Protein Shown to Be Natural Inhibitor of Aging in Fruit Fly Model

[steven johnson]

It looks as though they have found the biochemical mechanism by which caloric restriction can lengthen life span in fruit flies. If it applies to humans, it might be a mechanism to activate to prolong human life.

If not, we can still have as many geriatric fruit flies as we want buzzing around our bananas.

Scientists at the University of California, San Diego School of Medicine, have identified a protein called Sestrin that serves as a natural inhibitor of aging and age-related pathologies in fruit flies. They also showed that Sestrin, whose structure and biochemical function are conserved between flies and humans, is needed for regulation of a signaling pathway that is the central controller of aging and metabolism.

Sestrins are highly conserved small proteins that are produced in high amounts when cells experience stress. Sestrin function, however, remained puzzling until the Karin group found that these proteins function as activators of AMP-dependent protein kinase (AMPK), and inhibitors of the Target of Rapamycin (TOR). AMPK and TOR are two protein kinases that serve as key components of a signaling pathway shown to be the central regulator of aging and metabolism in a variety of model organisms, including the worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and mammals.

AMPK is activated in response to caloric restriction, a condition that slows down aging, whereas TOR is activated in response to over-nutrition, a condition that accelerates aging. Activation of AMPK inhibits TOR, and drugs that activate AMPK or inhibit TOR can delay aging in several different model organisms including mammals. But how the body keeps the activity of these two protein kinases in balance to prevent premature aging was unknown. Additionally, the presence of three different genes encoding Sestrins in mammals made it difficult to identify their exact physiological function in live animals.

The new study took advantage of the finding that the fruit fly Drosophila, whose AMPK-TOR signaling pathway functions in the same manner as its mammalian equivalent, contains a single Sestrin gene... "Strikingly, the pathologies caused by the Sestrin deficiency included accumulation of triglycerides, cardiac arrhythmia and muscle degeneration that occurred in rather young flies," said Karin. "These pathologies are amazingly similar to the major disorders of overweight, heart failure and muscle loss that accompany aging in humans."


Protein Shown to Be Natural Inhibitor of Aging in Fruit Fly Model