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The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age.

ABSTRACT: The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI34. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.

SUBMITTER: Kim S

PROVIDER: S-EPMC5352589 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age.

Kim Sangkyu S Myers Leann L Wyckoff Jennifer J Cherry Katie E KE Jazwinski S Michal SM

GeroScience 20170114 1

The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI<sub>34</sub>) composed of 34 health items, for measuring biological ag ...[more]

PMID: 28299637

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Project description:Study questionAre reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?Summary answerOur data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age.What is known alreadyA study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies.Study design, size, durationWe used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort.Participants/materials, setting, methodsData on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression.Main results and the role of chanceAll three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7).Limitations, reasons for cautionWe relied on retrospective recall to ascertain reproductive history and pregnancy complications.Wider implications of the findingsOur findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome.Study funding/competing interest(s)This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest.Trial registration numberNot applicable.

Dataset Information

The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age.

Publications

The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age.

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