The ticking of aging clocks

Trends Endocrinol Metab. 2024 Jan;35(1):11-22. doi: 10.1016/j.tem.2023.09.007. Epub 2023 Oct 23.


Computational models that measure biological age and aging rate regardless of chronological age are called aging clocks. The underlying counting mechanisms of the intrinsic timers of these clocks are still unclear. Molecular mediators and determinants of aging rate point to the key roles of DNA damage, epigenetic drift, and inflammation. Persistent DNA damage leads to cellular senescence and the senescence-associated secretory phenotype (SASP), which induces cytotoxic immune cell infiltration; this further induces DNA damage through reactive oxygen and nitrogen species (RONS). I discuss the possibility that DNA damage (or the response to it, including epigenetic changes) is the fundamental counting unit of cell cycles and cellular senescence, that ultimately accounts for cell composition changes and functional decline in tissues, as well as the key intervention points.

Keywords: DNA damage; aging clock; counting unit; epigenetic regulation; metabolic coupling; senescence.

Publication types

  • Review

MeSH terms

  • Aging* / genetics
  • Cellular Senescence* / genetics
  • DNA Damage / genetics
  • Humans
  • Reactive Oxygen Species


  • Reactive Oxygen Species