Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study.

Importance: People who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements of the pace of biological aging could offer intermediate end points for studies of how interventions to promote education will affect healthy longevity. Objective: To test the hypothesis that upward educational mobility is associated with a slower pace of biological aging and increased longevity. Design, Setting, and Participants: This prospective cohort study analyzed data from 3 generations of participants in the Framingham Heart Study: (1) the original cohort, enrolled beginning in 1948; (2) the Offspring cohort, enrolled beginning in 1971; and (3) the Gen3 cohort, enrolled beginning in 2002. A 3-generation database was constructed to quantify intergenerational educational mobility. Mobility data were linked with blood DNA-methylation data collected from the Offspring cohort in 2005 to 2008 (n = 1652) and the Gen3 cohort in 2009 to 2011 (n = 1449). Follow-up is ongoing. Data analysis was conducted from June 2022 to November 2023 using data obtained from the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Exposure: Educational mobility was measured by comparing participants' educational outcomes with those of their parents. Main Outcomes and Measures: The pace of biological aging was measured from whole-blood DNA-methylation data using the DunedinPACE epigenetic clock. For comparison purposes, the analysis was repeated using 4 other epigenetic clocks. Survival follow-up was conducted through 2019. Results: This study analyzed data from 3101 participants from the Framingham Heart Study; 1652 were in the Offspring cohort (mean [SD] age, 65.57 [9.22] years; 764 [46.2%] male) and 1449 were in the Gen3 cohort (mean [SD] age, 45.38 [7.83] years; 691 [47.7%] male). Participants who were upwardly mobile in educational terms tended to have slower pace of aging in later life (r = -0.18 [95% CI, -0.23 to -0.13]; P < .001). This pattern of association was similar across generations and held in within-family sibling comparisons. There were 402 Offspring cohort participants who died over the follow-up period. Upward educational mobility was associated with lower mortality risk (hazard ratio, 0.89 [95% CI, 0.81 to 0.98]; P = .01). Slower pace of aging accounted for approximately half of this association. Conclusions and Relevance: This cohort study's findings support the hypothesis that interventions to promote educational attainment may slow the pace of biological aging and promote longevity. Epigenetic clocks have potential as near-term outcome measures of intervention effects on healthy aging. Experimental evidence is needed to confirm findings.

Testing Black-White Disparities in Biological Aging Among Older Adults in the United States: Analysis of DNA-Methylation and Blood-Chemistry Methods.

Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of 8 DNA-methylation (DNAm) and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the 2016 wave of the Health and Retirement Study (n = 9,005). We quantified biological aging from 4 DNAm "clocks" (Horvath, Hannum, PhenoAge, and GrimAge clock), a DNAm pace-of-aging measure (DunedinPoAm), and 3 blood-chemistry measures (PhenoAge, Klemera-Doubal method biological age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical performance tests, self-reported limitations in activities of daily living, and physician-diagnosed chronic diseases, self-rated health, and survival. DNAm and blood-chemistry quantifications of biological aging were moderately correlated (Pearson's r = 0.1-0.4). The GrimAge clock, DunedinPoAm, and all 3 blood-chemistry measures were associated with healthspan characteristics (e.g., mortality effect-size hazard ratios were 1.71-2.32 per standard deviation of biological aging) and showed evidence of more advanced/faster biological aging in Black participants than in White participants (Cohen's d = 0.4-0.5). These measures accounted for 13%-95% of Black-White differences in healthspan-related characteristics. Findings suggest that reducing disparities in biological aging can contribute to building health equity.

Associations of Loneliness and Social Isolation With Health Span and Life Span in the U.S. Health and Retirement Study.

BACKGROUND: Loneliness and social isolation are emerging public health challenges for aging populations. METHODS: We followed N = 11 302 U.S. Health and Retirement Study participants aged 50-95 from 2006 to 2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018. RESULTS: During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at 2 or more follow-up assessments. For social isolation, these fractions were 21% and 8%. Health and Retirement Study participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen's d for persistent loneliness and social isolation = 0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk. CONCLUSIONS: Deficits in social connectedness prevalent in a national sample of U.S. older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.