Educational Mobility, the Pace of Biological Aging, and Lifespan 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 biological aging could offer intermediate endpoints for studies of how interventions to promote education will impact healthy longevity. Objective: To test the hypothesis that upward educational mobility contributes to a slower pace of biological aging and increased longevity. Design: Prospective cohort study. Setting: We analyzed data from three generations of participants in the Framingham Heart Study: the Original cohort, enrolled beginning in 1948, the Offspring cohort, enrolled beginning in 1971, and the Gen3 cohort, enrolled beginning in 2002. Follow-up is on-going. Data analysis was conducted during 2022-2023 using data obtained from dbGaP (phs000007.v33). Participants: We constructed a three-generation database to quantify intergenerational educational mobility. We linked mobility data with blood DNA methylation data collected from the Offspring cohort in (2005-2008) (n=1,652) and the Gen3 cohort in 2009-2011 (n=1,449). These n=3,101 participants formed our analysis sample. Exposure: We measured educational mobility by comparing participants' educational outcomes with those of their parents. Outcomes: We measured the pace of biological aging from whole-blood DNA-methylation data using the DunedinPACE epigenetic clock. For comparison purposes, we repeated analysis using four other epigenetic clocks. Survival follow-up was conducted through 2019. Results: Participants who were upwardly mobile in educational terms tended to have slower DunedinPACE in later life (r=-0.18, 95% CI [-0.23,-0.13], p<0.001). This pattern of association was similar across generations and held in within-family sibling comparisons. 402 Offspring-cohort participants died over the follow-up period. Upward educational mobility was associated with lower mortality risk (HR=0.89, 95% CI [0.81,0.98] p=0.014). Slower DunedinPACE accounted for roughly half of this association. Conclusions and Relevance: Our findings support the hypothesis that interventions to promote educational attainment will slow the pace of biological aging and promote longevity. Epigenetic clocks, like DunedinPACE, have potential as near-term outcome measures of intervention effects on healthy aging. Experimental evidence is needed to confirm findings. ### Competing Interest Statement AC, TEM, KS, and DWB are listed as inventors on the Duke University and University of Otago Invention DunedinPACE, which is licensed to TruDiagnostic. ### Funding Statement This project was supported by US National Institutes of Health Grants R01AG073402, R01AG073207, and R21AG078627. GG is supported by T32ES023772. DWB is a fellow of the CIFAR CBD Network. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data from the Framingham Offspring Study obtained from dbGaP (phs000007.v33.p14 and phs000724.v10.p14). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors