Aging & Longevity

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.

TL;DR

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

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.

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.

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.

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.

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.

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.

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Citation

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