{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:59:01Z","timestamp":1776416341152,"version":"3.51.2"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":92,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-178123"],"award-info":[{"award-number":["PJT-178123"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Queen\u2032s Research Initiation"},{"name":"Canada Research Chair in Brain Resilience","award":["CRC 2023-00155"],"award-info":[{"award-number":["CRC 2023-00155"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The progressive accumulation of physiological stress as we age, known as allostatic load, is linked to an increased risk of dementia. Fostering brain resilience through physical exercise can counteract allostatic load and improve adaptation to age-related brain alterations. Fibronectin type III domain-containing protein 5 (FNDC5)\/irisin is a neuroprotective exercise-linked hormone found in extracellular vesicles (EV-FNDC5\/irisin). Here, we sought to analyse EV-FNDC5\/irisin in ageing as a promising biomarker of brain resilience.<\/jats:p>\n                  <jats:p>We measured exercise-associated factors, including EV-FNDC5\/irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B in the serum of 31 young (18\u201328 years) and 19 older subjects (65\u201379 years).<\/jats:p>\n                  <jats:p>Levels of FNDC5\/irisin in serum-derived EVs are markedly reduced in older subjects compared to young (P = 0.004). We report a reduction in nanoparticles isolated from the serum of older participants (P = 0.009). While EV-FNDC5\/irisin positively correlates with BDNF in young subjects (Spearman r = 0.40, P = 0.038), this correlation is absent in elderly subjects (Spearman r = \u22120.25, P = 0.34).<\/jats:p>\n                  <jats:p>This study provides initial evidence that EV-FNDC5\/irisin is reduced in older individuals and loses correlation with BDNF. Our identification of peripheral, exercise-linked factors associated with age may inform biomarker discovery and interventions to promote brain resilience.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag085","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:46:35Z","timestamp":1775130395000},"source":"Crossref","is-referenced-by-count":0,"title":["Fibronectin type III domain-containing protein 5\/irisin in extracellular vesicles is reduced in older individuals"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4816-9457","authenticated-orcid":false,"given":"Tai R","family":"Hunter","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia M","family":"Lyra E Silva","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]},{"name":"Centre for Neuroscience Studies, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilherme B","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayna","family":"Rody","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Cidade Universit\u00e1ria , Rio de Janeiro, RJ 21941-902 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-733X","authenticated-orcid":false,"given":"Luis E","family":"Santos","sequence":"additional","affiliation":[{"name":"D\u2019OR Institute for Research and Education, Rua Diniz Cordeiro , Rio de Janeiro, RJ 22281-100 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Bullock","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University , Hamilton, ON L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, ON M5S 1A8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheela","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University , Hamilton, ON L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimee J","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University , Hamilton, ON L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer J","family":"Heisz","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University , Hamilton, ON L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Fahnestock","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, ON L8N 3K7 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8358-0589","authenticated-orcid":false,"given":"Fernanda G","family":"De Felice","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]},{"name":"Centre for Neuroscience Studies, Queen\u2019s University , Kingston, ON K7L 2V5 ,","place":["Canada"]},{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Cidade Universit\u00e1ria , Rio de Janeiro, RJ 21941-902 ,","place":["Brazil"]},{"name":"D\u2019OR Institute for Research and Education, Rua Diniz Cordeiro , 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