{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:37:11Z","timestamp":1789202231462,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8\u2014Project Age-It: \u201cAgeing Well in an Ageing Society\u201d","award":["DM 1557 11.10.2022"],"award-info":[{"award-number":["DM 1557 11.10.2022"]}]},{"name":"Next Generation EU","award":["DM 1557 11.10.2022"],"award-info":[{"award-number":["DM 1557 11.10.2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Nowadays, scientists are making efforts to elucidate the mechanisms involved in the phenotypic changes underlying the aging process in order to develop favorable therapeutical interventions. Epigenetic modifications, in particular DNA methylation, play a crucial role in the aging process, and this parameter has been used to set epigenetic clocks, algorithms that predict an individual\u2019s biological age based on a defined set of CpGs. In this review, we focus on the most recent literature to discuss the use of epigenetic clocks in the context of cognitive decline and dysregulation of Alzheimer\u2019s disease (AD)-related gene expression. We have summarized all published scientific papers in which epigenetic clocks have been applied to measure age acceleration in blood and brain specimens from patients affected with AD. Progressive age acceleration, consistent with a specific DNA methylation signature, was observed in patients affected by AD, and it was correlated with the onset of complex diseases, mitochondrial alterations, dementia and cognitive decline, even in the early stages of these conditions. The use of epigenetic clocks might be a valuable biomarker to enable an earlier identification of ideal measures to reverse modifications caused by aging and to mitigate multiple aspects of disease\/aging mechanisms.<\/jats:p>","DOI":"10.3390\/genes16060679","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T09:22:41Z","timestamp":1748596961000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenetic Clocks and Their Prospective Application in the Complex Landscape of Aging and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Annamaria","family":"Cerantonio","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Maria","family":"Greco","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"},{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Citrigno","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selene","family":"De Benedittis","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9147-9752","authenticated-orcid":false,"given":"Antonio","family":"Qualtieri","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0758-1835","authenticated-orcid":false,"given":"Raffaele","family":"Maletta","sequence":"additional","affiliation":[{"name":"Regional Neurogenetic Centre (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, CZ, Italy"},{"name":"Association for Neurogenetic Research (ARN), 88046 Lamezia Terme, CZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-2216","authenticated-orcid":false,"given":"Alberto","family":"Montesanto","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-9748","authenticated-orcid":false,"given":"Giuseppe","family":"Passarino","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Spadafora","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5769-4582","authenticated-orcid":false,"given":"Francesca","family":"Cavalcanti","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), 87050 Mangone, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E4104","DOI":"10.1073\/pnas.1506264112","article-title":"Quantification of biological aging in young adults","volume":"112","author":"Belsky","year":"2015","journal-title":"Proc. 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