Hallmark of aging
Cellular Senescence
Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
What it is
Senescent cells have exited the cell cycle but remain metabolically active and resistant to apoptosis. They secrete a complex mix of cytokines, chemokines, proteases, and growth factors — the senescence-associated secretory phenotype (SASP) — that can drive tissue remodelling, inflammation, and senescence in nearby cells.
Why it matters in aging
Senescent-cell burden rises with age. Genetic clearance of p16Ink4a- high cells in mice extends median lifespan and delays multiple age-related pathologies. The SASP is a major driver of chronic, low-grade inflammation (“inflammaging”).
Mechanisms
- Triggers: replicative exhaustion, oncogene activation, DNA damage, mitochondrial dysfunction, proteostatic stress.
- Enforcement: p16Ink4a/Rb and p53/p21 pathways; persistent DNA-damage signalling.
- SASP regulation: NF-κB, mTOR, cGAS–STING (cytosolic DNA sensing).
What’s being studied
Senolytics — including the dasatinib + quercetin combination and fisetin — selectively kill senescent cells in mouse models. Human trials are early but expanding (diabetic kidney disease, idiopathic pulmonary fibrosis, frailty). Senomorphics (e.g. rapamycin, JAK inhibitors) blunt the SASP without killing the cells.
Related entries
See also: Senolytics, Chronic inflammation, Telomere attrition.
References
- Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019).
- Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020).