Doctoral Dissertation Research: Quantifying the Costs of Human Reproduction using the 'Epigenetic Clock'

对非人类物种的研究表明，女性生殖可能是以维护和修复身体为代价的，这会影响健康和寿命。使用历史记录的研究表明，人类女性的生育成本类似，但经常被无法测量的社会和环境因素混淆，这些因素掩盖了生殖和寿命之间的因果关系。这个博士论文项目将使用一种新的“表观遗传年龄”测量方法来更好地理解人类的这些生活史权衡。通过研究女性一生中几个时间点的生殖年龄和表观遗传年龄，可以解释社会和环境对衰老的影响，从而对生育成本有更清晰的了解。揭示导致女性生育成本的分子途径，可以为诊断和治疗与年龄相关的疾病提供新的战略。该项目还将支持研究生培训和长期研究合作。调查人员将分析195名参与宿务纵向健康和营养调查的女性的数据，以测试在13年的时间里，怀孕次数更多的女性是否表现出更快的生物衰老迹象。孩子的数量、性别、大小和生育间隔--以及分配给母乳喂养的能量--将在女性的生育高峰期计算出来，并与每个女性表观遗传年龄的速度变化进行比较。表观遗传年龄是通过计算对DNA进行的化学修饰来计算的，它是多个人群中负面健康结果和死亡率的强烈预测因子。研究人员还将研究155名老年女性的生殖和表观遗传年龄之间的关系，他们将把这些数据与一项单独的、全面的年龄相关下降调查结合起来。这将是第一次研究生殖对女性表观遗传年龄的影响，并将为未来旨在澄清生殖与人类晚年结果之间联系的研究提供重要的基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Research on non-human species suggests that female reproduction may come at a cost to maintaining and repairing the body, affecting both health and lifespan. Studies using historical records suggest a similar 'cost of reproduction' in human females, but are often confounded by unmeasured social and environmental factors that obscure causal relationships between reproduction and lifespan. This doctoral dissertation project will use a new measure of 'epigenetic age' to better understand these life history trade-offs in humans. By examining both reproduction and epigenetic age at several time points in a woman's life, social and environmental effects on aging can be accounted for, yielding a clearer picture of the costs of reproduction. Uncovering the molecular pathways responsible for costs of reproduction in women could inform new strategies for diagnosing and treating age-related diseases. This project will also support graduate student training and long-term research collaborations.The investigators will analyze data for 195 women who are part of the Cebu Longitudinal Health and Nutrition Survey to test whether those who have had more pregnancies show signs of more rapid biological aging during a 13-year period. The number of children, their sex, size, and birth spacing - as well as energy allocated to breastfeeding - will be calculated over the women's peak reproductive lives, and compared to the pace change in each woman's epigenetic age. Epigenetic age is calculated by counting chemical modifications made to DNA, and is a strong predictor of negative health outcomes and mortality across multiple populations. The researchers will also examine the relationship between reproduction and epigenetic age among 155 older women, for whom they will combine these data with a separate, comprehensive survey of age-related decline. This will be the first study to examine the effect of reproduction on epigenetic age in females, and will provide an important foundation for future studies aimed at clarifying the links between reproduction and late life outcomes in humans.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.