cGAS-STING pathway drives cellular senescence and inflammaging

Yali Chen; Kun Chen

doi:10.70401/acrt.2026.0026

cGAS-STING pathway drives cellular senescence and inflammaging

Yali Chen

Kun Chen

*Correspondence to: Kun Chen, State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University Shanghai 200127, China. E-mail: chenk@tongji.edu.cn

Ageing Cancer Res Treat. 2026;3:202615. 10.70401/acrt.2026.0026

Received: March 31, 2026Accepted: June 12, 2026Published: June 15, 2026

This article belongs to the Special lssue Inflammation in Aging and Tumorigenesis

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Cellular senescence is a cell fate triggered by diverse endogenous and exogenous stresses, including DNA damage, telomere dysfunction, and metabolic dysregulation. It is characterized by irreversible cell cycle arrest and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). As a hallmark of ageing, senescence contributes to various physiological processes and is closely associated with the pathogenesis of age-related diseases. Specifically, senescent cells secrete SASP factors, which promote chronic inflammation, and propagate senescence to neighboring normal cells. DNA damage, a crucial inducer of cellular senescence and inflammation, often leads to the accumulation of cytosolic DNA. The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS-STING) pathway has emerged as a critical mechanism for detecting such intracellular DNA, and its excessive activation is strongly associated with senescence and age-related chronic inflammation (inflammaging). Accumulating evidence indicates that multiple factors can trigger cGAS-STING signaling, thereby stimulating inflammatory responses and accelerating cellular senescence. In this review, we summarize recent advances in understanding how cGAS-STING signaling orchestrates cellular senescence and inflammaging. We outline the key hallmarks and triggers of cellular senescence, with particular emphasis on the role of cGAS in age-related inflammatory diseases. Finally, we discuss that targeting cGAS-STING pathway may pave new ways for therapeutic strategies to mitigate cellular senescence-associated diseases.

Keywords

Cellular senescence, inflammaging, cGAS, STING, DNA damage

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Chen Y, Chen K. cGAS-STING pathway drives cellular senescence and inflammaging. Ageing Cancer Res Treat. 2026;3:202615. https://doi.org/10.70401/acrt.2026.0026