When it comes to medical procedures, everyone has their own definition of acceptable risk. Sadly we&re then overruled by faceless bureaucrats at the US Food and Drug Administration (FDA) and similar government bodies & people who have only their own interests in mind, and suffer no consequences from making useful medical technologies illegal or too expensive for commercial use. Fortunately, the FDA doesn&t rule the world: there are regions in which medical regulations are less onerous and therapies less costly, and these locations are only a plane flight away.

People who undertake medical tourism for stem cell therapies are demonstrating their own risk preferences: balancing the plausible expected benefits based on what is presently known of the science and the outcomes (in the absence of rigorous trials) against the cost and estimated risk. For stem cell treatments perhaps the largest inherent risk for early stage therapies is that of cancer resulting from the activities of transplanted cells. Work in the laboratory suggests that this risk is generally lower than first thought, but it still exists.

The world of cancer treatments is, meanwhile, changing profoundly, gearing up for a new generation of therapies that will displace chemotherapy and radiotherapy. Reprogramming immune cells or introducing targeted viruses and nanoparticles to seek out and kill cancer cells with few side-effects will be the standard operating procedure twenty years from now & and probably available outside the US in a decade. In early trials and the laboratory, these technologies are already showing impressive results.

Improvements in cancer treatment & leading to the introduction of robust therapies that can clear most common forms of cancer quickly and without accompanying illness & will, I think, go hand in hand with a far greater demand for and use of very aggressive stem cell treatments. Things like periodic infusions of massive numbers of immune cells cloned from a patient&s own cells, done not just for people with medical conditions, but for the healthy as a beneficial preventative measure. Similarly, why boost regeneration and tissue maintenance via stem cell therapies only in the sick and the wounded? That makes sense if there is a significant risk associated with treatment, but in a world in which cancer is merely troublesome, why not make stem cell therapies a part of general health maintenance?

These are the sort of shifts in the cost-benefit picture of regenerative medicine that will emerge over the next couple of decades, driven by a growing ability to control the undesirable aspects of cellular biology, such as cancer.

Source:
http://www.fightaging.org/archives/2013/04/robust-cancer-therapies-will-mean-a-greater-use-of-aggressive-stem-cell-therapies.php

Source:
http://www.longevitymedicine.tv/robust-cancer-therapies-will-mean-a-greater-use-of-aggressive-stem-cell-therapies/

Researchers here examine the published literature on hormesis via heat shock, one of the ways shown to induce modest gains in longevity in laboratory animals, and find less support for positive outcomes than was thought. This may or may not be significant & the goal for researchers, as for calorie restriction and other means of extending longevity, is to find the underlying mechanism of action and build a therapy that triggers it with minimal side-effects. So long as heat shock can be demonstrated to improve long term health and longevity under at least some conditions, then there is a mechanism to be found and exploited.

Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies.

Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23570942

Source:
http://www.fightaging.org/archives/2013/04/limited-evidence-for-the-universality-of-heat-shock-hormesis-as-a-way-to-induce-longevity.php

Source:
http://www.longevitymedicine.tv/limited-evidence-for-the-universality-of-heat-shock-hormesis-as-a-way-to-induce-longevity/

The clam species Arctica islandica is very long-lived, reaching at least four centuries in the wild. Researchers are comparing its biochemistry with similar but shorter-lived species to see if they can pinpoint the mechanisms that lead to its exceptional longevity. Here is recent research on this topic:

The observation of an inverse relationship between lifespan and mitochondrial H2 O2 production rate would represent strong evidence for the disputed oxidative stress theory of aging. Studies on this subject using invertebrates are surprisingly lacking, despite their significance in both taxonomic richness and biomass. Bivalve molluscs represent an interesting taxonomic group to challenge this relationship. They are exposed to environmental constraints such as microbial H2 S, anoxia/reoxygenation, and temperature variations known to elicit oxidative stress. Their mitochondrial electron transport system is also connected to an alternative oxidase that might improve their ability to modulate [the reactive oxygen species (ROS) generated by mitochondria and which produce oxidative stress].

Here we compared H2 O2 production rates in isolated mantle mitochondria between the longest living metazoan & the bivalve Arctica islandica & and two taxonomically related species of comparable size. In an attempt to test mechanisms previously proposed to account for a reduction of ROS production in long-lived species, we compared oxygen consumption of isolated mitochondria and enzymatic activity of different complexes of the electron transport system in the two species with the greatest difference in longevity.

We found that A. islandica mitochondria produced significantly less [of the reactive oxygen species] H2 O2 than those of the two short-lived species in nearly all conditions of mitochondrial respiration tested, including forward, reverse, and convergent electron flow. Alternative oxidase activity does not seem to explain these differences. However, our data suggest that reduced complex I and III activity can contribute to the lower ROS production of A. islandica mitochondria, in accordance with previous studies.

Reduced activity within mitochondria in this sense shows up in some longevity-inducing mutations in laboratory animals. Mitochondrial activity and composition (how much damage they cause per unit time, and how resistant they are to damage) appears to be very important as a determinant of longevity differences between species. This should increase our interest in ways to repair mitochondrial damage in humans as a potential rejuvenation therapy.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23566066

Source:
http://www.fightaging.org/archives/2013/04/examining-the-biochemistry-of-arctica-islandica-longevity.php

Source:
http://www.longevitymedicine.tv/examining-the-biochemistry-of-arctica-islandica-longevity/

A fair number of research groups worldwide are gathering and processing data in search of associations between minor genetic variations and human longevity. As for all studies of long-term human health, this a challenging process: statistics become involved, it is costly to gather data of even moderate quality, and the underlying biology is exceedingly complex. This is illustrated by the fact that comparatively few genetic associations can be validated across different study populations: if you find a genetic polymorphism with a statistically significant association with longevity in Italian lineages, the odds are very good that it won&t show up in Asian populations, or even in other Italian study populations, for that matter. The range of minor variation in the human genome is very large, and it seems to be the case that there are many, many tiny genetic contributions to the way in which metabolism interacts with environment to determine natural longevity, most of which differ widely in different populations.

So while the funding lasts, this is a deep well for researchers to work on & just not one likely to produce more than knowledge for the foreseeable future. If you want actual results in terms of therapies to reverse the course of aging, then look to the programs described in the SENS research outline. The research community already knows what needs to be repaired in aged tissue, as the low-level differences between old and young tissue are well enumerated & it is the intricate, enormously complex metabolic dance of progressing from undamaged to damaged that remains an open field of work. The difference between SENS and the mainstream efforts to fully understand aging is the difference between on the one hand making the effort to rust-proof a metal surface and on the other producing a complete and detailed model of how rust progresses and interacts with metal structures at every level, from chemistry through to the physics of forces acting on structures and material strengths. The latter isn&t necessary to achieve the goal of prevention once you know what rust is, and indeed will probably prove to cost far more than just preventing the rust.

Here are a couple of illustrative papers from the steady flow of new associative studies of genetics and aging in humans. There will be many more similar results arriving in the years ahead: a lot more money goes towards this sort of work than to any effort to do something about aging.

The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy

Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence. TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL). The association of TERT SNPs with longevity remains uncertain and varies with ethnicity. Aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity.

MNS16A genotypes have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes. MNS16A appears associated to longevity. The MNS16A*L allele is significantly underrepresented in Age Class 3 compared to Age Class 2. The concomitant significant telomere cross sectional attrition rate observed for L*/L* genotype suggests that this polymorphism could influences human longevity by affecting TL.

Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans

Nitric oxide (NO) triggers multiple signal transduction pathways and contributes to the control of numerous cellular functions. Previous studies have shown in model organisms that the alteration of NO production has important effects on aging and lifespan. We studied in a large sample (763 subjects, age range 19-107 years) the variability of the three human genes (NOS1, -2, -3) coding for the three isoforms of the NADPH-dependent enzymes named NO synthases (NOS) which are responsible of NO synthesis.

We found that gene variation of NOS1 and NOS2 was associated with longevity. In addition NOS1 rs1879417 was also found to be associated with a lower cognitive performance, while NOS2 rs2297518 polymorphism showed to be associated with physical performance. Moreover, SNPs in the NOS1 and NOS3 genes were respectively associated with the presence of depression symptoms and disability, two of the main factors affecting quality of life in older individuals. On the whole, our study shows that genetic variability of NOS genes has an effect on common age related phenotypes and longevity in humans as well as previously reported for model organisms.

Source:
http://www.fightaging.org/archives/2013/04/examples-of-genetic-association-studies-of-human-longevity.php

Source:
http://www.longevitymedicine.tv/examples-of-genetic-association-studies-of-human-longevity/

Here is a popular science article on intermittent fasting, something that extends life in mice, but which is not as well researched as calorie restriction, the gold standard for science on healthy life extension. There appears to be considerable overlap in the mechanisms involved in calorie restriction and intermittent fasting, but it&s not all exactly the same when gene expression patterns are examined, to pick one example.

Many diet and exercise trends have origins in legitimate science, though the facts tend to get distorted by the time they achieve mainstream popularity. Benefits are exaggerated. Risks are downplayed. Science takes a backseat to marketing. One needn&t look any further than the emerging trend of intermittent fasting for a prime example.

There is indeed a large body of research to support the health benefits of fasting, though most of it has been conducted on animals, not humans. Still, the results have been promising. Fasting has been shown to improve biomarkers of disease, reduce oxidative stress and preserve learning and memory functioning. [There] are several theories about why fasting provides physiological benefits. &The one that we&ve studied a lot, and designed experiments to test, is the hypothesis that during the fasting period, cells are under a mild stress. And they respond to the stress adaptively by enhancing their ability to cope with stress and, maybe, to resist disease.&

But perhaps it isn&t so much the fasting that produces health benefits, per se, as the resulting overall reduction in calorie intake (if, that is, you don&t overeat on nonfasting days, which could create a caloric surplus instead of a deficit). That appears, at least, to be the case in slowing diseases such as cancer in mice. &Caloric restriction, undernutrition without malnutrition, is the only experimental approach consistently shown to prolong survival in animal models,& In [a] study, mice fasted twice a week for 24 hours, but were otherwise permitted to eat at liberty. During nonfasting days, the mice overate. Overall, they did not lose weight, counteracting whatever benefits they might have seen from fasting. Intermittent fasting with compensatory overeating &did not improve mouse survival nor did it delay prostrate tumor growth,& the study concluded.

Equally, there are studies showing that intermittent fasting without calorie restriction does extend life in nematode worms. A lot more research is needed to bring intermittent fasting up to the level of confidence that we can have in calorie restriction.

Link: http://www.cmaj.ca/site/earlyreleases/8apr13_intermittent-fasting-the-science-of-going-without.xhtml

Source:
http://www.fightaging.org/archives/2013/04/on-intermittent-fasting-2.php

Source:
http://www.longevitymedicine.tv/on-intermittent-fasting/