Here, researchers identify another piece of the molecular machineries of metabolism that help to determine life span: "a protein called Sestrin [serves] as a natural inhibitor of aging and age-related pathologies in fruit flies. ... Sestrins are highly conserved small proteins that are produced in high amounts when cells experience stress. Sestrin function, however, remained puzzling until [researchers] 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. ... 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. ... In future work, [researchers plan] to examine whether the mammalian Sestrins also control aging and metabolism, and whether defects in proper Sestrin expression will provide the explanation to some of the currently unexplainable degenerative diseases associated with old age."