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Review
. 2025 May 5;26(3):104.
doi: 10.1007/s10522-025-10247-6.

CHIP and aging: a key regulator of proteostasis and cellular senescence

Surya Nath Pandey  1 , Neetu Agrawal  2 , Ehssan Moglad  3 , G Padma Priya  4 , Manish Srivastava  5 , Kattela Chennakesavulu  6 , Biswaranjan Mohanty  7 , Renu Arya  8 , Imran Kazmi  9 , Sami I Alzarea  10 , Waleed Hassan Almalk  11 , Kavita Goyal  12
Affiliations
Review

CHIP and aging: a key regulator of proteostasis and cellular senescence

Surya Nath Pandey et al. Biogerontology. .

Abstract

Degradation of proteostasis, mitochondrial function, and cellular stress resistance results in a build-up of damaged proteins, oxidative insult, and chronic inflammation, characteristic of aging. CHIP is essential for maintaining protein quality control and cellular homeostasis by having dual E3 ubiquitin ligase and co-chaperone activities. CHIP facilitates proteostasis by maintaining proteostasis in misfolded, aggregated proteins by promoting their degradation. Mitochondrial dysfunction, oxidative imbalance, and cellular senescence are caused by its age-associated decline and contribute to neurodegenerative, cardiovascular, and oncogenic disease pathogenesis. Examples of recent pharmacological and gene-based strategies to correct CHIP and restore stress resilience have been made. This review examines the multiple facets of the aging role of CHIP and its potential as an aging disease therapy target.

Keywords: Aging; Autophagic Regulation; CHIP; Cancer; Cardiovascular Aging; Cellular Senescence; Neurodegeneration; Ubiquitin–proteasome system.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable.

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