{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:14:31Z","timestamp":1789460071707,"version":"build-2803163510"},"reference-count":320,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["UKWN"],"award-info":[{"award-number":["UKWN"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Sciences and Engineering Council of Canada","award":["UKWN"],"award-info":[{"award-number":["UKWN"]}]},{"name":"Saskatchewan Research Chair in Alzheimer Disease and Related Dementias funded by the Alzheimer Society of Saskatchewan and the Saskatchewan Health Research Foundation","award":["UKWN"],"award-info":[{"award-number":["UKWN"]}]},{"name":"University of Saskatchewan College of Graduate and Postdoctoral Studies","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Vanier Canada Graduate Scholarship","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Caloric restriction (CR), the reduction of caloric intake without inducing malnutrition, is the most reproducible method of extending health and lifespan across numerous organisms, including humans. However, with nearly one-third of the world\u2019s population overweight, it is obvious that caloric restriction approaches are difficult for individuals to achieve. Therefore, identifying compounds that mimic CR is desirable to promote longer, healthier lifespans without the rigors of restricting diet. Many compounds, such as rapamycin (and its derivatives), metformin, or other naturally occurring products in our diets (nutraceuticals), induce CR-like states in laboratory models. An alternative to CR is the removal of specific elements (such as individual amino acids) from the diet. Despite our increasing knowledge of the multitude of CR approaches and CR mimetics, the extent to which these strategies overlap mechanistically remains unclear. Here we provide an update of CR and CR mimetic research, summarizing mechanisms by which these strategies influence genome function required to treat age-related pathologies and identify the molecular fountain of youth.<\/jats:p>","DOI":"10.3390\/ijms21239220","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T11:15:43Z","timestamp":1606994143000},"page":"9220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-6956","authenticated-orcid":false,"given":"Carla","family":"Almend\u00e1riz-Palacios","sequence":"first","affiliation":[{"name":"Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 4A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell D.","family":"Mousseau","sequence":"additional","affiliation":[{"name":"Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Eskiw","sequence":"additional","affiliation":[{"name":"Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 4A8, Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe E.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1042\/CS20100476","article-title":"Aging and vascular endothelial function in humans","volume":"120","author":"Seals","year":"2011","journal-title":"Clin. 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