Lifecourse determinants and outcomes of epigenetic age acceleration across two generations

两代人的生命历程决定因素和表观遗传年龄加速的结果

• 批准号: 10618972
• 负责人: Christopher Kuzawa
• 金额: $ 52.31万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618972
• 关键词: Acceleration; Address; Adult; Affect; Age; Age Years; Aging; Atherosclerosis; Biological Aging; Biological Markers; Birth; Blood Pressure; Body Composition; Body Weight Changes; Case Study; Chemicals; Child; Childhood; Chromosomes; Chronic; Chronic Disease; Chronology; Cognition; Collaborations; Communicable Diseases; DNA; DNA Library; DNA Methylation; Data; Degenerative Disorder; Development; Disease; Disease Progression; Economics; Elderly; Environment; Environmental Risk Factor; Epigenetic Process; Evaluation; Expenditure; Future; Generations; Genetic; Goals; Growth; Health; Health Surveys; Healthcare; Heterogeneity; Human; Individual; Infection; Infrastructure; Intervention; Life; Life Cycle Stages; Life Expectancy; Life Experience; Life Extension; Life Style; Longevity; Low Birth Weight Infant; Malnutrition; Measures; Memory; Modeling; Mothers; Nutrition Surveys; Outcome; Participant; Pathway interactions; Pattern; Philippines; Population; Predictive Factor; Process; Public Health; Records; Research; Risk; Risk Factors; Role; Sampling; Surveys; Testing; Time; Variant; Weight Gain; Woman; age related; aging population; biodemography; cohort; design; early life exposure; emerging adult; experience; fasting glucose; follow-up; functional decline; healthy aging; human old age (65+); improved; indexing; infancy; innovation; lifestyle factors; low and middle-income countries; metropolitan; modifiable lifestyle factors; mortality; mortality risk; novel strategies; nutrition; offspring; preventive intervention; prospective; rate of change; reproductive; sample collection; senescence; tool; trend; young adult

PROJECT SUMMARY/ABSTRACT This study will evaluate the utility of epigenetic age as a new biological marker of aging in a large study that has followed mothers and their offspring for more than 35 years. Aging is a result not only of adult lifestyle, but also of the conditions under which we grow and develop many decades prior. This makes it challenging to study the causes of aging in humans. The recently described “epigenetic clock” records a cumulative index of past experiences while also predicting future mortality, and thus holds promise to allow new approaches to the study of healthy aging and its causes. Epigenetic age is calculated from chemical changes in chromosomes (DNA methylation) that accumulate with high predictability as individuals age. When an individual has an epigenetic age that is advanced relative to their chronological age, they are at increased mortality risk independent of conventional risk factors. This study will measure epigenetic age among participants in the Cebu Longitudinal Health and Nutrition Survey, which has followed several thousand women and their children since 1983. The study is located in Metropolitan Cebu, in the Philippines, which has experienced recent improvements in life expectancy and a corresponding increase in the societal burden of chronic degenerative disease and late life functional decline. The detailed, longitudinal data from this study will be used to address three aims: 1) understand the role of early life development, such as birth size, patterns of growth and weight gain in infancy and childhood, and early life infectious diseases, as predictors of epigenetic age measured in banked DNA samples collected in 2005, when these individuals were young adults (20-22 y); 2) obtain a second DNA sample 15 years later (in 2019-20) and use these new data to study the causes of the rate of change in each individuals' epigenetic age during adulthood; Finally, the study will measure epigenetic age in DNA samples collected in 2005 from these individuals' mothers, which will 3) clarify the domains of functional decline and late life disease, including mortality, that are predicted by epigenetic age. This study is innovative because it uses detailed, longitudinal data collected across two generations to understand the causes and consequences of epigenetic age across the full lifecycle, from birth to old age. The original birth cohort will allow modeling of the developmental factors that influence epigenetic age in early adulthood, while repeat adult epigenetic age measures obtained 15 years apart will clarify which modifiable lifestyle factors predict the pace of biological aging in adulthood. Incorporating the mothers' generation will clarify this biomarker's ability to predict specific pathways of functional decline recently measured in these women, including cognition, memory, and physical ability, along with chronic disease (atherosclerosis) and mortality. This study will thus provide a detailed evaluation of the utility of this promising new biological marker of aging, while also illuminating strategies to promote healthy aging in a population experiencing a rapid increase in the elderly population.

项目摘要/摘要 这项研究将在一项大型研究中评估表观遗传时代作为衰老的新生物学标志的效用 跟随母亲及其后代已有35年以上。衰老不仅是成人生活方式的结果，而且是 也是我们在数十年之前成长和发展的条件。这使得它挑战 研究人类衰老的原因。最近描述的“表观时钟”记录了一个累积指数 过去的经验，同时还可以预测未来的死亡率，因此有望允许新的方法 研究健康衰老及其原因。表观遗传时代是根据染色体的化学变化计算的 （DNA甲基化）随着个体年龄的增长而具有高可预测性的积累。当一个人有一个 相对于年代年龄的高级表观遗传时代，死亡率的风险增加 独立于常规风险因素。这项研究将衡量参与者的表观遗传年龄 宿务纵向健康和营养调查，该调查跟踪了数千名妇女及其子女 自1983年以来。这项研究位于菲律宾的大都会宿雾，该研究经历了最近的经历 预期寿命的改善和慢性退化的社会燃烧的相应增加 疾病和生命后期功能下降。本研究的详细纵向数据将用于解决 三个目的：1）了解早期生命发展的作用，例如出生规模，增长和体重模式 婴儿期和童年以及早期生命传染病，作为表观遗传年龄的预测指标 这些人是年轻人（20-22岁），于2005年收集的库存DNA样品； 2）获取 15年后的第二个DNA样本（2019 - 20年），并使用这些新数据来研究率的原因 在成年期间每个人的表观遗传年龄的变化；最后，该研究将测量 2005年从这些人的母亲那里收集的DNA样本，这将3）阐明功能的领域 通过表观遗传时代预测的衰落和生命后期疾病，包括死亡率。这项研究是创新的 因为它使用了两代人收集的详细的，纵向数据来了解原因和 从出生到老年，整个生命周期的表观遗传时代的后果。最初的出生队列将 允许建模成年初期影响表观遗传年龄的发展因素，而重复成人 相距15年获得的表观遗传年龄措施将阐明哪些可修改的生活方式因素预测了步伐 成年生物衰老的衰老。结合母亲的一代将阐明这种生物标志物的能力 预测最近在这些女性中测量的功能下降的特定途径，包括认知， 记忆和身体能力，以及慢性疾病（动脉粥样硬化）和死亡率。因此，这项研究将 对这种承诺新的衰老生物学标志的效用提供详细的评估，同时也 阐明策略以促进健康衰老的人口中的健康衰老 人口。