{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:45:50Z","timestamp":1776339950745,"version":"3.51.2"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aging leads to a decline in muscle mass and strength, contributing to frailty and decreased quality of life. Sirolimus (rapamycin) , an mTOR inhibitor, has shown potential in preclinical studies to extend lifespan and improve health span. This study evaluates the safety and efficacy of once-weekly sirolimus (rapamycin) administration on muscle strength and endurance in older adults engaged in a 13-week exercise program.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, double-blind, placebo-controlled trial will enroll 40 participants aged 65\u201385. Participants will be randomly assigned to receive either sirolimus (rapamycin) 6 mg\/week or placebo for 13 weeks, in conjunction with an at-home exercise program. The primary outcome measure is the change in muscle strength and endurance, assessed by the 30-Second Chair-Stand Test. Secondary outcome measures include adverse events, changes in muscle strength and endurance as measured by the 6-min walk test, handgrip strength, and participant-reported outcomes using the SF-36 survey. Assessments will be conducted at baseline, mid-intervention (week 6), and post-intervention (week 13). Blood samples will be collected for hematology and biochemistry analyses, including full blood count, urea and electrolytes, liver function tests, HbA1c, lipids, serum IGF-1, and hs-CRP. DNA methylation will be analyzed using TruDiagnostic\u2122 to explore changes in biological age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study aims to provide insights into the potential benefits of intermittent sirolimus (rapamycin) administration on muscle performance in older adults. By alternating periods of mTOR inhibition through rapamycin and activation via exercise, this study will explore a novel approach to enhancing muscle strength and endurance in the aging population. The results could have significant implications for developing interventions to improve physical function and overall health outcomes in older adults. Safety and tolerability will also be closely monitored to ensure the feasibility of this regimen for wider application.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Australia New Zealand Clinical Trials Registry, ACTRN12624000790549. Registered on 26 June 2024\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?ACTRN=12624000790549\">https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?ACTRN=12624000790549<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-024-08490-2","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T04:01:37Z","timestamp":1727755297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A single-center, double-blind, randomized, placebo-controlled, two-arm study to evaluate the safety and efficacy of once-weekly sirolimus (rapamycin) on muscle strength and endurance in older adults following a 13-week exercise program"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-2039","authenticated-orcid":false,"given":"Brad","family":"Stanfield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matt","family":"Kaeberlein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Leroux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Arroll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"issue":"1","key":"8490_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.14336\/AD.2017.0202","volume":"9","author":"B Strasser","year":"2018","unstructured":"Strasser B, et al. 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The ethics reference number for this approval is 2024 FULL 20084. This approval includes the completion of non-standard conditions before the commencement of the study, ensuring compliance with HDEC requirements.This study will be conducted in accordance with the protocol and with the following:\u2022 Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organisations of Medical Sciences (CIOMS) international ethical guidelines.\u2022 Applicable ICH Good Clinical Practice Guidelines (GCP)\u2022 Applicable laws and regulations.New Zealand National Ethics Advisory Committee (NEAC) Guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. This manuscript does not contain any details, images, or videos relating to an individual person. If requested, the authors are willing to provide a model consent form and other related documentation given to participants and authorized surrogates.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There are no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"642"}}