Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort.
BACKGROUND
Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality.


RESULTS
DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δage (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10-1.38) for all-cause mortality, 1.22 (95 % CI 1.03-1.45) for cancer mortality, and 1.19 (95 % CI 0.98-1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Δage calculated using the epigenetic clock developed by Hannum.


CONCLUSIONS
These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.
Laura
L
Perna
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.
Yan
Y
Zhang
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.
Ute
U
Mons
Saarland Cancer Registry, Präsident Baltz Straße 5, 66119 Saarbrücken, Germany.
Bernd
B
Holleczek
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany.
Kai-Uwe
KU
Saum
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany ; Network Aging Research (NAR), University of Heidelberg, Bergheimer Straße 20, 69115 Heidelberg, Germany.
Hermann
H
Brenner
D000368:Aged; D000375:Aging / Q000235:genetics*; D001769:Blood / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics*; D002423:Cause of Death; D015331:Cohort Studies; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors
DNA methylation age; Epigenetic age acceleration; Epigenetic clock; Mortality risk