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Review
. 2024 Jun:101:44-57.
doi: 10.1016/j.semcancer.2024.05.001. Epub 2024 May 17.

p53/MDM2 signaling pathway in aging, senescence and tumorigenesis

Youyi Huang  1 , Xiaofang Che  1 , Peter W Wang  2 , Xiujuan Qu  3
Affiliations
Review

p53/MDM2 signaling pathway in aging, senescence and tumorigenesis

Youyi Huang et al. Semin Cancer Biol. 2024 Jun.

Abstract

A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.

Keywords: Aging; Carcinogenesis; MDM2; Senescence; p53.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest.

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