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

对非人类物种的研究表明，女性生殖可能以维护和修复身体为代价，影响健康和寿命。利用历史记录的研究表明，在人类女性中也存在类似的“生殖成本”，但常常被无法测量的社会和环境因素所混淆，这些因素模糊了生殖与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”的测量方法来更好地理解人类这些生活史的权衡。通过检查女性生命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，从而更清楚地了解生殖成本。揭示导致妇女生育成本的分子途径可以为诊断和治疗与年龄有关的疾病提供新的策略。该项目还将支持研究生培训和长期研究合作。研究人员将分析宿雾纵向健康和营养调查的195名妇女的数据，以测试在13年的时间里，怀孕次数多的妇女是否有更快生物衰老的迹象。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——将在女性生育高峰期进行计算，并与每位女性表观遗传年龄的变化速度进行比较。表观遗传年龄是通过计算DNA的化学修饰来计算的，在多个人群中是负面健康结果和死亡率的有力预测指标。研究人员还将研究155名老年妇女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、全面的年龄相关衰退调查结合起来。这将是第一个研究生殖对女性表观遗传年龄影响的研究，并将为未来旨在阐明生殖与人类晚年结果之间联系的研究提供重要基础。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.