Telomere Length Alone is Not a Good Biomarker of Aging

Different people age at different rates. Efforts have long been underway to find a reliable, effective way to measure physiological age in order to relate that to remaining life expectancy and mortality rate. Without a biomarker of aging that can be easily measured, it will remain very challenging to evaluate future therapies that intervene in the aging process: how do you know whether a particular medical technology worked, or whether it worked better or worse than a competing therapy?

The wait and see approach for determining effects on life span requires years and millions of dollars in mouse studies, while finding a definitive answer in humans is out of the question on the time scales involved here. The whole field of medicine will be transformed over the next two decades, but it would take much longer than that to even begin to answer simple questions as to effects of prospective rejuvenation therapies in humans.

Telomeres are protective caps at the end of chromosomes. Their length is determined by a number of dynamic lengthening and shortening processes, but on average tends to erode with age or ill health. Thus telomere length has been proposed as a biomarker of aging, but as this paper shows simple measures of average telomere length are not all that useful in and of themselves:

The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure.

Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites.

Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

In this context, you may want to look at another recent paper where the authors suggest that more sophisticated measures of telomere dynamics, such as counting changes in the proportion of very short telomeres, are in fact good biomarkers of aging.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23028820

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