lies and promises might be.

So two lessons here: firstly, don't get fat and don't stay fat. Secondly, don't expect anyone to be paying your way in later life, regardless of what government employees might have to say on the matter.

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

A recent open access paper points to changing cytokine levels as a candidate mechanism for a range of conditions that occur with age and are generally made either worse or more likely by the presence of excess fat tissue. The link between being overweight and a higher risk of suffering the common age-related conditions is well known; chronic inflammation is thought to be an important mechanism here due to the way in which it impacts so many different systems in our biology, but the exact details are still open to debate.

Sarcopenia, obesity, and natural killer cell immune senescence in aging: Altered cytokine levels as a common mechanism

An inevitable consequence of human and rodent aging is sarcopenia - loss of muscle mass. Some muscle loss is due to physical inactivity, but even highly trained athletes lose muscle mass and strength with age. Although exercise programs can prevent and/or ameliorate sarcopenia, the effectiveness of exercise interventions to build muscle and effect metabolic improvements is less efficient in elderly subjects than in the young, due to multiple cellular and biochemical changes. ... Adipose tissue gain also is very common in aging and is a growing health concern for all ages. Visceral (abdominal) fat is of the greatest health concern because it is associated with insulin resistance, type 2 diabetes, cardiovascular disease, dementia, cancer, and overall mortality. ... Furthermore, obesity prevents muscle gain in response to functional overload [and] the combination of obesity and sarcopenia (so-called sarcopenic obesity) carries high health risks.

Another hallmark of aging is declining adaptive immunity, with complex alterations in innate immunity. Immune senescence is associated with mortality from all causes, including infectious diseases. Natural killer (NK) lymphocytes are innate immune cells that control intracellular infectious agents and cancers. In contrast to T and B lymphocytes, NK cell number is relatively increased in healthy aging and defects in NK cell function are subtle. However, declining NK cell number or function in aging is associated with death in the elderly. Therefore, mechanisms that preserve NK cell number and function may promote healthy aging.

To relate sarcopenia, obesity, and declining immunity in aging, we speculated that these conditions are linked processes, which are controlled by adipose tissue-derived and skeletal muscle-derived cytokines, known as adipokines and myokines, respectively

You can't really control the degree to which your immune system has been and will be hammered by various common herpesviruses, such as the near-omnipresent cytomegalovirus, but do you have a great deal of control over the fat tissue end of the relationship proposed in this paper. Letting yourself go to seed, getting fat and unfit, has consequences in the long term: a shorter, less healthy life with higher medical bills. Maybe science and those medical costs will dig you out of this hole before it kills you, but why roll those dice if you don't have to? The future of aging, health, and the biotechnologies of rejuvenation on the horizon is already uncertain enough for those of us in middle age today. Every extra year you can gain might make the difference between taking advantage of the first therapies to reverse aging and missing that boat entirely.

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

An interesting view on the evolutionary depths of longevity in mammals, achieved through analysis of presently available genomes: "It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters, and evolved into modern forms after dinosaurs went extinct, 65 Mya. The small size of most Mesozoic mammalian fossils essentially supports this view. Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here we use full-genome data to estimate the longevity and body mass of early placental mammals. Analysing 36 fully-sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics ... Linking these molecular evolutionary processes to life history traits in modern species, we estimate that early placental mammals had a life-span above 25 years, and a body mass above one kilogram. This is similar to current primates, cetartiodactyls or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution. Our results imply that long-lived mammals existed in the Cretaceous era, and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22949523

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

This interesting research result adds a little more to the debate over whether nuclear DNA damage is relevant to aging beyond its effects on cancer risk - though I think it's still a bit early to point to differences in DNA repair as the definitive cause of SIRT6-related longevity in mice: researchers "found that the decline in a cell's ability to repair DNA during aging coincided with a global reduction in the levels of proteins involved in the repair process. [They] tried to reverse the age-related decline in DNA repair efficiency by restoring the proteins to their original levels and found only one protein, SIRT6, did the trick. ... [Other research results have shown] that overexpressing the SIRT6 protein extended the lifespans of mice. Our research looked at DNA repair and found a reason for the increased longevity, and that is SIRT6's role in promoting more efficient DNA repair. ... The next step [is] to study the factors that regulate SIRT6, in an effort to learn more about the early stages of the DNA repair process. ... multiple groups are trying to develop drugs that activate SIRT6, and [researchers hope] that this research will one day lead to therapies that help extend a person's lifespan and treat cancer. ... SIRT6 plays a critical role in repairing the most dangerous type of DNA damage: double-strand breaks. DNA is a two-stranded molecule, and breaks can occur to one strand of the molecule or to both. In the case of single-strand breaks, the unbroken strand guides the repair process and the DNA molecule is typically restored to its original state. However, double-strand breaks, in which both strands are severed, are particularly hazardous because they are more difficult to repair and can lead to a rearrangement of the cell's genetic material."

Link: http://phys.org/news/2012-08-protein-dna-aging-cells.html

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

By way of following on from yesterday's thoughts on progress in longevity science, I'll point out that the August 2012 issue of Rejuvenation Research is available online. The leading editorial by Aubrey de Grey of the SENS Foundation covers much the same set of topics and is presently open access - so head on over and read it while that lasts.

What's Really Delaying the Defeat of Aging?

In the mid-1990s, when I decided to switch from computer science to gerontology, I recognized that the creation of a credible assault on aging would require solving three basic problems: (1) Creating a credible plan; (2) getting the people best placed to implement it to be interested in doing so; and (3) giving them the financial resources to get on with the job.

I broke the back of the first problem in mid-2000, when I realized that regenerative medicine - repairing the accumulating damage of aging - will probably be far simpler and easier to implement than the alternative followed by most biogerontologists, namely slowing the creation of that damage. By that time, I had also done most of the heavy lifting of item 2 (as I continued to do thereafter), by connecting with leading researchers worldwide, mostly face to face at conferences, and improving their understanding of how their expertise could be productively applied to aging. By way of illustration, quite a few of the most prestigious such people are named on the front cover of this journal as associate editors, and they accepted such a position for that reason. But what about item 3?

Unfortunately, I cannot tell so positive a story with respect to financial resources. Nearly a decade ago, I began to make public predictions of how soon we would achieve success in our crusade. I did so, as I still do, in the manner that (for better or worse) preoccupies the general public, namely in terms of longevity, but I have always been careful to incorporate two key caveats: (1) The level of uncertainty of the time frames, even if only scientific uncertainty is considered, and (2) the reliance of such estimates on adequate funding.

The first of these caveats is often elided, but it is simple: I estimate that we have a 50% chance of achieving the milestone of "robust human rejuvenation" (essentially, the rejuvenation of 60 year olds comprehensively enough that they won't be biologically 60 again until they're chronologically 90) within 25 years, but I also estimate that we have at least a 10% chance of not getting there in 100 years. But...that is all subject to the second caveat, namely funding.

Tragically, the level of funding that has been forthcoming during the past decade is only a few percent (at most) of what is necessary. The rate of progress in research to defeat aging has been quite amazing in view of that, but nonetheless, I estimate that it has been only about one-third of what could have been achieved with 10-20 times more money.

Which is much as I said yesterday: there are now plenty of researchers and research groups who would work on building real rejuvenation biotechnology as described in the SENS vision if they were given a budget to do so. That budget is, however, sadly lacking at this time. Millions of dollars are going to SENS and SENS-like research programs these days (which is a big improvement over their non-existence ten years ago) - but a hundred times that flow of resources would be needed to achieve earnest progress at the best possible rate.

One of the logical conclusions emerging from this point of view is that longevity science remains in that stage of growth wherein advocacy and education are the primary drivers of progress. There is sufficient buy-in from the scientific community to make institutional investment in research the bottleneck to progress, and obtaining that funding is a matter of persuasion.

In one sense this is encouraging: it is a characteristic state of affairs during a rapid shift in priorities for any field of human endeavor. Organizations with large sums to place into research tend to be the most conservative portions of their community, and thus among the last to heed the changing winds of knowledge and priority. This present stage, in which researchers are now interested and supportive but lacking in sources of funding that will allow them to actually work on the problem at hand, is a natural, albeit frustrating, part of the process. It is a considerable step up from the previous era in which few researchers had any interest in working on the biotechnologies of engineered human longevity, and even talking about it in public was discouraged.

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

Keeping up on the health basics makes a difference even in the last years of life: "It is well known that lifestyle factors, like being overweight, smoking and heavy drinking, predict death among elderly people. But is it uncertain whether these associations are applicable to people aged 75 years or more. So a team of researchers based in Sweden measured the differences in survival among adults aged 75 and older based on modifiable factors such as lifestyle behaviours, leisure activities, and social networks. The study involved just over 1,800 individuals who were followed for 18 years (1987-2005). Data on age, sex, occupation, education, lifestyle behaviours, social network and leisure activities were recorded. During the follow-up period 92% of participants died. Half of the participants lived longer than 90 years. Survivors were more likely to be women, be highly educated, have healthy lifestyle behaviours, have a better social network, and participate in more leisure activities than non-survivors. The results show that smokers died one year earlier than non-smokers. Former smokers had a similar pattern of survival to never smokers, suggesting that quitting smoking in middle age reduces the effect on mortality. Of the leisure activities, physical activity was most strongly associated with survival. The average age at death of participants who regularly swam, walked or did gymnastics was two years greater than those who did not. Overall, the average survival of people with a low risk profile (healthy lifestyle behaviours, participation in at least one leisure activity, and a rich or moderate social network) was 5.4 years longer than those with a high risk profile (unhealthy lifestyle behaviours, no participation in leisure activities, and a limited or poor social network). Even among those aged 85 years or older and people with chronic conditions, the average age at death was four years higher for those with a low risk profile compared with those with a high risk profile. In summary, the associations between leisure activity, not smoking, and increased survival still existed in those aged 75 years or more, with women's lives prolonged by five years and men's by six years, say the authors. These associations, although attenuated, were still present among people aged 85 or more and in those with chronic conditions."

Link: http://www.eurekalert.org/pub_releases/2012-08/bmj-hli082912.php

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

The cancer stem cell hypothesis continues to show promise as a way to strike at the root of many different forms of cancer: "Cancer stem cells are defined by three abilities: differentiation, self-renewal and their ability to seed a tumor. These stem cells resist chemotherapy and many researchers posit their role in relapse. A [new study] shows that melanoma cells with these abilities are marked by the enzyme ALDH, and imagines new therapies to target high-ALDH cells, potentially weeding the body of these most dangerous cancer creators. ... We've seen ALDH as a stem cell marker in other cancer types, but not in melanoma, and until now its function has been largely unknown. ... [Researchers] transplanted ALDH+ and ALDH- melanoma cells into animal models, showing the ALDH+ cells were much more powerfully tumorigenic. In the same ALDH+ cells, the group then silenced the gene that creates this protein, finding that with ALDH knocked down, melanoma cells died in cultures and lost their ability to form tumors in animal models. In cell cultures, silencing this ALDH gene also sensitized melanoma cells to existing chemotherapies. When the group explored human tumor samples, they found distinct subpopulations of these ALDH+ cells, which made up about 0.1-0.2 percent of patients' primary tumors. In samples of metastatic melanoma - the most aggressive form of the disease - the percentage of ALDH+ cells was greater, even over 10 percent in some tumors, further implying the powerful danger of these cells."

Link: http://www.coloradocancerblogs.org/news/study-identifies-human-melanoma-stem-cells

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

The public attitude towards cryonics has shifted greatly over the past ten years, at least as measured by the changing tenor of articles in the popular press. They are more favorable, more respectful, and more accurate on technical details. So greater exposure and publicity over the past decade has brought benefits, and increasing familiarity with the topic has allowed more people to overcome whatever knee-jerk reactions they normally have to all novel ideas. This is a positive trend, perhaps driven as much by the general proliferation of media enabled by the internet as by efforts made by the cryonics community, and will hopefully continue apace.

The Cryonic Man: How Alcor Life Extension preserves your dead body

What is it to die? For some, death is our body's expiration date, for others it is an absolute point where the soul leaves the body. For a group of scientists in Scottsdale, Arizona, however, it is merely an arbitrary natural accident, an engineering problem we have yet to find a solution for.

The Alcor Life Extension Foundation is the world's leading provider of cryonics, the practice of using ultra-cold temperatures to preserve humans until such a time when medicine is advanced enough to restore good health. The widely-held belief that it involves freezing is actually something of a red herring. As soon as possible after legal death is pronounced, cryoprotectant solution - a sort of antifreeze - is administered to a patient through their circulatory system, entering almost every cell in the body. Known as vitrification, this process avoids ice crystal formation and allows the body to be cooled with virtually no freezing damage, before being placed in liquid nitrogen in a Dewar container and moved to storage indefinitely.

For a long time cryonics was dismissed by many as science-fiction, an unnatural or even immoral procedure, but while the company make no bones about cryonics being an entirely speculative process, futurist and Alcor chief executive Max More says that the field is gaining legitimacy in the eyes of others. "People have certainly grown less hostile," he told Metro. "In terms of how science looks at cryonics we've definitely seen an improvement over time." Mr More added that Alcor's teams which intervene at members' deathbeds are also being treated more favourably by doctors. "Our relationship with hospitals and hospices has also improved; they used to be very adversarial and reluctant to even let us in, now hospital staff are usually fascinated and want to help in any way they can. They even let us position our equipment in the room next to the patient before clinical death, their whole attitude has really turned around."

Cryonics is an important industry, the only option for all too many people who will die before the advent of rejuvenation biotechnology. It has not found the level of growth that it deserves, sadly, but that doesn't change the fact that it is still the sole chance at a longer life in the future for those who are very old today.

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

Many different sources of stem cells remain under investigation, such as those derived from amniotic fluid: "We recently reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo). Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume [was] significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG) and the subventricular zone (SVZ) of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. ... This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22912905

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

Type 2 diabetes is a self-inflicted medical condition for the vast majority of sufferers. You get it by consistently eating too much and accumulating a large amount of visceral fat tissue, thereby suffering all of the unpleasant metabolic consequences that it brings. The more you do this, the greater your risk. The path to diabetes is a gradual increase in metabolic disarray that first passes through what is known as metabolic syndrome before becoming full blown diabetes. Some people are susceptible than others as a result of genetic differences, but the road is basically the same for everyone: eating yourself into sickness takes years of effort, but in a wealthy society nearly everyone has the resources to do it.

Here is the interesting thing: at almost any point along the way, right up until either morbid obesity or later stage diabetes, this can all be reversed. A person can step off the path of increasing disability and head back to a healthier lifestyle, turning back the progression of diabetes. This can even be accomplished in a fairly drastic way by enlisting calorie restriction:

An extreme eight-week diet of 600 calories a day can reverse Type 2 diabetes in people newly diagnosed with the disease .... the low-calorie diet reduced fat levels in the pancreas and liver, which helped insulin production return to normal. Seven out of 11 people studied were free of diabetes three months later.

Not that I'm suggesting that it's smart to eat gluttonously for half your life and then rely on having your fat pulled from the fire this way - there are other consequences to being overweight for an extended period of time, as shown by risk levels of suffering age-related diseases in later life. But here is another more recent study to illustrate the point that cutting back and changing lifestyle is very powerful when it comes to diabetes, as it restores some of the brain's activity with respect to food that becomes disarrayed in diabetics.

Short-Term Caloric Restriction Normalizes Hypothalamic Neuronal Responsiveness to Glucose Ingestion in Patients With Type 2 Diabetes:

The hypothalamus is critically involved in the regulation of feeding. Previous studies have shown that glucose ingestion inhibits hypothalamic neuronal activity. However, this was not observed in patients with type 2 diabetes. Restoring the energy balance by reduction of the caloric intake and weight loss are important therapeutic strategies in patients with type 2 diabetes. We hypothesized that caloric restriction would have beneficial effects on the hypothalamic neuronal response to glucose ingestion.

Functional magnetic resonance imaging was performed in 10 male type 2 diabetic patients before and after a 4-day very low calorie diet (VLCD) [to measure] neuronal activity in the hypothalamus in response to an oral glucose load.

...

Post-VLCD scans showed a prolonged signal decrease after glucose ingestion. The results of the current study demonstrate that short-term caloric restriction readily normalizes hypothalamic responsiveness to glucose ingestion in patients with type 2 diabetes.

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

I note that the Russian community behind the well-backed 2045 initiative are trying their hands at launching a political party to further the cause. There is a website for the Evolution 2045 party concept; at this point it would seem to be chiefly worthwhile as a way to gain some additional insight into the thinking of those steering the 2045 initiative:

The Initiative 2045 announces the creation of its own political party - "Evolution 2045" - in order to advocate for a new strategy for human development.
This is a Russia-based party, but its goals are international and global. Our ultimate goal is to inspire other countries to follow suit, and compete not in the arms race, but in the race for building a bright future for mankind.

There is a fair amount of money behind this project, so they can certainly afford the luxury of trying a great many different approaches in the course of gathering greater support for their cause. In this sense a nascent political party falls into exactly the same bucket as the series of international conferences being organized: outreach, education, advocacy.

This all seems to be an idea very much in the air at the Russian end of the longevity advocacy community. See this recent and unrelated item, for example:

we made the first step towards the creation of the Longevity Party. The initiative group of 10 people gathered together in Moscow to establish the first political party aimed at extending human lifespan using technological advances. ... . This is the very first step in the long and hard process of legally registering a political party. ... The next big thing we need to do is to finalize the Program of the Party. Then we have to have at least 2 people in 42 regions of Russia as representatives of the Party and have the founding meeting after which the Party can be registered and eventually appear in the voting ballots. Our goal is to influence the authorities to support life extension technologies and increase funding for research aimed at improving people's health and extending longevity.

Single issue political parties are a long-standing and widely used methodology for advancing particular causes in Europe and further East, far more so than across the pond in the US, though they do exist there as well. In most European countries you'll find a range of these organizations, some more successful than others. The Green parties are perhaps the exemplar of the type, formed around a movement and grown to staid success in terms of delivering their message, with the Pirate parties as another, younger and still dynamic example.

Either way, radical optimism about what can be achieved in the near future - if we just worked at it - is in comparatively short supply in our culture. Visionaries who talk about the path to humanity ascendant are a small minority in comparison to the masses and the talking heads who are blinkered by the present and look little further than the bounds of what is. So more vision and more optimism are very welcome, even if harnessed to a program that isn't my first choice for how to proceed towards engineering greatly extended lives.

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

Many research groups are working on building blood vessels. Here is one: scientists "have developed [an] artificial functioning blood vessel outside of the body, made from reprogrammed stem cells from human skin. The team also saw the cells develop into a blood vessel inside the body for the first time. The new technique could have real potential to treat patients with heart disease [by] either injecting the reprogrammed cells into the leg or heart to restore blood flow or grafting an artificially developed vessel into the body to replace blocked or damaged vessels. ... this new study demonstrates that a new type of partial stem cell developed from fibroblasts (skin cells) can be reprogrammed into vascular cells before going into the body, which have no risk turning into tumours. The [team] introduced four genes to human fibroblasts in the laboratory to reprogramme them into partial stem cells so they could become vascular cells. When these newly created cells were injected into an ischemic leg (a leg with restricted blood flow) in an animal model, the function of the leg was improved. The process of developing vascular cells from skin cells took two weeks, which makes a personalised approach of turning a patient's own skin cells into vascular cells feasible for treatment of vessel-blocking related diseases. The researchers say the next step is to test this approach in cells from patients with vascular disease."

Link: http://www.kcl.ac.uk/newsevents/news/newsrecords/2012/08-Aug/pioneering-heart-disease-treatment.aspx

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

Other than calorie restriction, regular exercise is the most potent presently available method available to maintain health and extend life expectancy - which is actually more of a criticism of our lack of advanced biotechnology than praise for the merits of exercise. Exercise is beneficial even for the elderly, however, and one part of the downward spiral that comes with age is that loss of strength and increasing frailty constrain the ability to exercise sufficiently vigorously to obtain its benefits. This is true even for the longest-lived humans: "Ageing is a continuum of biological processes characterized by progressive adaptations which can be influenced by both genetic and physiological factors. In terms of human maturation, physically and cognitively functional centenarians certainly represent an impressive example of successful healthy ageing. However, even in these unique individuals, with the passage of time, declining lung function and sarcopenia lead to a progressive fall in maximal strength, maximal oxygen uptake, and therefore reduced exercise capacity. The subsequent mobility limitation can initiate a viscous downward spiral of reduced physical function and health. Emerging literature has shed some light on this multi-factorial decline in function associated with aging and the positive role that exercise and physical capacity can play in the elderly. Recognizing the multiple factors that influence ageing, the aim of this review is to highlight the recently elucidated limitations to physical function of the extremely old and therefore evaluate the role of exercise capacity in the health and longevity of centenarians."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22883374

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

The immune system is vital for many reasons. It is not just a barrier against pathogens of all sorts, such as bacteria, fungi, and viruses, but also a watchdog that hunts down and destroys harmful cells, such as those that have entered senescence or are in danger of becoming cancerous. In later life the immune system declines and fails in characteristic ways, partly a consequence of its evolved structure and resource limits, and partly the same general accumulation of damage that affects all cells in the body. The failure of the immune system is important because it contributes to other threads in aging: allowing senescent cells to build up, failing to catch cancers when they can be easily destroyed, and generating ever higher levels of inflammation. This increasing incapacity alongside increasing inflammation is known as immunosenescence or inflammaging.

Here is an open access paper on the subject:

Hallmarks of human "immunosenescence": adaptation or dysregulation?

Is immunosenescence an intrinsic ageing process leading to dysregulation of immunity or an adaptive response of the individual to pathogen exposure? Age-associated differences in bone marrow immune cell output and thymic involution suggest the former. Accepted hallmarks of immunosenescence (decreased numbers and percentages of peripheral naïve T cells, especially CD8+?cells, and accumulations of memory T cells, especially late-stage differentiated CD8+ cells) suggest the latter, viewed as the result of depletion of the reservoir of naïve cells over time by contact with pathogens and their conversion to memory cells, the basis of adaptive immunity.

Thymic involution beginning early in life limits the generation of naive cells such that the adult is believed to rely to a great extent on the naïve cell pool produced mostly before puberty. Thus, these hallmarks of immunosenescence would be markedly affected by the history of the individual's exposure to pathogens, [and] in humans, particularly to infection with CMV.

...

One very striking difference [between industrialized Western populations and those of poorer regions is that in] the "wild-type" situation, all humans are infected with CMV from the age of ca. 2?months on, when they no longer receive only anti-CMV antibody in the mother's milk, but also the infectious virus that has reactivated in the meantime. CMV-negativity is an artifact of civilization, hygiene and decreased breast feeding. Hence, in our pilot study of young and old men in rural Pakistan, all the young were already CMV-positive. As "old" is viewed as [greater than] 50?years in this society, we sought to establish whether age-associated differences in immune phenotypes that we and others had established in older European and US populations were similar in Pakistanis, and whether they manifested earlier in the latter.

We concluded that there were two major differences between the Pakistani population and the historical controls of [subjects from Western, industrialized regions]. One was that we did indeed see age-associated differences in CD8+ T cells earlier in the Pakistanis, and the other was that we saw for the first time in a healthy population that not only the CD8+ subset but also the CD4?+?T cells were affected. This we had otherwise only seen in pathological European populations, eg. those with Alzheimer's. We interpret this to mean that the level of "antigenic stress" in the Pakistani population, old at 50, could indeed be leading to "premature immunosenescence".

Some thoughts on what can be done to reverse some of the declines in the aging immune system - alongside a few concrete results in laboratory animals - can be found a little way back in the Fight Aging! archives.

• Prospects for Immune System Rejuvenation Through Selective Destruction
• Immune System Rejuvenation Achieved Through Targeted Cell Destruction
• Exercise and the Destruction of Age-Damaged Immune Cells

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

Another branch of targeted therapies is the design of nanofactories that can be steered to specific locations in the body and there produce proteins and other drugs in response to local conditions or external commands. Early work in this field is underway: "Science is one step closer to producing drugs in the right place at the right time in the body, avoiding the collateral damage of untargeted treatments. Researchers [have] designed nanoparticles that can be stimulated via UV light to produce proteins on demand in vivo. The new method, which involves packaging the molecular machinery for making proteins into a membraned capsule, allows the researchers to spatially and temporally regulate protein production ... The scientists created the nano-sized 'protein factories' by using lipids to encapsulate polymerase and other machinery necessary for protein production from E. coli, along with a DNA plasmid containing a gene of interest. To block transcription until the right moment, they added a DNA 'photo-labile cage' to the plasmid - a small chemical that inhibits transcription but is cleaved by exposure to UV light. To test the principle in vivo, the researchers used luciferase as the reporter protein and injected mice with the nanovesicles. After zapping them with UV light at the site of injection, they were able to measure a local burst of luminescence. ... We have a long way to go still before we have a drug factory that will land in a target tissue to produce a drug of interest ... The study has proved the principle of the first step - getting the protein expressed on signal - but future research will need to ensure that the nanoparticles and the proteins they produce aren't toxic in the wrong place, and that they get to the right location. Targeting the nanoparticles to the appropriate tissues might be achieved by 'decorating' the surface of the vesicles with specific proteins."

Link: http://the-scientist.com/2012/08/13/next-generation-in-vivo-drug-factories/

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