{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:16:14Z","timestamp":1788239774096,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19 AG023122"],"award-info":[{"award-number":["U19 AG023122"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG024824"],"award-info":[{"award-number":["AG024824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["U19 AG023122"],"award-info":[{"award-number":["U19 AG023122"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AG024824"],"award-info":[{"award-number":["AG024824"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02ebg5q27","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Objective: Despite most often used in research and medicine, it is unclear how well blood metabolite levels can reflect metabolic changes in tissues. Methods: We used untargeted metabolomic data from plasma, liver, gastrocnemius muscle, kidney, inguinal fat, and gonadal fat tissues from mice treated with lifespan-extending interventions: caloric restriction, rapamycin, canagliflozin, 17-\u03b1 estradiol, and acarbose. Results: For each tissue, about 37% of the identified metabolites were also found in plasma and used for comparative analyses. We found that plasma metabolites do not primarily reflect the metabolome of a single tissue type. Caloric restriction caused the highest proportion of significantly altered metabolites detected in both organs and blood. Unsaturated triacylglycerols, diacylglycerols, amino acid-derivatives, and sphingomyelins had the most concordant overlaps between four tissues and plasma, followed by carbohydrates with three tissue\/plasma intersections. Concordant plasma\/tissue changes were found more pronounced in male mice than in female mice. Surprisingly, many compounds that responded similarly to lifespan-extending treatments in tissues and in plasma originated from dietary compounds, specifically, ergothioneine, DHA-containing fats, and diacylglycerides. Ergothioneine, previously associated with healthy aging in humans, showed concordant treatment responses in blood and all tissues except gonadal fat. DHA-containing fats showed consistent regulation between blood and inguinal and gonadal adipose tissue. The kidneys showed coherent trends with blood metabolite levels for LPC 15:0, LPC 17:0, and pinitol. Under treatments with strong life-extending effects, 1,5-anhydro-glucitol blood levels were co-regulated with both liver and kidney levels. Conclusions: Overall, plasma can only serve as limited proxy for tissue metabolism. Yet, several potential blood biomarkers were discovered as concordant in plasma and tissues in lifespan-extending interventions.<\/jats:p>","DOI":"10.3390\/metabo16090609","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma as Proxy for Tissue Metabolism When Extending Lifespan in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5232-6980","authenticated-orcid":false,"given":"Sara","family":"Greenfield","sequence":"first","affiliation":[{"name":"West Coast Metabolomics Center, University of California Davis, Davis, CA 95618, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"C. Titus","family":"Brown","sequence":"additional","affiliation":[{"name":"Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA 95618, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-8928","authenticated-orcid":false,"given":"Oliver","family":"Fiehn","sequence":"additional","affiliation":[{"name":"West Coast Metabolomics Center, University of California Davis, Davis, CA 95618, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/ansa.202300011","article-title":"Blood microsampling technologies: Innovations and applications in 2022","volume":"4","author":"Thangavelu","year":"2023","journal-title":"Anal. 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