Thursday, July 16, 2009

Nature Study on Rapamycin and Lifespan of Mice

The most exciting and important field of science today is aging research. Understanding why we age- and become vulnerable to all the diseases that accompany aging (like cancer, heart disease, arthritis, AD, stroke, etc.)- could lead to the development of a drug that retards aging. Thus providing humans with the opportunity to enjoy better health in late life (and more years of health) by delaying the chronic diseases of aging.

The latest issue of Nature has this exciting study about the molecule rapamycin [first discovered in soil samples on Easter Island, hence the picture] which had previously been shown to extended the lifespan of invertebrates. But what about mammals? This new study shows it also extends the lifespan of mice. Here is the abstract:

Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies1; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.

And a small sample from the article:

Because incidences of most diseases rise rapidly with age, interventions that delay ageing would greatly benefit health. So far, dietary additives that delay ageing and increase lifespan in rodent models have shown only weak effects. Before clinical studies are considered, anti-ageing interventions must be repeatable and effective in many mouse genotypes, and not merely postpone strain-specific diseases.

....It is especially noteworthy that rapamycin feeding can extend mouse lifespan even when started late in life; in terms of the percentage of the maximal lifespan, a 600-day-old mouse is roughly the equivalent of a 60-year-old person14. An effective anti-ageing intervention that could be initiated later than the midpoint of the lifespan could prove to be especially relevant to clinical situations, in which the efficacy of anti-ageing interventions would be particularly difficult to test in younger volunteers. Our data justify special attention to the role of the TOR pathway in control of ageing in mammals and in the pathogenesis of late-life illnesses.

And there is also a News and Views feature on the study here. A sample:

The small molecule rapamycin, already approved for clinical use for various human disorders, has been found to significantly increase lifespan in mice. Is this a step towards an anti-ageing drug for people?

Anti-ageing drugs — compounds that slow the hands of time and allow humans to live far beyond their natural span — have long been fertile ground for science-fiction writers. More recently, however, the possibility that such compounds might exist, and might perhaps even be within reach, has gained scientific credibility. In this issue (page 392), Harrison et al.1 provide evidence that pharmacological intervention in the ageing process is feasible in mammals. They report that dietary supplementation with rapamycin — a compound known to be linked to lifespan in invertebrates — significantly increases the lifespan of mice.

....Is this the first step towards an anti-ageing drug for people? Certainly, healthy individuals should not consider taking rapamycin to slow ageing — the potential immunosuppressive effects of this compound alone are sufficient to caution against this. On the basis of animal models, however, it is interesting to consider that rapamycin — or more sophisticated strategies to inhibit TOR signalling — might prove useful in combating many age-associated disorders. Also, as relevant downstream targets of TOR are better characterized, it may be possible to develop pharmacological strategies that provide the health and longevity benefits without unwanted side effects. So, although extending human lifespan with a pill remains the purview of science-fiction writers for now, the results of Harrison et al. provide a reason for optimism that, even during middle age, there's still time to change the road you're on.