Cellular senescence and the aging brain

Exp Gerontol. 2015 Aug;68:3-7. doi: 10.1016/j.exger.2014.09.018. Epub 2014 Oct 1.

Abstract

Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies.

Keywords: Aging; Brain; Cellular senescence; Neurodegeneration; Senescence associated secretory phenotype.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / cytology
  • Brain / physiology*
  • Cell Proliferation / physiology
  • Cellular Senescence / physiology*
  • Humans
  • Mice
  • Models, Neurological
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology