Biochemical Basis of Sestrin Physiological Activities

Trends Biochem Sci. 2016 Jul;41(7):621-632. doi: 10.1016/j.tibs.2016.04.005. Epub 2016 May 10.


Excessive accumulation of reactive oxygen species (ROS) and chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are well-characterized promoters of aging and age-associated degenerative pathologies. Sestrins, a family of highly conserved stress-inducible proteins, are important negative regulators of both ROS and mTORC1 signaling pathways; however, the mechanistic basis of how Sestrins suppress these pathways remains elusive. In the past couple of years, breakthrough discoveries about Sestrin signaling and its molecular nature have markedly increased our biochemical understanding of Sestrin function. These discoveries have also uncovered new potential therapeutic strategies that may eventually enable us to attenuate aging and age-associated diseases.

Keywords: ROS; Sestrin; aging; leucine; mTOR; structure.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemical Phenomena
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*


  • Heat-Shock Proteins
  • Nuclear Proteins
  • SESN1 protein, human
  • SESN2 protein, human
  • SESN3 protein, human