Key proteins and pathways that regulate lifespan

J Biol Chem. 2017 Apr 21;292(16):6452-6460. doi: 10.1074/jbc.R116.771915. Epub 2017 Mar 6.

Abstract

Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway, and the mechanistic target of rapamycin (mTOR). Using insights derived from simple model organisms, mice, and humans we discuss how these proteins and pathways may potentially alter the rate of aging. We further describe how knowledge of these pathways may lead to the rational design of small molecules that modulate aging and hence alter the propensity for a host of age-related diseases.

Keywords: IGF-1; aging; insulin-like growth factor (IGF); lifespan; mammalian target of rapamycin (mTOR); mouse genetics; sirtuin; sirtuins.

Publication types

  • Review

MeSH terms

  • Aging*
  • Animals
  • Caenorhabditis elegans
  • Caloric Restriction
  • Gene Expression Regulation*
  • Humans
  • Insulin / physiology
  • Insulin-Like Growth Factor I / physiology*
  • Longevity*
  • Mice
  • Phosphorylation
  • Signal Transduction
  • Sirtuins / physiology*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Insulin
  • Insulin-Like Growth Factor I
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirtuins