Forever young?

One of my colleagues focuses much of his research interest on the biochemical control of the aging process. I wish he would work a little faster.

The cover story of this week's Science details the work of a group of scientists at UCSD's School of Medicine in which they have identified a protein that may play a major role in the inhibition of aging in fruit flies. The protein, known as sestrin, is also found in humans and seems to have a similar biochemical function. Sestrins have been known for some time, and are produced in abundance by cells under stress. Their function, however, had remained a mystery. The UCSD group demonstrates that sestrins serve to activate of AMP-dependent protein kinase (AMPK), and inhibit the Target of Rapamycin (TOR). These two protein kinases play a major role in the pathway that regulates the aging process in a wide range of organisms including the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and, yes, you.

The two kinases have opposite actions - AMPK is activated by a lowering of caloric intake, while increased intake activates TOR. It's been shown that drugs that stimulate AMPK or inhibit TOR can slow down aging in model organisms. Our understanding of sestrin function has been impeded by the fact that there are three different sestrin-encoding genes in mammals. In fruit flies, however, a single gene codes for the protein. When the researchers inactivated this gene, they saw decreased activity of AMPK and increased activity of TOR. The result was the development of a number of age-related pathologies.

The potential significance is huge - the researchers hope that sestrin or analogues may eventually be used to slow down the aging process and treat many of the degenerative diseases associated with aging. Good luck on that. Wish they had found this thirty years ago.