{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:49:39Z","timestamp":1787636979168,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002911","name":"Complutense University Research Group","doi-asserted-by":"publisher","award":["910379"],"award-info":[{"award-number":["910379"]}],"id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer\u2019s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression.<\/jats:p>","DOI":"10.3390\/biom16030475","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:07:06Z","timestamp":1774271226000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peripheral Oxidation-Inflammation and Immunosenescence in Triple-Transgenic Mice for Alzheimer\u2019s Disease (3xTg-AD) at Early Neuropathological Stages of Disease and Decrease of Immune Impairment by Voluntary Exercise"],"prefix":"10.3390","volume":"16","author":[{"given":"M\u00f3nica","family":"De la Fuente","sequence":"first","affiliation":[{"name":"Department of Genetics, Physiology and Microbiology (Animal Physiology Unit), Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Investigation Hospital 12 Octubre (i+12), 28041 Madrid, Spain"},{"name":"Nanocaging Research Group, Department of Biosciences, School of Biomedical and Health Sciences, Universidad Europea de Madrid, Villaviciosa de Od\u00f3n, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-3330","authenticated-orcid":false,"given":"Antonio","family":"Garrido","sequence":"additional","affiliation":[{"name":"Institute of Investigation Hospital 12 Octubre (i+12), 28041 Madrid, Spain"},{"name":"Nanocaging Research Group, Department of Biosciences, School of Biomedical and Health Sciences, Universidad Europea de Madrid, Villaviciosa de Od\u00f3n, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Vida","sequence":"additional","affiliation":[{"name":"Department of Genetics, Physiology and Microbiology (Animal Physiology Unit), Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashed","family":"Manassra","sequence":"additional","affiliation":[{"name":"Department of Genetics, Physiology and Microbiology (Animal Physiology Unit), Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-489X","authenticated-orcid":false,"given":"Lydia","family":"Gimenez-Llort","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Universitat Aut\u00f2noma de Barcelona, Campus Bellaterra, 08193 Barcelona, Spain"},{"name":"Department of Psychiatry and Forensic Medicine, Medicine School, Universitat Aut\u00f2noma de Barcelona, Campus Bellaterra, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.2174\/138161209789058110","article-title":"An update of the oxidation-inflammation theory of aging: The involvement of the immune system in oxi-inflamm-aging","volume":"15","author":"Miquel","year":"2009","journal-title":"Curr. 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