DNA methylation profile is a quantitative measure of biological aging in children

Wu, Xiaohui; Chen, Weidan; Lin, Fangqin; Huang, Qingsheng; Zhong, Jiayong; Gao, Huan; Song, Yanyan; Liang, Huiying

doi:10.18632/aging.102399

Cited by 43 publications

(41 citation statements)

References 62 publications

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“…DNA methylation gestational age was estimated from cord blood DNA methylation data, using Bohlin’s epigenetic clock [ 13 ]. This clock estimates gestational age based on DNA methylation levels of 96 CpGs from HumanMethylation450 BeadChip selected trough Lasso-regression [ 21 ]. At birth, children had older clinically determined gestational age (median 40.2 weeks (95% range 37.0, 42.4)) than DNA methylation gestational age (median 39.4 weeks (95% range 37.2, 40.8)).…”

Section: Resultsmentioning

confidence: 99%

“…Contrary to adults, there is no clear pattern in the directionality of associations of beneficial or detrimental prenatal exposures and gestational age acceleration [ 19 ]. For child ages, two clocks have been developed [ 20 , 21 ]. However, in blood DNA methylation samples, these clocks were outperformed by the ‘skin and blood clock,’ which is developed among participants with a broad age range [ 15 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

et al. 2021

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Background Hypertension and atherosclerosis may partly originate in early life. Altered epigenetic aging may be a mechanism underlying associations of early-life exposures and the development of cardiovascular risk factors in childhood. A discrepancy between chronological age and age predicted from neonatal DNA methylation data is referred to as age acceleration. It may either be positive, if DNA methylation age is older than clinical age, or negative, if DNA methylation age is younger than chronological age. We examined associations of age acceleration at birth (‘gestational age acceleration’), and of age acceleration at school-age, with blood pressure and with intima-media thickness and distensibility of the common carotid artery, as markers of vascular structure and function, respectively, measured at age 10 years. Results This study was embedded in the Generation R Study, a population-based prospective cohort study. We included 1115 children with information on cord blood DNA methylation and blood pressure, carotid intima-media thickness or carotid distensibility. Gestational age acceleration was calculated using the Bohlin epigenetic clock, which was developed specifically for cord blood DNA methylation data. It predicts gestational age based on methylation levels of 96 CpGs from HumanMethylation450 BeadChip. We observed no associations of gestational age acceleration with blood pressure, carotid intima-media thickness or carotid distensibility at age 10 years. In analyses among children with peripheral blood DNA methylation measured at age 6 (n = 470) and 10 (n = 449) years, we also observed no associations of age acceleration at these ages with the same cardiovascular outcomes, using the ‘skin and blood clock,’ which predicts age based on methylation levels at 391 CpGs from HumanMethylation450 BeadChip. Conclusions Our findings do not provide support for the hypothesis that altered epigenetic aging during the earliest phase of life is involved in the development of cardiovascular risk factors in childhood.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

et al. 2021

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“…To date, many other DNA methylation clocks have been developed for different purposes and tissue targets. 3,4,6–18 Since their inception, epigenetic clocks have been used to analyze DNA methylation profiles of diverse human cohorts, uncovering previously unknown associations between accelerated ageing and a great number of health-related features. 19,20 These associations indicate that epigenetic clocks do not just track chronological age, but also biological features that are relevant to the ageing process.…”

Section: Introductionmentioning

confidence: 99%

Current perspectives on the cellular and molecular features of epigenetic ageing

Raj

Horvath

2020

Exp Biol Med (Maywood)

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It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure methylation status of specific sites on the DNA. It was observed that while the methylation of some sites does indeed decrease with age, that of others increase or remain unchanged. The application of machine learning methods to these quantitative changes in multiple sites, allowed the generation of a highly accurate estimator of age, called the epigenetic clock. The application of this clock on large human epidemiological data sets revealed that discordance between the predicted (epigenetic age) and chronological age is associated with many age-related pathologies, particularly when the former is greater than the latter. The epigenetic clock clearly captures to some degree, biological features that accompany the ageing process. Despite the ever-increasing scope of pathologies that are found to be associated with accelerated epigenetic ageing, the basic principles that underlie the ticking of the clock remain elusive. Here, we describe the known molecular and cellular attributes of the clock and consider their properties, and proffer opinions as to how they may be connected and what might be the underlying mechanism. Emerging from these considerations is the inescapable view that epigenetic ageing begins from very early moments after the embryonic stem cell stage and continues un-interrupted through the entire life-course. This appears to be a consequence of processes that are necessary for the development of the organism from conception and to maintain it thereafter through homeostasis. Hence, while the speed of ageing can, and is affected by external factors, the essence of the ageing process itself is an integral part of, and the consequence of the development of life. Impact statement The field of epigenetic ageing is relatively new, and the speed of its expansion presents a challenge in keeping abreast with new discoveries and their implications. Several reviews have already addressed the great number of pathologies, health conditions, life-style, and external stressors that are associated with changes to the rate of epigenetic ageing. While these associations highlight and affirm the ability of epigenetic clock to capture biologically meaningful changes associated with age, they do not inform us about the underlying mechanisms. In this very early period since the development of the clock, there have been rather limited experimental research that are aimed at uncovering the mechanism. Hence, the perspective that we proffer is derived from available but nevertheless limited lines of evidence that together provide a seemingly coherent narrative that can be tested. This, we believe would be helpful towards uncovering the workings of the epigenetic clock.

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“…Several DNAm clocks were developed specifically from blood or buccal epithelial cells of children and adolescents. 45,46 These clocks performed well and exhibited a high level of precision for prediction of chronological age. Several epigenetic clocks containing fewer CpGs have also been shown to exhibit a high degree of accuracy.…”

Section: Dna Methylation Clocks In Animals and Humansmentioning

confidence: 87%

“…This DNAm clock is commonly referred to as “Hannum’s clock”. 3 Since this DNAm clock was based primarily on adult blood samples, Hannum’s clock is thought to be less accurate for children 44–46 and non-blood tissue, 3 when compared to DNAm clocks optimized for those purposes. Several DNAm clocks were developed specifically from blood or buccal epithelial cells of children and adolescents.…”

Section: Dna Methylation Clocks In Animals and Humansmentioning

confidence: 99%

The use of DNA methylation clock in aging research

Liu

Shi

2020

Exp Biol Med (Maywood)

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One of the key characteristics of aging is a progressive loss of physiological integrity, which weakens bodily functions and increases the risk of death. A robust biomarker is important for the assessment of biological age, the rate of aging, and a person's health status. DNA methylation clocks, novel biomarkers of aging, are composed of a group of cytosine-phosphate-guanine dinucleotides, the DNA methylation status of which can be used to accurately measure subjective age. These clocks are considered accurate biomarkers of chronological age for humans and other vertebrates. Numerous studies have demonstrated these clocks to quantify the rate of biological aging and the effects of longevity and anti-aging interventions. In this review, we describe the purpose and use of DNA methylation clocks in aging research.

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DNA methylation profile is a quantitative measure of biological aging in children

Cited by 43 publications

References 62 publications

Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

Current perspectives on the cellular and molecular features of epigenetic ageing

The use of DNA methylation clock in aging research

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