The signals and pathways activating cellular senescence

Ittai Ben-Porath*, Robert A. Weinberg

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

837 Scopus citations


Cellular senescence is a program activated by normal cells in response to various types of stress. These include telomere uncapping, DNA damage, oxidative stress, oncogene activity and others. Senescence can occur following a period of cellular proliferation or in a rapid manner in response to acute stress. Once cells have entered senescence, they cease to divide and undergo a series of dramatic morphologic and metabolic changes. Cellular senescence is thought to play an important role in tumor suppression and to contribute to organismal aging, but a detailed description of its physiologic occurrence in vivo is lacking. Recent studies have provided important insights regarding the manner by which different stresses and stimuli activate the signaling pathways leading to senescence. These studies reveal that a population of growing cells may suffer from a combination of different physiologic stresses acting simultaneously. The signaling pathways activated by these stresses are funneled to the p53 and Rb proteins, whose combined levels of activity determine whether cells enter senescence. Here we review recent advances in our understanding of the stimuli that trigger senescence, the molecular pathways activated by these stimuli, and the manner by which these signals determine the entry of a population of cells into senescence.

Original languageAmerican English
Pages (from-to)961-976
Number of pages16
JournalInternational Journal of Biochemistry and Cell Biology
Issue number5 SPEC. ISS.
StatePublished - May 2005
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Kimberly Hartwell, Lynne Waldman, Christina Scheel and Priya Rai for commenting on the manuscript. IB is supported by an Anna Fuller Fund Postdoctoral Fellowship and by a Leukemia and Lymphoma Foundation Special Fellowship.


  • ARF
  • DNA damage
  • Oxidative stress
  • Rb
  • Senescence
  • Telomeres
  • p16
  • p53


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