{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:20:00Z","timestamp":1787746800746,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["FPU23\/01973"],"award-info":[{"award-number":["FPU23\/01973"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01355"],"award-info":[{"award-number":["PI19\/01355"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01905"],"award-info":[{"award-number":["PI22\/01905"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FORT23\u201000026"],"award-info":[{"award-number":["FORT23\u201000026"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS24\/00153"],"award-info":[{"award-number":["DTS24\/00153"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n The molecular mechanisms underlying frailty are under intense investigation. Independent observational studies revealed various biological processes and biomarkers differentially expressed in frail individuals and after interventions. Recently, several transcriptomic approaches have described molecular patterns associated with frailty status. However, the effects of physical exercise interventions remain unexplored. Two studies (FRAILOMIC and BIOFRAIL) identified molecular signatures associated with frailty. The objective of the study was to analyse the expression of the FRAILOMIC and BIOFRAIL biomarkers following a multicomponent personalized exercise intervention in older adults.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A multi\u2010centre study included a control (\n n<\/jats:italic>\n \u2009=\u200924, with 14 women and 10 men, median age 80\u2009\u00b1\u20095) and an exercise intervention group (\n n<\/jats:italic>\n \u2009=\u200944, with 38 women and 6 men, median age 79\u2009\u00b1\u20094). The latter underwent a 16\u2010week multicomponent presential physical exercise programme; clinical, functional and frailty assessments were performed before and after the intervention in both groups. Latent class analysis identified \u2018responders\u2019 and \u2018non\u2010responders\u2019 to the intervention. Data in a testosterone\u2010suppressed control cohort of older men with prostatic cancer receiving androgen deprivation therapy (\n n<\/jats:italic>\n \u2009=\u200921) were included. Molecular biomarkers were measured via qRT\u2010PCR and ELISA.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The exercise group presented improvements in functional capacity, as shown by Short Physical Performance Battery (SPPB) (post\u2010 10.1 vs. 9.1 in pre\u2010intervention), grip strength (18.3 vs. 16.9\u2009kg), gait speed (0.85 vs. 0.78\u2009m\/s), sarcopenia (2.1 vs. 3.0) and frailty status by Fried Frailty Phenotype (1.6 vs 2.1 criteria) (all \u2264\u20090.004). ANCOVA revealed significant improvements in SPPB (\n p<\/jats:italic>\n \u2009=\u20090.04) and grip strength (\n p<\/jats:italic>\n \u2009<\u20090.005) with exercise. Four of the six FRAILOMIC biomarkers (\n miR125b<\/jats:italic>\n ,\n miR194<\/jats:italic>\n ,\n RAGE<\/jats:italic>\n and Troponin) and six of seven BIOFRAIL biomarkers (\n EGR1<\/jats:italic>\n ,\n CXCL8<\/jats:italic>\n ,\n GOS2<\/jats:italic>\n ,\n NSF<\/jats:italic>\n ,\n DDX11L1<\/jats:italic>\n and\n miR454<\/jats:italic>\n ) reversed significantly their expression after exercise training (\n p<\/jats:italic>\n \u2009\u2264\u20090.05 for FRAIOLMIC and \u2264\u20090.01 for BIOFRAIL respectively). In contrast, these changes were not observed in testosterone\u2010suppressed controls, who experienced muscle loss. Latent class analysis revealed 36 \u2018responders\u2019 (with 32 cases from intervention group) and 29 \u2018non\u2010responders\u2019. Logistic regression showed that\n miR454<\/jats:italic>\n , EGR1,\n DDX11L1<\/jats:italic>\n and Troponin displayed the strongest predictive value in distinguishing responders from non\u2010responders.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Exercise intervention improved functional status and reversed biological frailty, as evidenced by changes in multiple MultiOMIC frailty biomarkers. Among these, the BIOFRAIL trio\u2014\n miR454<\/jats:italic>\n ,\n EGR1<\/jats:italic>\n and\n DDX11L1<\/jats:italic>\n \u2014showed the strongest predictive power for intervention response with AUC of 0.83. This study provides proof\u2010of\u2010concept for the utility of OMIC\u2010derived frailty biomarkers as outcome measures after intervention.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70362","type":"journal-article","created":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T22:54:47Z","timestamp":1786316087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Supervised Exercise Intervention Restores Physical Activity and MultiOMIC\u2010Derived Frailty Biomarkers in Older Adults"],"prefix":"10.1002","volume":"17","author":[{"given":"Diego","family":"Marcos\u2010Perez","sequence":"first","affiliation":[{"name":"Cellular Oncology Group Biogipuzkoa (Biodonostia) Health Research Institute San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cruces\u2010Salguero","sequence":"additional","affiliation":[{"name":"Cellular Oncology Group Biogipuzkoa (Biodonostia) 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