“ Cellular senescence is a stable form of cell-cycle arrest induced by diverse intrinsic and extrinsic stimuli. ”
BUFFALO, NY — July 7, 2026 — A new review was published in Volume 18 of Aging on June 22, 2026, titled “ The multifaceted inducers of cellular senescence .”
The review was led by first author Hilah Gal and corresponding author Valery Krizhanovsky from the Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel .
Cellular senescence is a fundamental biological process in which damaged or stressed cells permanently stop dividing while remaining metabolically active. This response plays an essential role in suppressing tumor formation, supporting embryonic development, facilitating wound healing, and maintaining tissue integrity. However, as people age, senescent cells accumulate because they are no longer efficiently cleared by the immune system. Their persistence contributes to chronic inflammation, tissue dysfunction, cancer, and many age-related diseases.
In this comprehensive review, the authors examine the diverse biological stimuli that trigger cellular senescence and describe how seemingly different stimuli ultimately converge on common molecular pathways that establish stable growth arrest. Rather than viewing senescence as a single process, the review emphasizes its remarkable biological diversity and the importance of understanding how different initiating events shape distinct senescent cell phenotypes.
The review discusses several major biological inducers of cellular senescence. One of the best-established mechanisms is telomere attrition, in which repeated cell division gradually shortens chromosome ends until they trigger a persistent DNA damage response. Other important stimuli include direct DNA damage caused by ionizing radiation, ultraviolet light, chemotherapy, and oxidative injury, all of which activate cellular pathways that permanently halt proliferation.
The authors also highlight the important roles of oxidative stress and mitochondrial dysfunction. Excessive reactive oxygen species can damage DNA, accelerate telomere shortening, disrupt mitochondrial function, and amplify inflammatory signaling. These interconnected processes reinforce senescence while contributing to many of the chronic changes associated with aging.
Another major focus is oncogene-induced senescence, an intrinsic defense mechanism that prevents potentially cancerous cells from continuing to divide after abnormal activation of cancer-promoting genes. Although this response initially suppresses tumor formation, senescent cells that persist over time may later promote cancer progression through the secretion of inflammatory signaling molecules collectively known as the senescence-associated secretory phenotype (SASP).
Beyond these classical pathways, the review explores several less widely recognized forms of senescence. These include senescence-induced senescence, in which senescent cells promote senescence in neighboring cells through inflammatory signaling; fusion-induced senescence, which contributes to placental development and protection against viral infection; and developmental senescence, a tightly regulated physiological program that helps shape tissues and organs during embryonic development. Together, these findings demonstrate that senescence is not solely a response to damage but also serves important functions throughout normal biology.
The authors further discuss how recent advances in single-cell technologies are revealing that senescent cells differ substantially across tissues and disease states. This growing appreciation of senescence heterogeneity may help explain why some senescent cells promote tissue repair whereas others drive chronic inflammation and degeneration, opening new opportunities for therapies that selectively target harmful senescent cell populations.
“ Understanding the varied stimuli and their underlying mechanisms of senescence induction is crucial for revealing the heterogeneity of senescent cells and developing interventions that modulate senescence during aging and disease .”
According to the authors, future therapeutic strategies will likely require distinguishing between different types of senescent cells rather than treating senescence as a single biological state. A better understanding of how individual triggers influence senescence may enable the development of interventions that selectively eliminate harmful senescent cells while preserving the beneficial roles of senescence in tissue repair, development, and tumor suppression.
Overall, this review provides a comprehensive overview of the diverse biological mechanisms that initiate cellular senescence and illustrates how these pathways influence aging, cancer, tissue regeneration, and chronic disease. By integrating current knowledge on the many inducers of senescence, the authors offer a valuable framework for advancing future research and developing more targeted approaches to promote healthy aging.
Paper DOI : https://doi.org/10.18632/aging.206391
Corresponding author: Valery Krizhanovsky – valery.krizhanovsky@weizmann.ac.il
Keywords: aging, cell senescence
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
Click here to subscribe to Aging publication updates.
For media inquiries, please contact media@impactjournals.com .
Aging-US
Literature review
Cells
The multifaceted inducers of cellular senescence
22-Jun-2026
The authors declare that they have no conflicts of interest.