Association of leukocyte telomere length with perceived physical fatigability

Background: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age. Methods: Two generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60–108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years later using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0–50, higher scores = greater fatigability). Generalized estimating equations were generated to model the association between LTL and PFS Physical scores. Results: Prevalence of greater physical fatigability (PFS scores≥15) was 41.9 %. Using generalized estimating equations, a one kilobase pair shorter LTL was associated with higher PFS Physical scores (β = 1.8, p <.0001), accounting for family structure, and adjusting for field center, follow-up time, sex, and follow-up body mass index, physical activity, and chronic health conditions. When age was included as a covariate, the association was fully attenuated (β = 0.1, p =.78). Conclusion: LTL may provide an alternative method for estimating an individual's lifetime exposure to chronic stressors, but does not appear to provide additional information not captured by chronological age. Further research is needed to characterize the interaction between age, LTL, and perceived fatigability, and develop a method of identifying individuals at risk for deleterious aging.