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: 10201512
• 负责人: Christopher Kuzawa
• 金额: $ 49.11万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201512
• 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; Childhood Acute Lymphocytic Leukemia; 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; cohort; design; early life exposure; emerging adult; experience; fasting glucose; follow-up; functional decline; healthy aging; human old age (65+); indexing; infancy; innovation; lifestyle factors; low and middle-income countries; metropolitan; modifiable lifestyle factors; mortality; mortality risk; novel strategies; nutrition; offspring; outcome prediction; 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.

项目概要/摘要 本研究将在一项大型研究中评估表观遗传年龄作为衰老的新生物标志物的效用， 超过 35 年以来，我们一直在关注母亲及其后代的情况。 衰老不仅是成人生活方式的结果，也是成人生活方式的结果。 以及我们成长和许多人几十年前发展的条件，这使得我们面临挑战。 研究人类衰老的原因，最近描述的“表观遗传时钟”记录了一个累积指数。 过去的经验，同时也预测未来的死亡率，因此有望采用新的方法来解决这一问题 对健康衰老及其原因的研究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积累，具有高度可预测性。 表观遗传年龄相对于实际年龄提前，他们的死亡风险增加 这项研究将独立于传统的危险因素来测量参与者的表观遗传年龄。 宿务纵向健康和营养调查跟踪了数千名妇女及其子女 自 1983 年以来。该研究位于菲律宾宿雾市，最近经历了 预期寿命的提高和慢性退行性疾病的社会负担相应增加 这项研究的详细纵向数据将用于解决疾病和晚年功能衰退的问题。 三个目标：1）了解早期生命发育的作用，例如出生尺寸、生长模式和体重 婴儿期和儿童期以及生命早期传染病的进展，作为表观遗传年龄的预测因素 2005 年收集的 DNA 样本库，当时这些人是年轻人（20-22 岁）2) a； 15 年后（2019-20 年）第二个 DNA 样本，并利用这些新数据来研究死亡率的原因 最后，该研究将测量每个人成年期间表观遗传年龄的变化； 2005 年从这些人的母亲处采集的 DNA 样本将 3) 阐明功能域 通过表观遗传年龄预测衰退和晚年疾病，包括死亡率。这项研究具有创新性。 因为它使用两代人收集的详细纵向数据来了解原因和 表观遗传年龄对从出生到老年的整个生命周期的影响。 允许对影响成年早期表观遗传年龄的发育因素进行建模，同时重复成年 相隔 15 年获得的表观遗传年龄测量值将阐明哪些可改变的生活方式因素可预测年龄增长速度 将母亲一代纳入研究将阐明这一生物标志物的能力。 预测最近在这些女性中测量到的功能衰退的具体途径，包括认知、 因此，这项研究将影响记忆力、身体能力、慢性疾病（动脉粥样硬化）和死亡率。 对这种有前途的新衰老生物标志物的效用进行详细评估，同时还 在老年人口迅速增加的人口中促进健康老龄化的启发性战略 人口。