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      Epigenetic and accelerated age in captive olive baboons ( Papio anubis), and relationships with walking speed and fine motor performance

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          Abstract

          Epigenetic age, estimated by DNA methylation across the genome, reflects biological age. Accelerated age (i.e., an older methylation age than expected given chronological age) is an accepted aging biomarker in humans, showing robust associations with deleterious health outcomes, longevity, and mortality. However, data regarding age acceleration in nonhuman primates (NHPs), and relationships between NHP epigenetic age and behavioral indicators of aging, such as walking speed and fine motor performance, are sparse. We measured DNA methylation of 140 captive olive baboons ( Papio anubis) (84% female, 3-20 years-old), estimated their epigenetic ages, and classified them as showing age acceleration or deceleration. We found that epigenetic age was strongly correlated with chronological age, and that approximately 27% of the sample showed age acceleration and 28% showed age deceleration. We subsequently examined relationships between epigenetic and accelerated age and walking speed (N=129) and fine motor performance (N=39). Older animals showed slower speeds and poorer motor performance. However, the difference between the epigenetic age and chronological age, referred to as delta age, was not a consistent predictor of walking speed or fine motor performance. These data highlight the need for further examination of age acceleration across NHP species, and the ways that age acceleration may (not) be related to indicators of aging in NHP models.

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          Genome-wide methylation profiles reveal quantitative views of human aging rates.

          The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Here, we build a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual's methylome ages, which we show is impacted by gender and genetic variants. We also show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. Moreover, we show how our aging model is upheld in other human tissues and reveals an advanced aging rate in tumor tissue. Our model highlights specific components of the aging process and provides a quantitative readout for studying the role of methylation in age-related disease. Copyright © 2013 Elsevier Inc. All rights reserved.
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            DNA methylation-based biomarkers and the epigenetic clock theory of ageing

            Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?
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              DNA methylation age of blood predicts all-cause mortality in later life

              Background DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43. Conclusions DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0584-6) contains supplementary material, which is available to authorized users.

                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 March 2025
                18 March 2025
                : 17
                : 3
                : 740-756
                Affiliations
                [1 ]The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, National Center for Chimpanzee Care, TX 78602, USA
                [2 ]Texas State University, Department of Biology Supple Science Building, TX 78666, USA
                [3 ]Department of Ecology and Evolution and Marine Biology, Department of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA
                Author notes
                Correspondence to: Sarah Neal; email: SJNeal@MDAnderson.org
                Article
                206223 206223
                10.18632/aging.206223
                11984432
                40105865
                b1af4ce5-c1d4-41db-86e7-c89e376cd151
                Copyright: © 2025 Neal et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 April 2024
                : 06 March 2025
                Categories
                Research Paper

                Cell biology
                epigenetics,dna methylation,baboons,behavioral indicators,accelerating aging
                Cell biology
                epigenetics, dna methylation, baboons, behavioral indicators, accelerating aging

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