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This effect is mediated through adenosine monophosphate\u2013activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.<\/jats:p>","DOI":"10.1126\/sciadv.ado1463","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T17:59:58Z","timestamp":1715968798000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":92,"title":["Ketogenic diet induces p53-dependent cellular senescence in multiple organs"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-6850","authenticated-orcid":true,"given":"Sung-Jen","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, TX, USA."},{"name":"Barshop Institute for Longevity and Aging Studies at UT Health San Antonio, San Antonio, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-566X","authenticated-orcid":true,"given":"Joseph R.","family":"Schell","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, TX, USA."},{"name":"Barshop Institute for Longevity and Aging Studies at UT Health San Antonio, San Antonio, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-4731","authenticated-orcid":true,"given":"E. 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