Relative Leukocyte Telomere Length Is Associated with Multimorbidity Burden in Older Adults: Evidence for Sex-Specific Associations

Leukocyte telomere length (LTL) has been proposed as a molecular marker of biological aging reflecting cumulative cellular stress and replicative senescence. Multimorbidity represents a major challenge in aging populations and reflects the progressive accumulation of chronic diseases. However, the relationship between LTL and multimorbidity burden remains incompletely understood. We investigated the association between LTL and multimorbidity burden, assessed using Cumulative Illness Rating Scale (CIRS) indices, in a cohort of older nursing home residents. Sex-stratified analyses were performed to explore potential biological heterogeneity. In multivariate analyses, shorter LTL was significantly associated with higher multimorbidity burden among women, particularly when considering severity- and comorbidity-weighted CIRS indices [False discovery rateadjusted q-values (qFDR < 0.01)], whereas no significant associations were observed in men. Adjustment for functional status partially attenuated but did not eliminate these associations. Organ-specific analyses indicated that these associations in women were primarily driven by cardiovascular, respiratory, gastrointestinal, and genitourinary domains, systems commonly characterized by chronic inflammatory and oxidative stress processes that may promote telomere attrition. Overall, these findings support a sex-specific relationship between telomere dynamics and clinically relevant multimorbidity patterns in very old adults. LTL may reflect biologically meaningful aspects of disease severity and systemic stress regulation rather than merely the accumulation of diagnoses.