Senescence and apoptosis: dueling or complementary cell fates?

EMBO Rep. 2014 Nov;15(11):1139-53. doi: 10.15252/embr.201439245. Epub 2014 Oct 13.

Abstract

In response to a variety of stresses, mammalian cells undergo a persistent proliferative arrest known as cellular senescence. Many senescence-inducing stressors are potentially oncogenic, strengthening the notion that senescence evolved alongside apoptosis to suppress tumorigenesis. In contrast to apoptosis, senescent cells are stably viable and have the potential to influence neighboring cells through secreted soluble factors, which are collectively known as the senescence-associated secretory phenotype (SASP). However, the SASP has been associated with structural and functional tissue and organ deterioration and may even have tumor-promoting effects, raising the interesting evolutionary question of why apoptosis failed to outcompete senescence as a superior cell fate option. Here, we discuss the advantages that the senescence program may have over apoptosis as a tumor protective mechanism, as well as non-neoplastic functions that may have contributed to its evolution. We also review emerging evidence for the idea that senescent cells are present transiently early in life and are largely beneficial for development, regeneration and homeostasis, and only in advanced age do senescent cells accumulate to an organism's detriment.

Keywords: aging; apoptosis; cancer; embryogenesis; senescence.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Apoptosis*
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Cellular Senescence*
  • Humans
  • Signal Transduction
  • Stress, Physiological