表观遗传时钟已成为衡量生物年龄和潜在死亡率预测指标的新指标。我们的目的是测试使用不同的表观遗传时钟估计的表观遗传年龄加速(EAA)是否可以预测长期的整体,心血管或癌症死亡率。
■我们分析了1999-2002年国家健康和营养检查调查的2,105名参与者的数据,年龄≥50岁,随访到2019年的死亡率。EAA是根据Horvath的残差计算的,汉纳姆,血,Pheno,张,林,Weidner,Vidal-Bralo和Grim表观遗传时钟随实际年龄回归。使用cox比例风险回归,我们估计了EAA(每5年)和DunedinPoAm衰老速度(每10%增加)与总体的关联的风险比(HR)和95%置信区间(CI)。心血管和癌症死亡率,调整协变量和白细胞组成。
■在17.5年的中位随访期间,998人死亡,包括心血管疾病的272和癌症的209。GrimEAA预测总死亡率最显著(P<0.0001;HR:1.50,95%CI:1.32-1.71),其次是Hannum(P=0.001;HR:1.16,95%CI:1.07-1.27),Pheno(P=0.001;HR:1.13,95%CI:1.05-1.21),Horvath(P=0.007;HR:1.13,95%CI:1.04-1.22)和Vidal-Bralo(P=0.008;HR:1.13,95%CI:1.03-1.23)EAA。严峻的EAA预测心血管死亡率(P<0.0001;HR:1.55,95%CI:1.29-1.86),而Hannum(P=0.006;HR:1.24,95%CI:1.07-1.44),Horvath(P=0.02;HR:1.18,95%CI:1.02-1.35)和Grim(P=0.049;HR:1.37,95%CI:1.00-1.87)EAA预测癌症死亡率。DunedinPoAm的衰老速度与总体(P=0.003;HR:1.23,95%CI:1.08-1.38)和心血管(P=0.04;HR:1.25,95%CI:1.01-1.55)死亡率相关。
■在美国代表性样本中,Horvath,汉纳姆,Pheno,Vidal-Bralo和GrimEAA都预测了总死亡率,但只有GrimEAA预测了心血管死亡率和Horvath,Hannum或GrimEAA预测癌症死亡率。衰老的速度预测总体和心血管死亡率。
UNASSIGNED: Epigenetic clocks have emerged as novel measures of biological age and potential predictors of mortality. We aimed to test whether epigenetic age acceleration (EAA) estimated using different epigenetic clocks predict long-term overall, cardiovascular or cancer mortality.
UNASSIGNED: We analyzed data from 2,105 participants to the 1999-2002 National Health and Nutrition Examination Survey aged ≥50 years old who were followed for mortality through 2019. EAAs was calculated from the residuals of Horvath, Hannum, SkinBlood, Pheno, Zhang, Lin, Weidner, Vidal-Bralo and Grim epigenetic clocks regressed on chronological age. Using cox proportional hazards regression, we estimated the hazard ratio (HR) and 95% confidence interval (CI) for the association of EAA (per 5-year) and the DunedinPoAm pace of aging (per 10% increase) with overall, cardiovascular and cancer mortality, adjusting for covariates and white blood cell composition.
UNASSIGNED: During a median follow-up of 17.5 years, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (P < 0.0001; HR: 1.50, 95% CI: 1.32-1.71) followed by Hannum (P = 0.001; HR: 1.16, 95% CI: 1.07-1.27), Pheno (P = 0.001; HR: 1.13, 95% CI: 1.05-1.21), Horvath (P = 0.007; HR: 1.13, 95% CI: 1.04-1.22) and Vidal-Bralo (P = 0.008; HR: 1.13, 95% CI: 1.03-1.23) EAAs. Grim EAA predicted cardiovascular mortality (P < 0.0001; HR: 1.55, 95% CI: 1.29-1.86), whereas Hannum (P = 0.006; HR: 1.24, 95% CI: 1.07-1.44), Horvath (P = 0.02; HR: 1.18, 95% CI: 1.02-1.35) and Grim (P = 0.049; HR: 1.37, 95% CI: 1.00-1.87) EAAs predicted cancer mortality. DunedinPoAm pace of aging was associated with overall (P = 0.003; HR: 1.23, 95% CI: 1.08-1.38) and cardiovascular (P = 0.04; HR: 1.25, 95% CI: 1.01-1.55) mortality.
UNASSIGNED: In a U.S. representative sample, Horvath, Hannum, Pheno, Vidal-Bralo and Grim EAA all predicted overall mortality but only Grim EAA predicted cardiovascular mortality and Horvath, Hannum or Grim EAA predicted cancer mortality. Pace of aging predicted overall and cardiovascular mortality.