Vol.: (0123456789) Biogerontology (2025) 26:102 https://doi.org/10.1007/s10522-025-10249-4 REVIEW ARTICLE ATM and p53 in aging and cancer: a double‑edged sword in genomic integrity Surya Nath Pandey · Muhammad Afzal · Jyoti Uikey · Subbulakshmi Ganesan · Swati Mishra · Pooja Bansal · Imran Kazmi · Sami I. Alzarea · Waleed Hassan Almalk · Kavita Goyal · Gaurav Gupta · Mohit Rana Received: 10 March 2025 / Accepted: 24 April 2025 © The Author(s), under exclusive licence to Springer Nature B.V. 2025 apoptosis. ATM and p53 mutations upset this equi- librium to cause genomic instability, therapy resist- ance, and tumor progression in the context of can- cer. Oncogene-induced senescence is bypassed by ATM inactivation, which allows cells to progress to become tumors, and p53 mutations allow for uncon- trolled proliferation and sensitivity to apoptosis. Abstract Maintaining genomic stability is essential for detecting DNA damage and activating appropri- ate responses such as repair, apoptosis, or senescence, primarily mediated by the ATM-p53 axis. ATM is the main sensor of double-strand breaks, and once activated, it will either promote the repair of dam- aged DNA or eliminate the damaged cells through S. N. Pandey  Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad 244001, Uttar Pradesh, India M. Afzal  Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442 Jeddah, Saudi Arabia J. Uikey  IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh 462044, India S. Ganesan  Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India S. Mishra  Department of Pharmacology, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to Be University), Bhubaneswar, Odisha 751003, India P. Bansal  Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India I. Kazmi  Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589 Jeddah, Saudi Arabia S. I. Alzarea  Department of Pharmacology, College of Pharmacy, Jouf University, 72341 Sakaka, Al-Jouf, Saudi Arabia W. H. Almalk  University Medical Clinic, Umm Al-Qura University, Makkah, Saudi Arabia K. Goyal  Department of Biotechnology, Graphic Era (Deemed to Be University), Clement Town, Dehradun 248002, India G. Gupta  Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India G. Gupta  Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates