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Chronic low-grade inflammation has been proposed as a key pathophysiological mechanism underlying physical frailty, although its role in cognitive frailty remains undefined. In this cross-sectional study, we assessed the relationship between frailty status, both physical and cognitive, and plasma concentrations of six inflammatory biomarkers\u2014C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-\u03b1), soluble TNF-\u03b1 receptor type II (sTNF-RII), high-temperature requirement serine protease A1 (HTRA1), and growth differentiation factor 15 (GDF15)\u2014in a cohort of Spanish older adults (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009150,\u2009\u2265\u200965\u00a0years old), classified according to Fried\u2019s frailty phenotype and frailty index. The results showed notable differences between frailty phenotype and frailty index, and highlighted CRP, TNF-\u03b1, sTNF-RII, and GDF15 as key biomarkers significantly associated with physical frailty status, with CRP and TNF-\u03b1 also discriminating pre-frail individuals. sTNF-RII stood out for its high predictive capacity, while GDF15 added value as an indicator of sustained cellular stress. Regarding cognitive frailty, CRP, TNF-\u03b1, and GDF15 displayed significant associations with this condition. sTNF-RII and HTRA1, scarcely studied in this context, showed promising and significant associations (specific for cognitive frailty in the case of HTRA1) that justify their inclusion in future research aimed at better understanding the inflammatory mechanisms involved in cognitive frailty.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01931-z","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T21:03:02Z","timestamp":1760648582000},"page":"2063-2084","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association of inflammatory biomarkers with physical and cognitive frailty in a Spanish population of older adults"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0826-7343","authenticated-orcid":false,"given":"Carlota","family":"Lema-Arranz","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8557-538X","authenticated-orcid":false,"given":"Ali","family":"Hemadeh","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7537-3977","authenticated-orcid":false,"given":"Natalia","family":"Fern\u00e1ndez-Bert\u00f3lez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-8531","authenticated-orcid":false,"given":"Nuria","family":"Cibeira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-2354","authenticated-orcid":false,"given":"Roc\u00edo","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-1966","authenticated-orcid":false,"given":"Solange","family":"Costa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-8960","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Mill\u00e1n-Calenti","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-6515","authenticated-orcid":false,"given":"Laura","family":"Lorenzo-L\u00f3pez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5572-1089","authenticated-orcid":false,"given":"Vanessa","family":"Valdiglesias","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7649-2599","authenticated-orcid":false,"given":"Blanca","family":"Laffon","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"1931_CR1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.jamda.2015.12.016","volume":"17","author":"M Cesari","year":"2016","unstructured":"Cesari M, Prince M, Thiyagarajan JA, et al. 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