Table 2.

Multivariable regression for the association between epigenetic clocks or age acceleration measures and leukocyte telomere length

	Flow FISH total lymphocyte TL (N = 144)		qPCR TL (N = 635)
	β1	p-value	β1	p-value
Epigenetic age clocks2
GrimAge	− 0.61	0.003	− 0.35	< 0.0001
PhenoAge	− 0.57	< 0.0001	− 0.28	< 0.0001
Hannum	− 0.49	0.0006	− 0.26	0.0004
SkinBlood	− 0.26	0.36	− 0.11	0.42
DNAmAge	− 0.35	0.06	− 0.14	0.09
Epigenetic age acceleration measures3
AAR GrimAge	− 0.32	0.003	− 0.18	< 0.0001
AAR PhenoAge	− 0.39	< 0.0001	− 0.19	< 0.0001
AAR Hannum	− 0.24	0.0009	− 0.14	0.0004
AAR SkinBlood	− 0.07	0.37	− 0.03	0.42
AAR DNAmAge	− 0.17	0.06	− 0.07	0.09
IEAA DNAmAge	− 0.11	0.18	− 0.03	0.52
EEAA DNAmAge	− 0.32	< 0.0001	− 0.18	< 0.0001

DNA for qPCR telomere length or methylationEpic array was extracted from peripheral blood mononuclear cells (PBMCs; n = 219) or frozen whole blood (n = 416). Flow FISH telomere length was measured in a subset with cryopreserved PBMC samples (n = 144)

Flow FISH fluorescence in situ hybridization (FISH) with flow cytometry, qPCR quantitative polymerase chain reaction, TL telomere length, AAR age acceleration residual, IEAA intrinsic epigenetic age acceleration, EEAA extrinsic epigenetic age acceleration

¹All measures are in z-scores; β is interpreted as standard deviation (SD) change in epigenetic age clock or age acceleration measure under-study with each SD of TL; models were adjusted for chronological age, sex, and race

²Epigenetic clocks were developed using penalized regression to select CpG sites that produce the most accurate estimate of chronological age only (for DNAmAge, Hannum, and SkinBlood clocks), or to predict mortality risk from a combination of phenotypic indicators, including chronological age and blood chemistries (PhenoAge), or selected blood proteins and smoking history, controlling for chronological age (GrimAge)

³All age acceleration models used age-adjusted TL and were adjusted for sex and race