Telomere length (TL) and DNA methylation–based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL (LTL; measured by qPCR [n = 635] or flow FISH [n = 144]) and five epigenetic clocks (Hannum, DNAmAge pan-tissue, PhenoAge, SkinBlood, or GrimAge clocks), or their epigenetic age acceleration measures in healthy adults (age 19–61 years). LTL showed statistically significant negative correlations with all clocks (qPCR: r = − 0.26 to − 0.32; flow FISH: r = − 0.34 to − 0.49; p 0.05 for both). In conclusion, the relationships between LTL and epigenetic clocks were limited to clocks reflecting phenotypic age. The observed association between LTL and EEAA reflects the ability of both measures to detect immunosenescence. The observed modest correlations between LTL and epigenetic clocks highlight a possible benefit from incorporating both measures in understanding disease etiology and prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00586-4.
