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We pooled data from seven randomized CR trials (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009829) and examined randomization to CR and change in weight with a biomarker index composed of CRP, IL-6, cystatin C, insulin, GDF-15, and TNF-R1. CR improved the composite biomarker index. The effect of CR decreased from \u22122.2 to \u22121.2 (95% CI \u22122.0 to \u22120.3) after adjustment for weight, while the effect of weight loss decreased from 0.22 to 0.16 (95% CI 0.09 to 0.23) when CR was included in the model, suggesting improvements in the biomarker index are only partially mediated by the amount of weight loss. Mediation analyses showed that only 48.5% (95% CI 22.6 to 82.2%) of the CR effects were explained by weight loss. These findings support the potential for composite biomarker indices as measures of intervention response and CR as a strategy to target biological aging.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02529-9","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:48:53Z","timestamp":1789184933000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of caloric restriction on biological aging: insights from a composite biomarker index in older adults"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3891-8592","authenticated-orcid":false,"given":"Cassidy A.","family":"Guida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Chi","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Neiberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Semelka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise K.","family":"Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Nicklas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Kritchevsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2529_CR1","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C L\u00f3pez-Ot\u00edn","year":"2013","unstructured":"L\u00f3pez-Ot\u00edn C, et al. 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