DunedinPACE, a DNA methylation biomarker of the pace of aging

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods: We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

Download Full-text

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

10.1101/2021.08.30.21262858 ◽

2021 ◽

Author(s):

Daniel W Belsky ◽

Avshalom Caspi ◽

David L Corcoran ◽

Karen Sugden ◽

Richie Poulton ◽

...

Keyword(s):

Dna Methylation ◽

Blood Test ◽

Functional Decline ◽

Childhood Adversity ◽

Original Method ◽

Effect Sizes ◽

Biological Aging ◽

Retest Reliability ◽

System Integrity ◽

Test Retest Reliability

Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Here, we report an advance on our original method (Belsky et al. 2020). We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 organ-system integrity indicators across four timepoints spanning two decades to model Pace of Aging. We distilled two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and DNA-methylation data restricted to exclude probes with low test-retest reliability. The resulting measure, DunedinPACE, showed high test-retest reliability, was associated with functional decline, morbidity, and mortality, and indicated accelerated Pace of Aging in young adults with childhood adversity across five datasets. DunedinPACE effect-sizes were similar to GrimAge-clock effect-sizes and larger than those for other benchmark DNA-methylation-clocks. DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience

Download Full-text

Social mobility and biological aging among older adults in the United States

10.1101/2021.10.19.465042 ◽

2021 ◽

Author(s):

Gloria Huei-Jong Graf ◽

Yalu Zhang ◽

Benjamin W Domingue ◽

Kathleen Mullan Harris ◽

Meeraj Kothari ◽

...

Keyword(s):

Dna Methylation ◽

Social Mobility ◽

Healthy Aging ◽

Upward Mobility ◽

Blood Chemistry ◽

The United States ◽

Effect Sizes ◽

Biological Aging ◽

Educational Mobility ◽

System Integrity

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We analyzed blood-chemistry and DNA methylation (DNAm) data from n=9286 participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study to test associations of life-course social mobility with biological aging. We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation "clocks" and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ~0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility revealed differential effects by racial identity, suggesting that mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging.

Download Full-text

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

eLife ◽

10.7554/elife.54870 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 9

Author(s):

Daniel W Belsky ◽

Avshalom Caspi ◽

Louise Arseneault ◽

Andrea Baccarelli ◽

David L Corcoran ◽

...

Keyword(s):

Dna Methylation ◽

Biological Aging ◽

Surrogate Endpoints ◽

Progressive Decline ◽

Rates Of Change ◽

System Integrity ◽

Point Measure ◽

Single Time Point ◽

Time Point

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

Download Full-text

Effect sizes and test-retest reliability of the fMRI-based Neurologic Pain Signature

10.1101/2021.05.29.445964 ◽

2021 ◽

Author(s):

Xiaochun Han ◽

Yoni K. Ashar ◽

Philip Kragel ◽

Bogdan Petre ◽

Victoria Schelkun ◽

...

Keyword(s):

Individual Differences ◽

Effect Size ◽

Mental States ◽

Effect Sizes ◽

Medium Effect ◽

Retest Reliability ◽

Medium Effect Size ◽

Pain Reports ◽

Nociceptive Input ◽

Test Retest Reliability

Identifying biomarkers that predict mental states with large effect sizes and high test-retest reliability is a growing priority for fMRI research. We examined a well-established multivariate brain measure that tracks pain induced by nociceptive input, the Neurologic Pain Signature (NPS). In N = 295 participants across eight studies, NPS responses showed a very large effect size in predicting within-person single-trial pain reports (d = 1.45) and medium effect size in predicting individual differences in pain reports (d = 0.49, average r = 0.20). The NPS showed excellent short-term (within-day) test-retest reliability (ICC = 0.84, with average 69.5 trials/person). Reliability scaled with the number of trials within-person, with ≥60 trials required for excellent test-retest reliability. Reliability was comparable in two additional studies across 5-day (N = 29, ICC = 0.74, 30 trials/person) and 1-month (N = 40, ICC = 0.46, 5 trials/person) test-retest intervals. The combination of strong within-person correlations and only modest between-person correlations between the NPS and pain reports indicates that the two measures have different sources of between-person variance. The NPS is not a surrogate for individual differences in pain reports, but can serve as a reliable measure of pain-related physiology and mechanistic target for interventions.

Download Full-text

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

10.1101/2020.02.05.927434 ◽

2020 ◽

Cited By ~ 2

Author(s):

DW Belsky ◽

A Caspi ◽

L Arseneault ◽

A Baccarelli ◽

D Corcoran ◽

...

Keyword(s):

Dna Methylation ◽

Functional Decline ◽

Longitudinal Change ◽

Biological Aging ◽

Early Life Adversity ◽

Progressive Decline ◽

System Integrity ◽

Aging Study ◽

Point Measure

ABSTRACTBiological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed to serve as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood DNA-methylation measure that is sensitive to variation in the pace of biological aging among individuals born the same year. We first modeled longitudinal change in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in the Dunedin birth cohort. Rates of change in each biomarker were composited to form a measure of aging-related decline, termed Pace of Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace of Aging, called DunedinPoAm for Dunedin (P)ace (o)f (A)ging (m)ethylation. Validation analyses showed DunedinPoAm was associated with functional decline in the Dunedin Study and more advanced biological age in the Understanding Society Study, predicted chronic disease and mortality in the Normative Aging Study, was accelerated by early-life adversity in the E-risk Study, and DunedinPoAm prediction was disrupted by caloric restriction in the CALERIE trial. DunedinPoAm generally outperformed epigenetic clocks. Findings provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

Download Full-text

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

10.7554/elife.54870.sa2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Daniel W Belsky ◽

Avshalom Caspi ◽

Louise Arseneault ◽

Andrea Baccarelli ◽

David L Corcoran ◽

...

Keyword(s):

Dna Methylation ◽

Blood Test ◽

Author Response ◽

Biological Aging

Download Full-text

Recommended motor assessments based on psychometric properties in individuals with dementia: a systematic review

European Review of Aging and Physical Activity ◽

10.1186/s11556-019-0228-z ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 2

Author(s):

Sandra Trautwein ◽

Philipp Maurus ◽

Bettina Barisch-Fritz ◽

Anela Hadzic ◽

Alexander Woll

Keyword(s):

Physical Activity ◽

Systematic Review ◽

Psychometric Properties ◽

Randomised Controlled Trials ◽

Effect Sizes ◽

Controlled Trials ◽

Retest Reliability ◽

Frequency Of Use ◽

Randomised Controlled ◽

Test Retest Reliability

Abstract Background Motor assessments are important to determine effectiveness of physical activity in individuals with dementia (IWD). However, inappropriate and non-standardised assessments without sound psychometric properties have been used. This systematic review aims to examine psychometric properties of motor assessments in IWD combined with frequency of use and effect sizes and to provide recommendations based on observed findings. We performed a two-stage systematic literature search using Pubmed, Web of Science, Cochrane Library, ALOIS, and Scopus (inception - July/September 2018, English and German). The first search purposed to identify motor assessments used in randomised controlled trials assessing effectiveness of physical activity in IWD and to display their frequency of use and effect sizes. The second search focused on psychometric properties considering influence of severity and aetiology of dementia and cueing on test-retest reliability. Two reviewers independently extracted and analysed findings of eligible studies in a narrative synthesis. Results Literature searches identified 46 randomised controlled trials and 21 psychometric property studies. While insufficient information was available for validity, we observed sufficient inter-rater and relative test-retest reliability but unacceptable absolute test-retest reliability for most assessments. Combining these findings with frequency of use and effect sizes, we recommend Functional Reach Test, Groningen Meander Walking Test (time), Berg Balance Scale, Performance Oriented Mobility Assessment, Timed Up & Go Test, instrumented gait analysis (spatiotemporal parameters), Sit-to-Stand assessments (repetitions> 1), and 6-min walk test. It is important to consider that severity and aetiology of dementia and cueing influenced test-retest reliability of some assessments. Conclusion This review establishes an important foundation for future investigations. Sufficient relative reliability supports the conclusiveness of recommended assessments at group level, while unacceptable absolute reliability advices caution in assessing intra-individual changes. Moreover, influences on test-retest reliability suggest tailoring assessments and instructions to IWD and applying cueing only where it is inevitable. Considering heterogeneity of included studies and insufficient examination in various areas, these recommendations are not comprehensive. Further research, especially on validity and influences on test-retest reliability, as well as standardisation and development of tailored assessments for IWD is crucial. This systematic review was registered in PROSPERO (CRD42018105399).

Download Full-text

Reliability, and Convergent and Discriminant Validity of Gaming Disorder Scales: A Meta-Analysis

Frontiers in Psychology ◽

10.3389/fpsyg.2021.764209 ◽

2021 ◽

Vol 12 ◽

Author(s):

Seowon Yoon ◽

Yeji Yang ◽

Eunbin Ro ◽

Woo-Young Ahn ◽

Jueun Kim ◽

...

Keyword(s):

Systematic Review ◽

Internet Addiction ◽

Discriminant Validity ◽

Meta Analysis ◽

Effect Sizes ◽

Gaming Disorder ◽

Reliability Generalization ◽

Retest Reliability ◽

Convergent And Discriminant Validity ◽

Test Retest Reliability

Background: An association between gaming disorder (GD) and the symptoms of common mental disorders is unraveled yet. In this preregistered study, we quantitatively synthesized reliability, convergent and discriminant validity of GD scales to examine association between GD and other constructs.Methods: Five representative GD instruments (GAS-7, AICA, IGDT-10, Lemmens IGD-9, and IGDS9-SF) were chosen based on recommendations by the previous systematic review study to conduct correlation meta-analyses and reliability generalization. A systematic literature search was conducted through Pubmed, Proquest, Embase, and Google Scholar to identify studies that reported information on either reliability or correlation with related variables. 2,124 studies were full-text assessed as of October 2020, and 184 were quantitatively synthesized. Conventional Hedges two-level meta-analytic method was utilized.Results: The result of reliability generalization reported a mean coefficient alpha of 0.86 (95% CI = 0.85–0.87) and a mean test-retest estimate of 0.86 (95% CI = 0.81–0.89). Estimated effect sizes of correlation between GD and the variables were as follows: 0.33 with depression (k = 45; number of effect sizes), 0.29 with anxiety (k = 37), 0.30 with aggression (k = 19), –0.22 with quality of life (k = 18), 0.29 with loneliness (k = 18), 0.56 with internet addiction (k = 20), and 0.40 with game playtime (k = 53), respectively. The result of moderator analyses, funnel and forest plots, and publication bias analyses were also presented.Discussion and Conclusion: All five GD instruments have good internal consistency and test-retest reliability. Relatively few studies reported the test-retest reliability. The result of correlation meta-analysis revealed that GD scores were only moderately associated with game playtime. Common psychological problems such as depression and anxiety were found to have a slightly smaller association with GD than the gaming behavior. GD scores were strongly correlated with internet addiction. Further studies should adopt a rigorous methodological procedure to unravel the bidirectional relationship between GD and other psychopathologies.Limitations: The current study did not include gray literature. The representativeness of the five tools included in the current study could be questioned. High heterogeneity is another limitation of the study.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42020219781].

Download Full-text