Testing Black-White disparities in biological aging in older adults in the United States: analysis of DNA-methylation and blood-chemistry methods

Graf, Gloria Huei-Jong; Crowe, Christopher L; Kothari, Meeraj; Kwon, Dayoon; Manly, Jennifer J.; Turney, Indira C.; Valeri, Linda; Belsky, Daniel W.

doi:10.1101/2021.03.02.21252685

Cited by 7 publications

(8 citation statements)

References 55 publications

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“…However, the literature evaluating them is fragmented. Although all of these algorithms purport to measure aging, they have surprisingly low agreement 18,19 ; articles often report promising findings from one (or more) DNA methylation algorithms, but often in different samples, and many algorithms show inconsistent associations with outcomes. 11,[20][21][22][23] Important validation steps are now being taken to rigorously evaluate multiple DNA methylation algorithms in the same study (e.g., in the Health and Retirement Survey).…”

Section: Discussionmentioning

confidence: 99%

Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

et al. 2022

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Background and ObjectivesDNA methylation algorithms are increasingly used to estimate biological aging; however, how these proposed measures of whole-organism biological aging relate to aging in the brain is not known. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Framingham Heart Study (FHS) Offspring Cohort to test the association between blood-based DNA methylation measures of biological aging and cognitive impairment and dementia in older adults.MethodsWe tested 3 “generations” of DNA methylation age algorithms (first generation: Horvath and Hannum clocks; second generation: PhenoAge and GrimAge; and third generation: DunedinPACE, Dunedin Pace of Aging Calculated from the Epigenome) against the following measures of cognitive impairment in ADNI: clinical diagnosis of dementia and mild cognitive impairment, scores on Alzheimer disease (AD) / Alzheimer disease and related dementias (ADRD) screening tests (Alzheimer's Disease Assessment Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment), and scores on cognitive tests (Rey Auditory Verbal Learning Test, Logical Memory test, and Trail Making Test). In an independent replication in the FHS Offspring Cohort, we further tested the longitudinal association between the DNA methylation algorithms and the risk of developing dementia.ResultsIn ADNI (N = 649 individuals), the first-generation (Horvath and Hannum DNA methylation age clocks) and the second-generation (PhenoAge and GrimAge) DNA methylation measures of aging were not consistently associated with measures of cognitive impairment in older adults. By contrast, a third-generation measure of biological aging, DunedinPACE, was associated with clinical diagnosis of Alzheimer disease (beta [95% CI] = 0.28 [0.08–0.47]), poorer scores on Alzheimer disease/ADRD screening tests (beta [Robust SE] = −0.10 [0.04] to 0.08[0.04]), and cognitive tests (beta [Robust SE] = −0.12 [0.04] to 0.10 [0.03]). The association between faster pace of aging, as measured by DunedinPACE, and risk of developing dementia was confirmed in a longitudinal analysis of the FHS Offspring Cohort (N = 2,264 individuals, hazard ratio [95% CI] = 1.27 [1.07–1.49]).DiscussionThird-generation blood-based DNA methylation measures of aging could prove valuable for measuring differences between individuals in the rate at which they age and in their risk for cognitive decline, and for evaluating interventions to slow aging.

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Section: Discussionmentioning

confidence: 99%

Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

et al. 2022

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“…Further, mortality differences across demographic groups mean that differences between Black and White participants, and between men and women, may be underestimated. Participation biases may compound this survival bias, especially for Black–White comparisons; Black participants in the VBS were younger and healthier than the full sample of Black participants in the HRS ( 46 ). Our estimates of Black–White disparities are, therefore, likely to be conservative.…”

Section: Discussionmentioning

confidence: 99%

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

Graf

Zhang

Domingue³

et al. 2022

PNAS Nexus

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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 tested associations of life-course social mobility with biological aging using data from participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study who provided blood-chemistry (n = 9,255) and/or DNA methylation (DNAm) data (n = 3,976). 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 suggested differential effects by racial identity; 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.

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“…Participation biases may compound this survival bias, especially for Black-White comparisons; Black participants in the Venous Blood Study were younger and healthier than the full sample of Black participants in the HRS (41). Our estimates of Black-White disparities are therefore likely to be conservative.…”

Section: Discussionmentioning

confidence: 97%

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

Graf

Zhang²,

Domingue³

et al. 2021

Preprint

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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.

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Testing Black-White disparities in biological aging in older adults in the United States: analysis of DNA-methylation and blood-chemistry methods

Cited by 7 publications

References 55 publications

Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

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

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

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