{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:07:06Z","timestamp":1793506026328,"version":"4.5.0"},"reference-count":87,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["741989"],"award-info":[{"award-number":["741989"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023341","name":"Max Planck Instituut voor Psycholingu\u00efstiek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["268739"],"award-info":[{"award-number":["268739"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2030\u2013390661388"],"award-info":[{"award-number":["EXC 2030\u2013390661388"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004189","name":"Max-Planck-Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.molmet.2024.101902","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T12:13:26Z","timestamp":1707826406000},"page":"101902","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"special_numbering":"C","title":["Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension"],"prefix":"10.1016","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-7074","authenticated-orcid":false,"given":"Maarouf","family":"Baghdadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-2331","authenticated-orcid":false,"given":"Tobias","family":"Nespital","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5043-8145","authenticated-orcid":false,"given":"Carolina","family":"Monz\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4483-3701","authenticated-orcid":false,"given":"Joris","family":"Deelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-5346","authenticated-orcid":false,"given":"Sebastian","family":"Gr\u00f6nke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-0094","authenticated-orcid":false,"given":"Linda","family":"Partridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molmet.2024.101902_bib1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41586-018-0457-8","article-title":"Facing up to the global challenges of ageing","volume":"561","author":"Partridge","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.101902_bib2","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1038\/s41598-021-82459-y","article-title":"Data-driven identification of ageing-related diseases from electronic health records","volume":"11","author":"Kuan","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.molmet.2024.101902_bib3","doi-asserted-by":"crossref","first-page":"R741","DOI":"10.1016\/j.cub.2012.07.024","article-title":"Ageing as a risk factor for disease","volume":"22","author":"Niccoli","year":"2012","journal-title":"Curr Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib4","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s43587-021-00080-0","article-title":"The economic value of targeting aging","volume":"1","author":"Scott","year":"2021","journal-title":"Nat Aging"},{"key":"10.1016\/j.molmet.2024.101902_bib5","first-page":"21","article-title":"Biological mechanisms of aging predict age-related disease co-occurrence in patients","author":"Fraser","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib6","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s11357-008-9048-1","article-title":"Design of aging intervention studies: the NIA interventions testing program","volume":"30","author":"Nadon","year":"2008","journal-title":"Age"},{"key":"10.1016\/j.molmet.2024.101902_bib7","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","article-title":"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton","volume":"14","author":"Sarbassov","year":"2004","journal-title":"Curr Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/gerona\/glq178","article-title":"Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice","volume":"66","author":"Miller","year":"2011","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.molmet.2024.101902_bib9","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/acel.12194","article-title":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent\u00a0and\u00a0metabolically distinct from dietary restriction","volume":"13","author":"Miller","year":"2014","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib10","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"Harrison","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.101902_bib11","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.16351","article-title":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","volume":"5","author":"Bitto","year":"2016","journal-title":"Elife"},{"key":"10.1016\/j.molmet.2024.101902_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2000559","article-title":"MTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells","volume":"2","author":"Chen","year":"2009","journal-title":"Sci Signal"},{"key":"10.1016\/j.molmet.2024.101902_bib13","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.4161\/cc.10.24.18486","article-title":"Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice","volume":"10","author":"Anisimov","year":"2011","journal-title":"Cell Cycle"},{"key":"10.1016\/j.molmet.2024.101902_bib15","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3009892","article-title":"mTOR inhibition improves immune function in the elderly","volume":"6","author":"Mannick","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.molmet.2024.101902_bib14","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s43587-023-00416-y","article-title":"Targeting the biology of aging with mTOR inhibitors","volume":"3","author":"Mannick","year":"2023","journal-title":"Nat Aging"},{"key":"10.1016\/j.molmet.2024.101902_bib16","doi-asserted-by":"crossref","first-page":"112166","DOI":"10.1016\/j.exger.2023.112166","article-title":"Rapamycin, the only drug that has been consistently demonstrated to increase mammalian longevity. An update","volume":"176","author":"Sharp","year":"2023","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.molmet.2024.101902_bib17","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1474-9726.2012.00832.x","article-title":"Rapamycin slows aging in mice","volume":"11","author":"Wilkinson","year":"2012","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib18","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1126\/science.1215135","article-title":"Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity","volume":"335","author":"Lamming","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.molmet.2024.101902_bib19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/acel.12405","article-title":"Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system","volume":"15","author":"Arriola Apelo","year":"2016","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib20","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1542\/peds.108.4.e73","article-title":"Antipyretic efficacy of an initial 30-mg\/kg loading dose of acetaminophen versus a 15-mg\/kg maintenance dose","volume":"108","author":"Tr\u00e9luyer","year":"2001","journal-title":"Pediatrics"},{"key":"10.1016\/j.molmet.2024.101902_bib21","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.bja.2018.03.038","article-title":"Continuous epidural infusion vs programmed intermittent epidural bolus for labour analgesia: a prospective, controlled, before-and-after cohort study of labour outcomes","volume":"121","author":"Bullingham","year":"2018","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.molmet.2024.101902_bib22","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/bja\/ael157","article-title":"Intermittent vs continuous administration of epidural ropivacaine with fentanyl for analgesia during labour","volume":"97","author":"Fettes","year":"2006","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.molmet.2024.101902_bib23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/CCM.0000000000002771","article-title":"Intermittent versus continuous and intermittent medications for pain and sedation after pediatric cardiothoracic surgery; A randomized controlled trial","volume":"46","author":"Penk","year":"2018","journal-title":"Crit Care Med"},{"key":"10.1016\/j.molmet.2024.101902_bib24","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1182\/blood-2014-11-611426","article-title":"Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets","volume":"125","author":"Sehgal","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.molmet.2024.101902_bib25","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1016\/S2352-3018(21)00322-2","article-title":"Forgiveness of an intermittent HIV treatment strategy","volume":"9","author":"Parienti","year":"2022","journal-title":"Lancet HIV"},{"key":"10.1016\/j.molmet.2024.101902_bib26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1093\/gerona\/glw064","article-title":"Intermittent administration of rapamycin extends the life span of female C57BL\/6J mice","volume":"71","author":"Arriola Apelo","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.molmet.2024.101902_bib27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.molcel.2006.03.029","article-title":"Prolonged rapamycin treatment inhibits mTORC2 assembly and akt\/PKB","volume":"22","author":"Sarbassov","year":"2006","journal-title":"Mol Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib28","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13269","article-title":"Rapamycin-mediated mouse lifespan extension: late-life dosage regimes with sex-specific effects","volume":"19","author":"Strong","year":"2020","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib29","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s43587-022-00278-w","article-title":"Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy","volume":"2","author":"Juricic","year":"2022","journal-title":"Nat Aging"},{"key":"10.1016\/j.molmet.2024.101902_bib30","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abo5482","article-title":"Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna","volume":"8","author":"Shindyapina","year":"2022","journal-title":"Sci Adv"},{"key":"10.1016\/j.molmet.2024.101902_bib31","doi-asserted-by":"crossref","first-page":"eade8137","DOI":"10.1126\/sciadv.ade8137","article-title":"Reduced insulin signaling in neurons induces sex-specific health benefits","volume":"9","author":"Baghdadi","year":"2023","journal-title":"Sci Adv"},{"key":"10.1016\/j.molmet.2024.101902_bib32","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jgg.2014.06.002","article-title":"Lifespan modulation in mice and the confounding effects of genetic background","volume":"41","author":"Mulvey","year":"2014","journal-title":"J Genet Genom"},{"key":"10.1016\/j.molmet.2024.101902_bib33","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.mad.2004.07.003","article-title":"Statistical methods for testing effects on \u2018maximum lifespan\u2019","volume":"125","author":"Wang","year":"2004","journal-title":"Mech Ageing Dev"},{"key":"10.1016\/j.molmet.2024.101902_bib34","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1136\/bmj.328.7447.1073","article-title":"The logrank test","volume":"328","author":"Bland","year":"2004","journal-title":"BMJ"},{"key":"10.1016\/j.molmet.2024.101902_bib35","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1161\/CIRCULATIONAHA.108.822403","article-title":"Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging","volume":"119","author":"Dai","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.molmet.2024.101902_bib36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","article-title":"The global epidemiology of hypertension","volume":"16","author":"Mills","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.molmet.2024.101902_bib37","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/acel.12109","article-title":"Late-life rapamycin treatment reverses age-related heart dysfunction","volume":"12","author":"Flynn","year":"2013","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib38","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/acel.12203","article-title":"Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart","volume":"13","author":"Dai","year":"2014","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib39","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1172\/JCI67674","article-title":"Rapamycin extends murine lifespan but has limited effects on aging","volume":"123","author":"Neff","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1016\/j.molmet.2024.101902_bib40","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.cmet.2013.03.003","article-title":"Molecular and genetic crosstalks between mTOR and ERR\u03b1 are key determinants of rapamycin-induced nonalcoholic fatty liver","volume":"17","author":"Chaveroux","year":"2013","journal-title":"Cell Metab"},{"key":"10.1016\/j.molmet.2024.101902_bib41","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/S1073-4449(00)70001-X","article-title":"The nature of chronic progressive nephropathy in aging rats","volume":"7","author":"Abrass","year":"2000","journal-title":"Adv Ren Replace Ther"},{"key":"10.1016\/j.molmet.2024.101902_bib42","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1097\/TP.0b013e31824bf1f0","article-title":"Sirolimus-associated testicular toxicity: detrimental but reversible","volume":"93","author":"Rovira","year":"2012","journal-title":"Transplantation"},{"key":"10.1016\/j.molmet.2024.101902_bib43","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1080\/01926230590934304","article-title":"STP position paper: best practice guideline for the routine pathology evaluation of the immune system","volume":"33","author":"Haley","year":"2005","journal-title":"Toxicol Pathol"},{"key":"10.1016\/j.molmet.2024.101902_bib44","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/01926230600865523","article-title":"Enhanced histopathology of the spleen","volume":"34","author":"Elmore","year":"2006","journal-title":"Toxicol Pathol"},{"key":"10.1016\/j.molmet.2024.101902_bib45","series-title":"Splenomegaly","author":"Chapman","year":"2022"},{"key":"10.1016\/j.molmet.2024.101902_bib46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0095192","article-title":"Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability","volume":"9","author":"Assarsson","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.molmet.2024.101902_bib47","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/s41591-019-0673-2","article-title":"Undulating changes in human plasma proteome profiles across the lifespan","volume":"25","author":"Lehallier","year":"2019","journal-title":"Nat Med"},{"key":"10.1016\/j.molmet.2024.101902_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000599","article-title":"A proteomic atlas of senescence-associated secretomes for aging biomarker development","volume":"18","author":"Basisty","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib49","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/ncb3195","article-title":"MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation","volume":"17","author":"Laberge","year":"2015","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib50","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/acel.12587","article-title":"Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism","volume":"16","author":"Wang","year":"2017","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib51","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1096\/fj.201801690R","article-title":"Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K\/AKT and MAPK\/ERK pathways","volume":"33","author":"Liang","year":"2019","journal-title":"FASEB J"},{"key":"10.1016\/j.molmet.2024.101902_bib52","doi-asserted-by":"crossref","first-page":"eaar4289","DOI":"10.1126\/scitranslmed.aar4289","article-title":"Rapamycin and Alzheimer's disease: time for a clinical trial?","volume":"11","author":"Kaeberlein","year":"2019","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.molmet.2024.101902_bib86","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1007\/s11357-023-00818-1","article-title":"Evaluation of off-label rapamycin use to promote healthspan in 333 adults","volume":"45","author":"Kaeberlein","year":"2023","journal-title":"GeroScience"},{"key":"10.1016\/j.molmet.2024.101902_bib87","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1067\/mcp.2001.112513","article-title":"Pharmacokinetic interaction between single oral doses of ditiazem and sirolimus in healthy volunteers\u22171","volume":"69","author":"Bottiger","year":"2001","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.molmet.2024.101902_bib53","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1742-7843.2009.00427.x","article-title":"Long-term administration of rapamycin reduces adiposity, but impairs glucose tolerance\u00a0in high-fat diet-fed KK\/HlJ mice","volume":"105","author":"Chang","year":"2009","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1016\/j.molmet.2024.101902_bib54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1093\/gerona\/glz157","article-title":"Differential effects of rapamycin on glucose metabolism in nine inbred strains","volume":"75","author":"Reifsnyder","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.molmet.2024.101902_bib55","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.2337\/db13-0106","article-title":"Evidence for rapamycin toxicity in pancreatic \u03b2-cells and a review of the underlying molecular mechanisms","volume":"62","author":"Barlow","year":"2013","journal-title":"Diabetes"},{"key":"10.1016\/j.molmet.2024.101902_bib56","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/acel.12097","article-title":"Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive","volume":"12","author":"Lamming","year":"2013","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib57","doi-asserted-by":"crossref","first-page":"28743","DOI":"10.3402\/pba.v5.28743","article-title":"Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy","volume":"5","author":"Bai","year":"2015","journal-title":"Pathobiol Aging Age Relat Dis"},{"key":"10.1016\/j.molmet.2024.101902_bib58","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/gerona\/glt056","article-title":"Rapamycin extends life and health in C57BL\/6 mice","volume":"69","author":"Zhang","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.molmet.2024.101902_bib59","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0126644","article-title":"Health effects of long-term rapamycin treatment: the impact on mouse health of enteric rapamycin treatment from four months of age throughout life","volume":"10","author":"Fischer","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.molmet.2024.101902_bib60","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1172\/JCI67674","article-title":"Rapamycin extends murine lifespan but has limited effects on aging","volume":"123","author":"Neff","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1016\/j.molmet.2024.101902_bib61","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41596-019-0256-1","article-title":"A toolbox for the longitudinal assessment of healthspan in aging mice","volume":"15","author":"Bellantuono","year":"2020","journal-title":"Nat Protoc"},{"key":"10.1016\/j.molmet.2024.101902_bib62","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13086","article-title":"Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment","volume":"19","author":"Quarles","year":"2020","journal-title":"Aging Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib63","doi-asserted-by":"crossref","first-page":"H1907","DOI":"10.1152\/ajpheart.00681.2008","article-title":"Genetic influence on electrocardiogram time intervals and heart rate in aging mice","volume":"296","author":"Xing","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.molmet.2024.101902_bib64","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cmet.2013.02.008","article-title":"Duration of rapamycin treatment has differential effects on metabolism in mice","volume":"17","author":"Fang","year":"2013","journal-title":"Cell Metab"},{"key":"10.1016\/j.molmet.2024.101902_bib65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-17942-7","article-title":"Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGF\u03b21 as regulators of hematopoietic ageing","volume":"11","author":"Valletta","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.molmet.2024.101902_bib66","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41586-021-03547-7","article-title":"An aged immune system drives senescence and ageing of solid organs","volume":"594","author":"Yousefzadeh","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.101902_bib67","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.immuni.2008.08.012","article-title":"The TSC-mTOR signaling pathway regulates the innate inflammatory response","volume":"29","author":"Weichhart","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.molmet.2024.101902_bib68","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaq1564","article-title":"TORC1 inhibition enhances immune function and reduces infections in the elderly","volume":"10","author":"Mannick","year":"2018","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.molmet.2024.101902_bib69","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.molmet.2024.101902_bib70","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/138161212800626210","article-title":"Targeting mTOR pathways in human malignancies","volume":"18","author":"Fasolo","year":"2012","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.molmet.2024.101902_bib71","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: one drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab"},{"key":"10.1016\/j.molmet.2024.101902_bib72","series-title":"The mouse in biomedical research","first-page":"623","article-title":"Spontaneous diseases in commonly used mouse strains","author":"Brayton","year":"2007"},{"key":"10.1016\/j.molmet.2024.101902_bib73","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.molmet.2024.101902_bib74","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.molmed.2010.03.003","article-title":"Inflammatory networks during cellular senescence: causes and consequences","volume":"16","author":"Freund","year":"2010","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.molmet.2024.101902_bib75","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.molmet.2024.101902_bib76","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/ncb3225","article-title":"mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype","volume":"17","author":"Herranz","year":"2015","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib77","series-title":"R: a language and environment for statistical computing","year":"2013"},{"key":"10.1016\/j.molmet.2024.101902_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: an R package for omics feature selection and multiple data integration","volume":"13","author":"Rohart","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib79","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"Seaborn: statistical data visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J Open Source Softw"},{"key":"10.1016\/j.molmet.2024.101902_bib80","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"10.1016\/j.molmet.2024.101902_bib81","series-title":"Modeling survival data: extending the Cox model","author":"Therneau","year":"2013"},{"key":"10.1016\/j.molmet.2024.101902_bib82","series-title":"Comparing restricted mean survival time","year":"2023"},{"key":"10.1016\/j.molmet.2024.101902_bib83","first-page":"18","article-title":"Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism","author":"Hahn","year":"2017","journal-title":"Genome Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib84","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/978-1-4939-2550-6_18","article-title":"Step-by-step preparation of proteins for mass spectrometric analysis","volume":"1295","author":"Franz","year":"2015","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.molmet.2024.101902_bib85","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12859-015-0611-3","article-title":"InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams","volume":"16","author":"Heberle","year":"2015","journal-title":"BMC Bioinf"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824000334?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824000334?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:34:52Z","timestamp":1761957292000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877824000334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":87,"alternative-id":["S2212877824000334"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2024.101902","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2024.101902","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"101902"}}