Cellular Senescence: The Sought or the Unwanted?

Trends Mol Med. 2018 Oct;24(10):871-885. doi: 10.1016/j.molmed.2018.08.002. Epub 2018 Aug 25.

Abstract

Cellular senescence is a process that results in irreversible cell-cycle arrest, and is thought to be an autonomous tumor-suppressor mechanism. During senescence, cells develop distinctive metabolic and signaling features, together referred to as the senescence-associated secretory phenotype (SASP). The SASP is implicated in several aging-related pathologies, including various malignancies. Accumulating evidence argues that cellular senescence acts as a double-edged sword in human cancer, and new agents and innovative strategies to tackle senescent cells are in development pipelines to counter the adverse effects of cellular senescence in the clinic. We focus on recent discoveries in senescence research and SASP biology, and highlight the potential of SASP suppression and senescent cell clearance in advancing precision medicine.

Keywords: aging-related pathology; cancer; cellular senescence; senescence-associated secretory phenotype; senolytics; therapy-induced senescence.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cell Cycle Checkpoints / drug effects
  • Cell Division / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cellular Senescence / drug effects
  • Cellular Senescence / genetics*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phenotype
  • Precision Medicine / methods*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Signal Transduction
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics

Substances

  • Antineoplastic Agents
  • Cytokines
  • Heat-Shock Proteins
  • Neoplasm Proteins
  • Protein Kinases