{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:16:39Z","timestamp":1791414999966,"version":"4.3.3"},"reference-count":38,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Translational Geroscience Network","award":["R33AG061456"],"award-info":[{"award-number":["R33AG061456"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37AG013925"],"award-info":[{"award-number":["R37AG013925"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AG062413"],"award-info":[{"award-number":["P01AG062413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Association Part the Cloud Program"},{"name":"Robert and Arlene Kogod"},{"name":"Connor Group"},{"name":"Robert J. and Theresa W. 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The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell\/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.<\/jats:p>","DOI":"10.1210\/clinem\/dgaa728","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T10:52:11Z","timestamp":1604659931000},"page":"e1481-e1487","source":"Crossref","is-referenced-by-count":130,"title":["New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-7145","authenticated-orcid":false,"given":"Tamar","family":"Tchkonia","sequence":"first","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-3455","authenticated-orcid":false,"given":"Allyson K","family":"Palmer","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, 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