Signaling Networks Determining Life Span

Annu Rev Biochem. 2016 Jun 2;85:35-64. doi: 10.1146/annurev-biochem-060815-014451.

Abstract

The health of an organism is orchestrated by a multitude of molecular and biochemical networks responsible for ensuring homeostasis within cells and tissues. However, upon aging, a progressive failure in the maintenance of this homeostatic balance occurs in response to a variety of endogenous and environmental stresses, allowing the accumulation of damage, the physiological decline of individual tissues, and susceptibility to diseases. What are the molecular and cellular signaling events that control the aging process and how can this knowledge help design therapeutic strategies to combat age-associated diseases? Here we provide a comprehensive overview of the evolutionarily conserved biological processes that alter the rate of aging and discuss their link to disease prevention and the extension of healthy life span.

Keywords: DNA damage; epigenetic regulation; inflammation; insulin-like signaling; mammalian aging; mitochondrial health; nutrient sensing; oxidative stress; proteostasis; telomere shortening.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Caloric Restriction
  • DNA Damage*
  • Epigenesis, Genetic
  • Homeostasis / genetics
  • Humans
  • Inflammation
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Longevity / genetics*
  • Mitochondria / metabolism
  • Oxidative Stress
  • Proteostasis Deficiencies / genetics*
  • Proteostasis Deficiencies / metabolism
  • Proteostasis Deficiencies / pathology
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Telomere Shortening*

Substances

  • Insulin-Like Growth Factor I
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases