A Possible Metabolic Signature of Biological Age in Mice

A low-cost, reliable method of measuring biological age is greatly sought after by the research community. People and laboratory animals age at different rates - by which I mean that they accumulate damage and changes characteristic of aging at different rates. Thus two individuals of the same species and same chronological age might have different biological ages thanks to life style, environment, access to medicine, and so forth.

Some interventions, such as calorie restriction, can slow the pace at which an individual ages, but measuring this slowing is a challenging process. Biological age is a simple concept at the high level, but finding a quick and reliable way to actually measure it has yet to happen. Thus while researchers would like to have rapid answers as to how effective any given method of slowing aging might be, they must wait and run long-lasting studies. The bottom line measure for any slowing of aging is to wait for the individuals in question to live out their lives and thus measure by effect on life span. Even in short-lived mice this can require years and thus a great deal of money. In longer-lived animals, ourselves included, it is simply impractical to run the necessary studies.

When it comes to the forthcoming generation of therapies capable of limited rejuvenation - by repairing some of the damage that causes degenerative aging - the situation is much the same, as is the need for a quick and easy measure of biological age. A therapy that actually produces some degree of rejuvenation should make a laboratory animal biologically younger than peers with the same chronological age. But how to measure that change without employing the lengthy and expensive wait-and-see approach?

Given the present state of affairs, any quick measure of biological age will speed research, making it very much faster and cheaper to assess varied means of extending healthy life. Some experiments that would presently require a year or more could be conducted in a few weeks or months: apply the therapy and evaluate the resulting changes in measures of biological age.

Several lines of research look promising when it comes to yielding a way to reliably and consistently evaluate biological age. One involves measurement of DNA methylation levels, and despite initial setbacks it may yet prove possible to tease out a useful measure from changes in the dynamics of telomere length. There are others. Here, for example, is a recent paper in which researchers present a method based on measurement of metabolite levels:

A metabolic signature predicts biological age in mice

Our understanding of the mechanisms by which aging is produced is still very limited. Here, we have determined the sera metabolite profile of 117 wild-type mice of different genetic backgrounds ranging from 8-129 weeks of age. This has allowed us to define a robust metabolomic signature and a derived metabolomic score that reliably/accurately predicts the age of wild-type mice.

In the case of telomerase-deficient mice, which have a shortened lifespan, their metabolomic score predicts older ages than expected. Conversely, in the case of mice that over-express telomerase, their metabolic score corresponded to younger ages than expected.

Importantly, telomerase reactivation late in life by using a TERT based gene therapy recently described by us, significantly reverted the metabolic profile of old mice to that of younger mice ... These results indicate that the metabolomic signature is associated to the biological age rather than to the chronological age. This constitutes one of the first aging-associated metabolomic signatures in a mammalian organism.

This might turn out to be an indirect measure of telomerase activity and little else, as over-specific matching is always a potential issue when searching for patterns in a large and complex system such as mammalian metabolism. Testing this metabolic signature against other means of accelerating or slowing aging in mice - such as calorie restriction - is thus one obvious next step.


The other paper (cited above) by some of the same authors -
"Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice"
- indicates that telomerase reactivation does rejuvenate some tissues and extends median lifespan, in cancer-resistant mice.

Another paper - finds a significant positive correlation between short telomeres and longevity, body size and stress resistance - probably an anti-cancer strategy.

Posted by: Lou Pagnucco at November 2nd, 2012 10:34 PM
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