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.
This study identified a marginally significant positive correlation between serum 25(OH)D3 levels and mtDNA-CN in older adults (r = 0.210; p = 0.010), which did not persist after Bonferroni correction, and found sex-specific associations whereby lower mtDNA-CN was linked to muscle weakness, mobility problems, and self-care difficulties in women but not men.
Key Findings
Results
A marginally significant positive correlation was observed between mtDNA copy number and serum 25-hydroxyvitamin D3 levels in the total population.
The correlation coefficient was r = 0.210 with p = 0.010 in the total population of 149 elderly outpatients.
This correlation did not remain significant after Bonferroni correction.
The association was described as an 'exploratory link between vitamin D status and mitochondrial homeostasis in older adults.'
Participants were community-dwelling elderly outpatients aged ≥65 years from Soria, Spain.
Results
Lower mtDNA copy number was significantly associated with muscle weakness in women.
The association between lower mtDNA-CN and muscle weakness in women was statistically significant (p = 0.005).
No significant association between mtDNA-CN and dynapenia was observed in the male group.
Muscular strength was assessed using the hand grip strength (HGS) test.
The study design was cross-sectional with stratification by sex.
Results
Lower mtDNA copy number was significantly linked to mobility problems in women.
The association between lower mtDNA-CN and mobility problems in women reached statistical significance at p = 0.009.
Multivariate logistic regression confirmed an independent association with increased mobility impairment risk (adjusted OR = 0.983; 95% CI: 0.97–1.00; p = 0.009).
Quality of life was measured using the EuroQoL five-dimension questionnaire (EQ-5D).
No significant associations were observed between mtDNA-CN and QoL components in the male group.
Results
Lower mtDNA copy number showed a trend toward association with self-care difficulties in women.
The association between lower mtDNA-CN and self-care difficulties in women showed a trend at p = 0.016.
This was described as a 'trend toward self-care difficulties' rather than a fully significant finding.
The association was observed exclusively in women, with no corresponding finding in men.
Self-care was assessed as one of the five dimensions of the EQ-5D questionnaire.
Methods
The study population consisted of 149 elderly outpatients aged 65 years or older from Soria, Spain.
Participants were community-dwelling elderly outpatients.
The study was cross-sectional in design.
Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs), 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 included Spearman correlations and multivariate logistic regression with stratification by sex.
Conclusions
Sex-specific differences in mtDNA copy number were identified as a potential biomarker of functional decline, particularly mobility, in women but not men.
No significant associations were observed between mtDNA-CN and dynapenia or any QoL components in men.
The authors conclude that 'mtDNA-CN could serve as an integrated biomarker and that sex-specific nutrition could be used to promote healthy aging.'
The findings highlight that biological aging processes, as reflected by mtDNA-CN, may differ between sexes in older adults.
The results support sex-stratified approaches when using mtDNA-CN as a biomarker of aging-related functional decline.
Verde Z, Martins S, Erenas-Ondategui I, Santos M, Chicharro Miguel C, Estepa Hernández S, et al.. (2026). 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.. Nutrients. https://doi.org/10.3390/nu18030526