Telomere length and epigenetic clocks as markers of cellular aging: a comparative study.
Level 4 - case-series / case-control
Cross-sectional observational study evaluating biomarker correlations
PubMed 35585300 · doi:10.1007/s11357-022-00586-4
What was done
Multivariable regression models evaluated the relationship between leukocyte telomere length (LTL; measured by qPCR [n = 635] or flow FISH [n = 144]) and five DNA methylation epigenetic clocks (Hannum, pan-tissue DNAmAge, PhenoAge, SkinBlood, and GrimAge) as well as measures of epigenetic age acceleration in healthy adults aged 19–61 years. Models were adjusted for age, sex, and race.
What was found
Unadjusted LTL showed negative correlations across all five clocks (qPCR: r = -0.26 to -0.32; flow FISH: r = -0.34 to -0.49; p < 0.001 for all). After adjustment for age, sex, and race, significant associations remained only for PhenoAge, GrimAge, and Hannum clocks (p < 0.01 for flow FISH; p < 0.001 for qPCR), as well as their respective age acceleration measures (p < 0.01 for all). LTL was significantly associated with extrinsic epigenetic age acceleration (EEAA; p < 0.0001 for both qPCR and flow FISH), but not intrinsic epigenetic age acceleration (IEAA; p > 0.05 for both).
Why it matters
The findings indicate that telomere attrition and epigenetic clocks capture distinct biological aging mechanisms, with overlap largely restricted to clocks that capture immune system remodeling and phenotypic aging.
Limits
The cross-sectional design cannot establish temporal or causal relationships between telomere attrition and epigenetic changes. Findings in healthy 19–61 year olds may not generalize to older individuals or populations with chronic clinical conditions. Flow FISH measurements were available in only a subset of participants (n = 144).
Cited by
- supports The Hannum epigenetic clock incorporates blood cell composition measures, enabling it to capture inflammation signals more effectively than the original Horvath pan-tissue clock.