Educational Mobility, the Pace of Biological Aging, and Lifespan in the Framingham Heart Study
Educational Mobility, the Pace of Biological Aging, and Lifespan in the Framingham Heart Study
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DOI：
10.1101/2023.11.04.23298091
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发表时间：
2023-11
期刊：
影响因子：
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通讯作者：
G. Graf;A. E. Aiello;A. Caspi;M. Kothari;H. Liu;T. Moffitt;P. Muennig;C. Ryan;K. Sugden-K.-S
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文献类型：
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作者：
G. Graf;A. E. Aiello;A. Caspi;M. Kothari;H. Liu;T. Moffitt;P. Muennig;C. Ryan;K. Sugden-K.-S
重要性：接受更多教育的人寿命更长，身体更健康。新的证据表明，这些好处是通过减缓生物衰老的速度来实现的。如果是这样的话，对生物衰老速度的测量可以为促进教育的干预措施如何影响健康寿命的研究提供中间终点。目的：验证学历向上流动有助于减缓生物衰老速度和延长寿命的假设。设计：前瞻性队列研究。背景：我们分析了弗雷明汉心脏研究中三代参与者的数据：1948年开始入组的原始队列，1971年开始入组的后代队列，2002年开始入组的第三代队列。后续行动正在进行中。在2022-2023年期间，使用从dbGaP （phs000007.v33）获得的数据进行数据分析。参与者：我们构建了一个三代人的数据库来量化代际教育流动。我们将流动性数据与从2005-2008年的后代队列（n= 1652）和2009-2011年的Gen3队列（n= 1449）收集的血液DNA甲基化数据联系起来。这3101个参与者组成了我们的分析样本。暴露：我们通过比较参与者与其父母的教育成果来衡量教育流动性。结果：我们使用DunedinPACE表观遗传时钟从全血dna甲基化数据中测量生物衰老的速度。为了比较，我们使用另外四个表观遗传时钟重复分析。生存随访持续到2019年。结果：在教育方面向上流动的参与者在以后的生活中往往有较慢的DunedinPACE （r=-0.18, 95% CI [-0.23,-0.13], p<0.001）。这种关联模式在几代人之间是相似的，在家庭内部的兄弟姐妹比较中也是如此。402名后代队列参与者在随访期间死亡。向上教育流动与较低的死亡风险相关（HR=0.89, 95% CI [0.81,0.98] p=0.014）。慢速达尼丁占了大约一半的关联。结论和相关性：我们的研究结果支持这样的假设，即提高受教育程度的干预措施将减缓生物衰老的步伐，并延长寿命。表观遗传时钟，如DunedinPACE，有潜力作为干预对健康衰老影响的近期结果测量。需要实验证据来证实研究结果。
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.