Dataset Information

Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions.

ABSTRACT: The DNA methylation levels of certain CpG sites are thought to reflect the pace of human aging. Here, we developed a robust predictor of mouse biological age based on 90 CpG sites derived from partial blood DNA methylation profiles. The resulting clock correctly determines the age of mouse cohorts, detects the longevity effects of calorie restriction and gene knockouts, and reports rejuvenation of fibroblast-derived iPSCs. The data show that mammalian DNA methylomes are characterized by CpG sites that may represent the organism's biological age. They are scattered across the genome, they are distinct in human and mouse, and their methylation gradually changes with age. The clock derived from these sites represents a biomarker of aging and can be used to determine the biological age of organisms and evaluate interventions that alter the rate of aging.

SUBMITTER: Petkovich DA

PROVIDER: S-EPMC5578459 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions.

Petkovich Daniel A DA Podolskiy Dmitriy I DI Lobanov Alexei V AV Lee Sang-Goo SG Miller Richard A RA Gladyshev Vadim N VN

Cell metabolism 20170401 4

The DNA methylation levels of certain CpG sites are thought to reflect the pace of human aging. Here, we developed a robust predictor of mouse biological age based on 90 CpG sites derived from partial blood DNA methylation profiles. The resulting clock correctly determines the age of mouse cohorts, detects the longevity effects of calorie restriction and gene knockouts, and reports rejuvenation of fibroblast-derived iPSCs. The data show that mammalian DNA methylomes are characterized by CpG site ...[more]

PMID: 28380383

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Project description:STUDY QUESTION:Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age? SUMMARY ANSWER:Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age. WHAT IS KNOWN ALREADY:A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies. STUDY DESIGN, SIZE, DURATION:We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS:Data 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 ?-values and 95% CIs using linear regression. MAIN RESULTS AND THE ROLE OF CHANCE:All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: ? = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: ? = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: ? = 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 (? = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (? = 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 CAUTION:We relied on retrospective recall to ascertain reproductive history and pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS:Our 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 NUMBER:Not applicable.

Dataset Information

Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions.

Publications

Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions.

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