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Aging is one of the risk factors for numerous maladies such as metabolic disorder and frailty, which are exacerbated under obesity. Thus, therapeutic approaches that address obesity to ultimately improve affected individuals\u2019 quality of life and extend their lifespan are needed. We previously reported that the every other day (EOD) fasting initiated late-life improved metabolic, musculoskeletal, and cognitive endpoints in standard rodent diet-fed mice. In the present study, using the same dietary intervention methodology, we tested if 2.5\u00a0months of EOD fasting could improve metabolic, physiological, and cognitive endpoints in mice after an 18\u00a0month obesogenic high-fat diet (HFD). The positive effects of EOD fasting were generally consistent across the endpoints; EOD fasting decreased total body mass, maintained more %lean mass, improved glucose tolerance and utilization, and improved neuromuscular function. In contrast to our previous study, grip strength, hippocampal-dependent memory, and renal hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) production were not improved by the HFD EOD fasting. Thus, efficacy for late-life initiated intermittent fasting to improve specific frailty markers may be partially dependent on nutritional compositions of the diet.<\/jats:p>","DOI":"10.1007\/s11357-022-00678-1","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T14:02:44Z","timestamp":1666792964000},"page":"1247-1262","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A long-term obesogenic high-fat diet in mice partially dampens the anti-frailty benefits of late-life intermittent fasting"],"prefix":"10.1007","volume":"45","author":[{"given":"Yoko O.","family":"Henderson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazmin","family":"Bithi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Link","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aili","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Baron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Maina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-7939","authenticated-orcid":false,"given":"Christopher","family":"Hine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"issue":"7","key":"678_CR1","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1111\/obr.12551","volume":"18","author":"GA Bray","year":"2017","unstructured":"Bray GA, et al. 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