Quantification of the pace of biological aging in humans through a blood test: The DunedinPoAm DNA methylation algorithm

Belsky, Daniel W.; Caspi, Avshalom; Arseneault, Louise; Baccarelli, Andrea; Corcoran, David L.; Gao, Xu; Hannon, Eilís; Harrington, HL; Rasmussen, Line Jee Hartmann; Houts, Renate; Huffman, Kim M.; Kraus, WE; Kwon, Dayoon; Mill, Jonathan; Pieper, C. F.; Prinz, Joseph A.; Poulton, Richie; Schwartz, Joel; Sugden, Karen; Vokonas, Pantel; Williams, BS; Moffitt, T.E.

doi:10.1101/2020.02.05.927434

Cited by 62 publications

(150 citation statements)

References 87 publications

(61 reference statements)

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“…Faster methylation pace of aging in children with higher body mass index and more advanced pubertal development for their age, but these covariates did not account for observed socioeconomic differences. Our results suggest that DunedinPoAm is useful as a salivary biomarker that not only reflects biological aging in adulthood, as was previously established (24), but is also sensitive in realtime to social determinants of health experienced during childhood.…”

Section: Discussionsupporting

confidence: 78%

“…We used DNA-methylation algorithms to make statistical adjustment for the cellular composition of the saliva samples. Increasing confidence in our findings, they replicate results for DunedinPoAm and epigenetic clocks from blood DNA methylation measured in 18-year-olds (24). Second, because this cohort is still young, we do not know if faster aging observed in childhood will translate into higher disease risk later in life.…”

Section: Discussionsupporting

confidence: 58%

“…An alternative to epigenetic clocks is a new DNA methylation-based measurement of the pace of biological aging, DunedinPoAm (24). Whereas the clocks were developed from analysis comparing chronologically older individuals to younger ones, DunedinPoAm was developed from analysis of change over time occurring in a cohort of individuals who were all the same chronological age.…”

mentioning

confidence: 99%

“…Epigenetic clocks may, therefore, be less sensitive to changes in biological aging as compared to pace of aging measures such as DunedinPoAm. One previous study showed that DunedinPoAm indicates faster methylation pace of aging in 18 year-olds exposed to early adversity, including low childhood socioeconomic status (24). However, this new measure has not yet been studied in children.…”

mentioning

confidence: 99%

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Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescents

Raffington

Belsky

Malanchini

et al. 2020

Preprint

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Children who grow up in socioeconomically disadvantaged families face increased burden of disease and disability as they mature into adulthood. One hypothesized mechanism for this increased burden is that early-life disadvantage and its associated psychological stress accelerate biological processes of aging, increasing vulnerability to subsequent disease. In order to evaluate this hypothesis and the potential impact of preventive interventions, measures to quantify the early acceleration of biological aging in childhood are needed. Here, we evaluated a novel DNAmethylation measure of the pace of aging, DunedinPoAm, and compared DunedinPoAm results with results for several published epigenetic clocks. Data on saliva DNA-methylation and socioeconomic circumstances were collected from N = 600 children and adolescents aged 8-to 18-years-old (48% female) participating in the Texas Twin Project. Participants living in more disadvantaged families and neighborhoods exhibited faster pace of aging (r = 0.18, p = 0.001 for both). Latinx-identifying children exhibited faster DunedinPoAm compared to both White-and Latinx-White-identifying children, consistent with higher levels of disadvantage in this group.Children with more advanced pubertal development and those with had higher body-mass index also exhibited faster DunedinPoAm, but these covariates did not account for the observed socioeconomic gradient in methylation pace of aging. In contrast to findings for DunedinPoAm, we did not detect associations of socioeconomic disadvantage with five published epigenetic clocks. Findings suggest that DNA-methylation pace-of-aging measures may prove more sensitive to health damaging effects of adversity, particularly when measurements are taken early in the life course, before substantial aging has occurred.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescents

Raffington

Belsky

Malanchini

et al. 2020

Preprint

Self Cite

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“…However, we recently reported that a proxy for the Pace of Aging can now be quantified from genome-wide DNA methylation data extracted from a single cross-sectional blood draw. 47 This measure makes it possible for studies lacking 4 waves of biomarkers to extend this work; e.g., it predicts disease and mortality in U.S. and U.K. samples. 47 Fourth, while associations were consistent across domains and measures, effect-sizes were generally moderate.…”

Section: Discussionmentioning

confidence: 99%

Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

Elliott

Caspi

Houts

et al. 2021

Preprint

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All humans age, but some age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between biological aging and indicators of future frailty risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants' Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, hepatic, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years, in 2019. Participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.

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“Epigenetic clocks”: Theory and applications in human biology

Ryan

2020

American J Hum Biol

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All humans age, but how we age—and how fast—differs considerably from person to person. This deviation between apparent age and chronological age is often referred to as “biological age” (BA) and until recently robust tools for studying BA have been scarce. “Epigenetic clocks” are starting to change this. Epigenetic clocks use predictable changes in the epigenome, usually DNA methylation, to estimate chronological age with unprecedented accuracy. More importantly, deviations between epigenetic age and chronological age predict a broad range of health outcomes and mortality risks better than chronological age alone. Thus, epigenetic clocks appear to capture fundamental molecular processes tied to BA and can serve as powerful tools for studying health, development, and aging across the lifespan. In this article, I review epigenetic clocks, especially as they relate to key theoretical and applied issues in human biology. I first provide an overview of how epigenetic clocks are constructed and what we know about them. I then discuss emerging applications of particular relevance to human biologists—those related to reproduction, life‐history, stress, and the environment. I conclude with an overview of the methods necessary for implementing epigenetic clocks, including considerations of study design, sample collection, and technical considerations for processing and interpreting epigenetic clocks. The goal of this review is to highlight some of the ways that epigenetic clocks can inform questions in human biology, and vice versa, and to provide human biologists with the foundational knowledge necessary to successfully incorporate epigenetic clocks into their research.

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Quantification of the pace of biological aging in humans through a blood test: The DunedinPoAm DNA methylation algorithm

Cited by 62 publications

References 87 publications

Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescents

Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescents

Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

“Epigenetic clocks”: Theory and applications in human biology

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