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There is evidence of beneficial effects of angiotensin converting enzyme (ACE) inhibitors on aspects related to frailty, such as physical function, even in those without cardiovascular disease. This study aimed to longitudinally investigate the effect of an ACE inhibitor on frailty in aging male and female mice. Frailty was assessed with a clinical frailty index (FI) which quantifies health-related deficits in middle-aged (9\u201313 months) and older (16\u201325 months) mice. Chronic treatment with enalapril (30 mg\/kg\/day in feed) attenuated frailty in middle-aged and older female mice, and older male mice, without a long-term effect on blood pressure. Enalapril treatment resulted in a reduction in the proinflammatory cytokines interleukin (IL)-1\u03b1, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a in older female mice, and an increase in the anti-inflammatory cytokine IL-10 in older male mice compared with control animals. These sex-specific effects on inflammation may contribute to the protective effects of enalapril against frailty. This is the first study to examine the longitudinal effect of an intervention on the FI in mice, and provides preclinical evidence that enalapril may delay the onset of frailty, even when started later in life.<\/jats:p>","DOI":"10.1093\/gerona\/gly219","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T12:22:11Z","timestamp":1537878131000},"page":"1149-1157","source":"Crossref","is-referenced-by-count":74,"title":["Chronic Treatment With the ACE Inhibitor Enalapril Attenuates the Development of Frailty and Differentially Modifies Pro- and Anti-inflammatory Cytokines in Aging Male and Female C57BL\/6 Mice"],"prefix":"10.1093","volume":"74","author":[{"given":"Kaitlyn","family":"Keller","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Heinze-Milne","sequence":"additional","affiliation":[{"name":"School of Health and Human Performance, Dalhousie University, Halifax, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Grandy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, Canada"},{"name":"School of Health and Human Performance, Dalhousie University, Halifax, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E","family":"Howlett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, Canada"},{"name":"Department of Medicine (Geriatric Medicine), Dalhousie University, Halifax, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,25]]},"reference":[{"key":"2019071211160880600_CIT0001","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1093\/gerona\/62.7.722","article-title":"Frailty in relation to the accumulation of deficits","volume":"62","author":"Rockwood","year":"2007","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2019071211160880600_CIT0002","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/S0047-6374(02)00082-9","article-title":"The mortality rate as a function of accumulated deficits in a frailty index","volume":"123","author":"Mitnitski","year":"2002","journal-title":"Mech Ageing Dev"},{"key":"2019071211160880600_CIT0003","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1503\/cmaj.110626","article-title":"Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey","volume":"138","author":"Rockwood","year":"2011","journal-title":"Can Med Assoc J"},{"key":"2019071211160880600_CIT0004","doi-asserted-by":"publisher","first-page":"43068","DOI":"10.1038\/srep43068","article-title":"A frailty index based on deficit accumulation quantifies mortality risk in humans and in mice","volume":"7","author":"Rockwood","year":"2017","journal-title":"Sci Rep"},{"key":"2019071211160880600_CIT0005","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1093\/gerona\/59.12.1310","article-title":"Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian Study of Health and Aging","volume":"59","author":"Rockwood","year":"2004","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2019071211160880600_CIT0006","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.jamda.2015.12.016","article-title":"Frailty: an emerging public health priority","volume":"17","author":"Cesari","year":"2016","journal-title":"J Am Med Dir Assoc"},{"key":"2019071211160880600_CIT0007","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1093\/ageing\/afw247","article-title":"Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies","volume":"46","author":"Puts","year":"2017","journal-title":"Age Ageing"},{"key":"2019071211160880600_CIT0008","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.maturitas.2012.10.010","article-title":"Emerging drug therapies for frailty","volume":"74","author":"Jeffery","year":"2013","journal-title":"Maturitas"},{"key":"2019071211160880600_CIT0009","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.pcad.2014.07.004","article-title":"Therapeutic interventions for frail elderly patients: part I. 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