{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:26:10Z","timestamp":1787336770865,"version":"build-2736575974"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Special Nursing Project of Jinling Hospital","award":["2023YYHLZX175"],"award-info":[{"award-number":["2023YYHLZX175"]}]},{"name":"The Science and Technology Innovation Research Program of Jinling Hospital","award":["2023JCYJZD078"],"award-info":[{"award-number":["2023JCYJZD078"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Age-related molecular trajectories of metabolic dysfunction-associated steatotic liver disease (MASLD) remain insufficiently characterized, limiting age-stratified risk assessment and intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To test whether MASLD-related molecular changes with age merely reflect accelerated physiological aging or represent a disease-specific divergence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized public transcriptomic data from normal liver and MASLD samples to identify differential transcriptomic signals. We employed Spearman correlation analysis and generalized additive models (GAM) for nonlinear age-related trajectory modeling, and functional enrichment analysis for signaling pathway characterization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We integrated 1,354 public liver transcriptome samples from GEO and GTEx databases to construct a cross-age cohort. Differential expression and age-correlation analyses showed minimal overlap (only 22 genes) between age-associated genes in MASLD and controls, with some genes displaying opposite age-related trends. GAM identified four major expression patterns in MASLD\u2014stable, early-life change, late-life acceleration, and mid-life fluctuation\u2014with trajectory inflection time points around ages ~35 and ~75. Functional enrichment indicated that control age-associated genes mainly involved classical cell cycle processes, whereas MASLD changes were enriched for protein deubiquitination, proteostasis imbalance, and p53-related stress and apoptotic signaling. Many MASLD age-associated genes were also associated with fibrosis stage or NAS, largely in concordant directions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MASLD exhibits disease-specific age-related transcriptional remodeling characterized by dysregulation of proteostasis and deubiquitination pathways, activation of cellular stress-response programs, and enrichment of p53-associated apoptotic signaling, rather than a simple acceleration of physiological aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356820","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:29:56Z","timestamp":1787333396000},"page":"e0356820","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated liver transcriptomic data reveal differences in aging-associated regulation between metabolic dysfunction-associated steatotic liver disease and normal liver 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