Cellular Senescence

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title: Cellular Senescence slug: cellular-senescence category: hallmarks summary: Stable cell-cycle arrest accompanied by a pro-inflammatory secretome (SASP) that propagates dysfunction to neighbouring tissue. lastUpdated: 2026-05-17 tags: [senescence, SASP, p16, senolytics] 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)."

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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 p16^Ink4a- 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: p16^Ink4a/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.