Senescent cells—those that have stopped dividing—adopt distinct molecular profiles depending on how they became senescent. Primary senescence (triggered by direct DNA damage) activates fibrosis and tissue-remodeling programs, while secondary senescence (induced by signals from other senescent cells) drives inflammatory pathways. Both share conserved stress-response mechanisms, revealing that senescence heterogeneity fundamentally shapes how these cells contribute to aging.
Key Points
- Primary and secondary senescence activate fundamentally different gene programs
- Primary senescence favors fibrosis; secondary senescence favors inflammation
- HMGA1, NFKB1, JUNB regulate context-specific senescence trajectories
Longevity Analysis
Senescent cells accumulate throughout life and drive chronic inflammation and tissue dysfunction—core mechanisms underlying age-related disease. This work demonstrates that senescence is not a single state but a collection of distinct cellular phenotypes with different inflammatory and tissue-remodeling signatures. Understanding which senescence programs dominate in specific tissues and contexts is essential for developing interventions that selectively clear harmful senescent populations while preserving those that support repair. The identification of regulatory nodes (HMGA1, NFKB1, JUNB) specific to secondary senescence opens therapeutic avenues for dampening the paracrine amplification of cellular aging—the process by which senescent cells prime neighboring cells toward senescence, accelerating systemic decline.
Original published by Wiley Aging Cell, by Dong‐Hyun Jang, Eunha Shim, Ji‐Won Shin, Seokho Kim, Serban Ciotlos, Hyun Jung Kim, Tae‐Hwan Gil, Yumin Kim, Ok Hee Jeon .