{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T03:54:29Z","timestamp":1770522869128,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This research was funded by the Conserjer\u00eda de Educaci\u00f3n de la Junta de Castilla y Le\u00f3n","award":["VA037G19"],"award-info":[{"award-number":["VA037G19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Mitochondrial dysfunction, often reflected by a decline in mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells (PMBCs), is a key hallmark of biological aging and is linked to numerous adverse health outcomes, including frailty and cardiovascular disease. Furthermore, emerging evidence suggests that vitamin D may influence mitochondrial dysfunction. This cross-sectional study aims to investigate the associations of mtDNA-CN with muscular strength, self-rated health, and serum 25-hydroxyvitamin D3 (25(OH)D3) levels in a community-dwelling elderly population. Methods: A total of 149 elderly outpatients (\u226565 years) from Soria, Spain, were included in this cross-sectional study. Muscular strength was assessed using the hand grip strength (HGS) test, and self-rated health-related quality of life (QoL) was measured using the EuroQoL five-dimension questionnaire (EQ-5D). Genomic DNA was extracted from peripheral blood, and mtDNA-CN was quantified using quantitative real-time PCR (qPCR). Serum 25(OH)D3, intact parathyroid hormone (iPTH), phosphorus, calcium, albumin and other mineral metabolism markers were measured. Statistical analyses, including Spearman correlations and multivariate logistic regression, were performed to assess associations, with stratification by sex. Results: In the total population, a marginally significant positive correlation was observed between mtDNA copy number (mtDNA-CN) and serum 25(OH)D3 levels (r = 0.210; p = 0.010), which did not remain significant after Bonferroni correction. Among women, lower mtDNA-CN was significantly linked to muscle weakness (p = 0.005), mobility problems (p = 0.009), and a trend toward self-care difficulties (p = 0.016). Multivariate analysis confirmed an independent association with increased mobility impairment risk (adjusted OR = 0.983; 95% CI: 0.97\u20131.00; p = 0.009). No significant associations were observed between mtDNA-CN and dynapenia or QoL components in the male group. Conclusions: This study identified a marginally significant positive correlation between serum 25(OH)D3 levels and mtDNA-CN in the total population (r = 0.210; p = 0.010), which did not persist after Bonferroni correction, suggesting an exploratory link between vitamin D status and mitochondrial homeostasis in older adults. In addition, these results highlight sex-specific differences in mtDNA-CN as a potential biomarker of functional decline, particularly of mobility, in women. These findings support the idea that mtDNA-CN could serve as an integrated biomarker and that sex-specific nutrition could be used to promote healthy aging.<\/jats:p>","DOI":"10.3390\/nu18030526","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:55:11Z","timestamp":1770216911000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex Disparities in the Processes Underlying Aging: Mitochondrial DNA Copy Number Associations with Dynapenia, 25-Hydroxyvitamin D3 Levels and Quality of Life in Older Adults"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-7672","authenticated-orcid":false,"given":"Zoraida","family":"Verde","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"},{"name":"Grupo Investigaci\u00f3n Reconocida (GIR) Farmacogen\u00e9tica, Gen\u00e9tica del C\u00e1ncer, Polimorfismos Gen\u00e9ticos y Farmacoepidemiolog\u00eda, University of Valladolid, 47005 Valladolid, Spain"},{"name":"Unidad de Investigaci\u00f3n Consolidada (UIC) de Castilla y Le\u00f3n 387, University of Valladolid, 42004 Soria, Spain"},{"name":"Centro de Estudios Gregorio Mara\u00f1\u00f3n, Fundaci\u00f3n Ortega-Mara\u00f1\u00f3n, 28010 Madrid, Spain"}]},{"given":"Sara","family":"Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biomedicine and Theranostics (LBioMiT), CNC\u2014UC-Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute of Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4290-9004","authenticated-orcid":false,"given":"Isabel","family":"Erenas-Ondategui","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-491X","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biomedicine and Theranostics (LBioMiT), CNC\u2014UC-Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"FMUC\u2014Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8662-1435","authenticated-orcid":false,"given":"Celia","family":"Chicharro Miguel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"},{"name":"Centro de Estudios Gregorio Mara\u00f1\u00f3n, Fundaci\u00f3n Ortega-Mara\u00f1\u00f3n, 28010 Madrid, Spain"}]},{"given":"Sandra","family":"Estepa Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"}]},{"given":"Claudia","family":"Ollauri-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"},{"name":"Unidad de Investigaci\u00f3n Consolidada (UIC) de Castilla y Le\u00f3n 387, University of Valladolid, 42004 Soria, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-8161","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Oliveiros","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Group of Environmental Genetics of Oncobiology (CIMAGO), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5324-1014","authenticated-orcid":false,"given":"Ana","family":"Fern\u00e1ndez-Araque","sequence":"additional","affiliation":[{"name":"Grupo Investigaci\u00f3n Reconocida (GIR) Farmacogen\u00e9tica, Gen\u00e9tica del C\u00e1ncer, Polimorfismos Gen\u00e9ticos y Farmacoepidemiolog\u00eda, University of Valladolid, 47005 Valladolid, Spain"},{"name":"Unidad de Investigaci\u00f3n Consolidada (UIC) de Castilla y Le\u00f3n 387, University of Valladolid, 42004 Soria, Spain"},{"name":"Department of Nursery, Universidad de Valladolid, Campus Duques de Soria, 42004 Soria, Spain"}]},{"given":"Manuela","family":"Grazina","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biomedicine and Theranostics (LBioMiT), CNC\u2014UC-Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"FMUC\u2014Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","unstructured":"Chand, S. 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