Wednesday, November 18, 2009

PNAS Study on Telomere Length and Centenarians

Why is it that some people, who are exceptional cases, can live 100 years of disease-free life while the vast majority of their contemporaries die from cancer, heart disease or stroke 20-30 years earlier?

This is perhaps the most important question which the medical sciences should be tackling today, rather than the questions which currently dominant the "disease model" approach to health extension (e.g. what causes specific diseases, like cancer, stroke, AD, etc.).

If we had a better understanding of the things that influence "healthy aging" then we could reduce the increasing risks of morbidity and mortality which aging populations face.

Contrary to what most people might be inclined to think, exercise alone will not make the goal of a century of healthy life a reality for the vast majority of people alive today. If we are to increase the average life expectancy beyond 85 years, and do so in a way that "adds life to years, not simply years to life", we will need to find a way of modulating the aging process.

Studies like this one, published on the "Early View" of the Proceedings of the National Academy of Sciences, are where the real action is in terms of the new frontiers of the medical sciences. Here is the abstract:

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.

And an excerpt from the article:

In summary, we provide strong correlative evidence that individuals in Ashkenazi Jewish families with exceptional longevity have better maintenance of telomere length and that the telomerase genes may function as important genetic determinants of both human longevity and telomere length. Additionally, our data suggest that both telomere length and variants of telomerase genes may have a cumulative influence on lower disease prevalence and a favorable lipid profile in centenarians and their offspring. Additional comprehensive studies on genetic and genomic variation of centenarians and their offspring comprising candidate genes, especially those known to play a role in telomere maintenance in model organisms, may reveal previously undescribed genomic regions and molecules that are operative in human health and longevity.