Editors' ChoiceAging

Sestrin and the Consequences of Aging

Science Signaling  09 Mar 2010:
Vol. 3, Issue 112, pp. ec75
DOI: 10.1126/scisignal.3112ec75

The protein kinase TOR (target of rapamycin) plays key roles in the control of fundamental biological processes, including growth, metabolism, aging, and immune function. Sestrin proteins show increased abundance in response to stress and have been implicated in control of TOR activity. Lee et al. (see the Perspective by Topisirovic and Sonenberg) characterized Drosophila fruit flies lacking sestrins. Sestrins were implicated in a negative feedback loop in which the abundance of sestrins is controlled by TOR activity, with sestrins concomitantly also inhibiting activity of TOR. Furthermore, flies lacking sestrins showed accumulation of fat, muscle degeneration, and heart abnormalities similar to those that plague aging humans with a sedentary life-style.

J. H. Lee, A. V. Budanov, E. J. Park, R. Birse, T. E. Kim, G. A. Perkins, K. Ocorr, M. H. Ellisman, R. Bodmer, E. Bier, M. Karin, Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327, 1223–1228 (2010). [Abstract] [Full Text]

I. Topisirovic, N. Sonenberg, Burn out or fade away? Science 327, 1210–1211 (2010). [Summary] [Full Text]