Sex-specific variation in telomere length and its links to physiological aging, aerobic capacity, and vascular function: A cross-sectional analysis

Background: Telomeres are specialized DNA complexes at the end of chromosomes that protect DNA and preserve the genome during replication. Longer leukocyte telomere length (LTL) is associated with longevity and resistance to cardiovascular disease (CVD). Shorter telomere length has been linked to non-traditional risk factors such as vascular aging (i.e., endothelial dysfunction, increased intima-media thickness [IMT]), and aerobic capacity (VO 2 max). Additionally, previous findings suggest sex differences in LTL, with women having longer telomeres than men, in part explained by sex chromosomes and hormones. Additionally, sex hormones have beneficial effects on these non-traditional CVD risk factors; thus, variables such as sex, hormones, and aging are important factors to consider when examining the associations between telomere length and non-traditional CVD risk factors. Therefore, we sought to investigate the associations of LTL with endothelial function, IMT, and VO 2 max while considering both chronological and gonadal aging. Methods: Participants were 65 healthy women and 67 healthy eugonadal men. Women were classified by ovarian age as premenopausal (n=19, 30±6y; mean±SD), perimenopausal (n=23, 53±2y), and postmenopausal (n=23, 57±6y). Men were classified as young (n=20, 30±4y) and middle-aged/older (MA/O) (MA/O; n=47, 61±7y). Endothelial function was assessed by brachial artery flow-mediated dilation (FMD), and IMT was measured by carotid artery ultrasound. VO 2 max was also measured in each participant. LTL was measured from genomic DNA isolated from peripheral blood mononuclear cells using quantitative real-time polymerase chain reaction. An unpaired Welch’s two-tailed t-test was used to determine differences between groups, and Spearman correlations were performed between LTL and other continuous variables of interest (FMD, IMT, & VO 2 max). Results: Women had longer LTL than men (p=0.03), but this difference was limited to those over age 50, where women showed longer LTL than age-matched men (p=0.03). In contrast, premenopausal women did not differ from their age-matched males (p >0.05). Women overall had a higher FMD (p< 0.0001) and lower IMT (p=0.004) than men. However, when including only postmenopausal women and MA/O men in the analysis, both FMD & IMT did not differ by sex (p >0.05). LTL was positively correlated with FMD (pooled r=0.20, p=0.03), driven by positive associations in women (r=0.23, p=0.08), and not men (r=0.07, p=0.57). LTL was negatively correlated with IMT (pooled r=-0.30, p=0.002), also driven by associations in women (r=-0.33, p=0.01) and not men (r=-0.17, p=0.17). VO 2 max was not correlated with LTL (pooled r=0.07, p=0.46; young, pooled r=0.2., p=0.24; > age 50 pooled r=-0.13, p=0.2)). Interestingly, though, when analyzing LTL correlations with VO 2 max by age and sex, we saw LTL was strongly correlated in premenopausal women (r=0.53, p=0.02), but not young men (r=0.06, p=0.80). Conclusion: Overall, the findings from this retrospective cross-sectional analysis reveal a pattern in which women’s vascular health, cardiorespiratory fitness, and telomeres influence each other greater than those of men. This highlights that the mechanisms linking cardiovascular function and cellular aging operate differently between sexes and across the life span. Support: NIH T32 AG000279 (MNK, LED), R01 AG089069 (KLM), R56AG072094 (KLM), F32AG071273 (LED) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.