Sestrins orchestrate cellular metabolism to attenuate aging.
The Sestrins constitute a family of evolutionarily conserved stress-inducible proteins that suppress oxidative stress and regulate AMP-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis. Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction, and muscle degeneration, that resemble accelerated tissue aging. Likewise, Sestrin deficiencies in mice led to accelerated diabetic progression upon obesity. Further investigation of Sestrin function and regulation should provide new insights into age-associated metabolic diseases, such as diabetes, myopathies, and cancer.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Jun Hee
JH
Lee
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Andrei V
AV
Budanov
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology University of California, San Diego, San Diego, CA 92093, USA.
Michael
M
Karin
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging; D000818:Animals; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D009687:Nuclear Proteins; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases