Dataset Information

Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

ABSTRACT: The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphate-guanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.

SUBMITTER: Belsky DW

PROVIDER: S-EPMC6248475 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Belsky Daniel W DW Moffitt Terrie E TE Cohen Alan A AA Corcoran David L DL Levine Morgan E ME Prinz Joseph A JA Schaefer Jonathan J Sugden Karen K Williams Benjamin B Poulton Richie R Caspi Avshalom A

American journal of epidemiology 20180601 6

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using re ...[more]

PMID: 29149257

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Project description:ImportanceNeighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood.ObjectiveTo evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation.Design, setting, and participantsThis cross-sectional study used data from the Sister Study, a prospective cohort study comprising 50 884 women living in the US and Puerto Rico aged 35 to 74 years at enrollment who had a sister with breast cancer but had not had breast cancer themselves. Cohort enrollment occurred between July 2003 and March 2009. Participants completed a computer-assisted telephone interview on demographic, socioeconomic, lifestyle, and residential factors and provided anthropometric measures and peripheral blood samples at a home examination. DNA methylation data obtained for 2630 non-Hispanic White women selected for a case-cohort study in 2014 were used in this cross-sectional analysis. DNA methylation was measured using the HumanMethylation450 BeadChips in whole blood samples collected at baseline. Data analysis for this study was performed from October 17, 2019, to August 27, 2020.ExposuresEach participants' primary address was linked to an established index of neighborhood deprivation.Main outcomes and measuresEpigenetic age was estimated using 4 epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge). Age acceleration was determined using residuals from regressing chronologic age on each of the 4 epigenetic age metrics. Linear regression was used to estimate associations between neighborhood deprivation and epigenetic age acceleration as well as DNA methylation at individual cytosine-guanine sites across the genome.ResultsMean (SD) age of the 2630 participants was 56.9 (8.7) years. Those with the greatest (>75th percentile) vs least (≤25th percentile) neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum (β = 0.23; 95% CI, 0.01-0.45), PhenoAge (β = 0.28; 95% CI, 0.06-.50), and GrimAge (β = 0.37; 95% CI, 0.12-0.62). Increasing US quartiles of neighborhood deprivation exhibited a trend with Hannum, PhenoAge, and GrimAge. For example, GrimAge showed a significant dose-response (P test for trend <.001) as follows: level 2 vs level 1 (β = 0.30; 95% CI, 0.17-0.42), level 3 vs level 1 (β = 0.35; 95% CI, 0.19-0.50), and level 4 vs level 1 (β = 0.37; 95% CI, 0.12-0.62). Neighborhood deprivation was found to be associated with 3 cytosine-phosphate-guanine sites, with 1 of these annotated to a known gene MAOB (P = 9.71 × 10-08).Conclusions and relevanceThe findings of this study suggest that residing in a neighborhood with a higher deprivation index appears to be reflected by methylation-based markers of aging.

Dataset Information

Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Publications

Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

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