The ticking of aging clocks

• Published in: Trends in endocrinology and metabolism 2024-01, Vol.35 (1), p.11-22
• Main Author: Han, Jing-Dong J.
• Format: Article
• Language: English
• Subjects: Aging - genetics; aging clock; Cellular Senescence - genetics; counting unit; DNA damage; DNA Damage - genetics; epigenetic regulation; Humans; metabolic coupling; Reactive Oxygen Species; senescence
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2023.09.007

Aging clocks determine aging rate by the difference between predicted and chronological age.Clock-determined aging rate is associated with health, morbidity, and mortality.The DNA damage response and its associated epigenetic changes may be the fundamental counting unit of aging clocks.Cellular senescence could be the next upper-level unit of aging clocks.Oxidative stress and inflammation contribute to DNA damage and accelerate aging clocks. 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. 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.