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 < 0.001 for all). Yet, models adjusted for age, sex, and race revealed significant associations between three of five clocks (PhenoAge, GrimAge, and Hannum clocks) and LTL by flow FISH (p < 0.01 for all) or qPCR (p < 0.001 for all). Significant associations between age acceleration measures for the same three clocks and qPCR or flow FISH TL were also found (p < 0.01 for all). Additionally, LTL (by qPCR or flow FISH) showed significant associations with extrinsic epigenetic age acceleration (EEAA: p < 0.0001 for both), but not intrinsic epigenetic age acceleration (IEAA; 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.

端粒长度 (TL) 和基于 DNA 甲基化的表观遗传时钟是生物学年龄的标志，但两者之间的关系尚不完全清楚。在这里，我们使用多变量回归模型来评估白细胞 TL（LTL；通过 qPCR [ n  = 635] 或流 FISH [ n  = 144] 测量）和五个表观遗传时钟（Hannum、DNAmAge pan-tissue、PhenoAge、SkinBlood、或 GrimAge 时钟），或其在健康成年人（19-61 岁）中的表观遗传年龄加速测量。LTL 与所有时钟显示出统计学上显着的负相关（qPCR：r  = - 0.26 至 - 0.32；流 FISH：r  = - 0.34 至 - 0.49；p < 0.001 全部）。然而，根据年龄、性别和种族调整的模型显示，五个时钟中的三个（PhenoAge、GrimAge 和 Hannum 时钟）与流 FISH（所有p  < 0.01）或 qPCR（所有p  < 0.001）的 LTL 之间存在显着关联。还发现了相同三个时钟的年龄加速测量与 qPCR 或流 FISH TL 之间的显着关联（所有p  < 0.01）。此外，LTL（通过 qPCR 或流式 FISH）显示与外在表观遗传年龄加速（EEAA：p  < 0.0001 两者）显着相关，但与内在表观遗传年龄加速无关（IEAA；p > 0.05 两者）。总之，LTL 和表观遗传时钟之间的关系仅限于反映表型年龄的时钟。观察到的 LTL 和 EEAA 之间的关联反映了两种测量方法检测免疫衰老的能力。观察到的 LTL 和表观遗传时钟之间的适度相关性突出了将这两种措施纳入了解疾病病因和预后的可能益处。