Obesity and Longevity Across Generations

肥胖与几代人的长寿

基本信息

批准号：
10177831
负责人：
DAVID B ALLISON
金额：
$ 27.65万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10177831
关键词：
Adult Affect Aging Animal Model Behavioral Biology Birth Weight Body mass index Characteristics Collection Complex Data Set Development Diabetes Mellitus Elderly Environment Environmental Risk Factor Epidemiology Experimental Models Family Future Future Generations Generations Genetic Predisposition to Disease Genome Health Heart Diseases Human Individual Intervention Lead Life Life Expectancy Longevity Low Birth Weight Infant Modeling Multiple Birth Offspring Obesity Outcome Persons Phenotype Physiological Population Population trends Positioning Attribute Predisposition Prevalence Prevention strategy Public Health Public Policy Research Personnel Risk Societies Sociology Stigmatization Testing Time Weight Work cohort critical period developmental plasticity deviant intergenerational life history mortality multiple datasets obesity risk offspring offspring obesity population health preventive intervention reproductive risk variant social social stigma sociodemographics sociologist stem theories

项目摘要

Are changing distributions of parental and early life factors altering the relation between obesity and longevity? Will the increasing prevalence of obesity in the US reverse recent gains in US life expectancy? What makes some individuals more susceptible to the life-shortening effects of obesity than others? Answering these questions requires a better understanding of the complex relations between obesity and longevity; in particular, the potential for the early environment and related developmental factors to exert powerful modifying effects on the association between obesity and longevity. We test four interrelated hypotheses about how demographic changes in the distribution of body mass index (BMI) may affect the current generation's lifespan and modify obesity's effect on lifespan in subsequent generations. These hypotheses are built on findings from experimental model organisms and human epidemiology, theories of life histories and developmental plasticity from evolutionary biology, and sociologic frameworks for understanding both intergenerational change and the health consequences of obesity's stigma. Relying on a large, rich, and complementary collection of secondary datasets, we will complete the following aims: Aim 1 - Test the hypothesis that relative BMI position in one's generational or cohort BMI distribution predicts longevity above and beyond one's absolute BMI. Aim 2 - Test the hypotheses that each of several factors related to offspring development and BMI—parental BMI, offspring genome risk score for obesity (BMIGP), and family common environment risk for obesity, exert transgenerational effects and predict (and hence plausibly influence) offspring mortality rate independent of offspring BMI. Aim 3 - Test the hypotheses that a “mismatch” between an offspring's physiological predisposition for a given level of obesity and actual offspring obesity will be, all else being equal, associated with decreased longevity. This hypothesis draws on the idea of adaptive developmental plasticity, in which individuals may be physiologically `calibrated' during early development to achieve best function and longevity for a phenotype in later life that would be predicted by their environmental and genetic predisposition during early development. Aim 4 - Estimate the extent to which adjusting for changes in the distributions of parental BMI, offspring birth weight, and offspring BMIGP accounts for secular changes in the BMI-longevity relation that have occurred in the last half century. An interdisciplinary team of statisticians, aging researchers, obesity researchers, sociologists, geneticists, and evolutionary and reproductive biologists has been carefully assembled for this work. Understanding how and why obesity is associated with reduced longevity and who is most vulnerable to its health risks is vital to informing public policies and anticipating population health needs. Further, identifying early life characteristics and environmental conditions which exacerbate obesity's effects on health and longevity is vital to identifying critical periods and populations where biomedical or behavioral preventive interventions can be most effective.

父母和早期生活因素分布的变化是否会改变肥胖与长寿之间的关系？美国日益增长的肥胖率是否会逆转美国预期寿命的近期增长？有些人比其他人更容易受到肥胖缩短寿命的影响？问题需要更好地理解肥胖与长寿之间的复杂关系；早期环境和相关发展因素对孩子发挥强大改变作用的潜力肥胖与长寿之间的关系。我们测试了关于体重指数分布的人口变化如何的四个相互关联的假设（BMI）可能会影响当前一代人的寿命，并改变肥胖对后代寿命的影响这些假设建立在实验模型生物和人类的发现之上流行病学、进化生物学的生命史理论和发育可塑性以及社会学理解代际变化和肥胖耻辱对健康影响的框架。依托大量、丰富、互补的二级数据集，我们将完成以下工作目标：目标 1 - 检验以下假设：BMI 在一代人或队列 BMI 分布中的相对位置预测寿命高于或超过绝对体重指数目标 2 - 检验几个假设。与后代发育和BMI相关的因素——父母BMI、后代肥胖基因组风险评分（BMIGP）和家庭常见的肥胖环境风险，发挥跨代效应并预测（和因此可能影响）后代死亡率，与后代 BMI 无关目标 3 - 检验假设。后代对给定肥胖水平的生理倾向与实际情况之间存在“不匹配” 在其他条件相同的情况下，后代肥胖与寿命缩短有关。适应性发展可塑性的想法，其中个体可以在生理上“校准” 早期发育以实现预期的晚年表型的最佳功能和寿命目标 4 - 估计其在早期发育过程中的环境和遗传倾向。根据父母 BMI、后代出生体重和后代 BMIGP 分布的变化进行调整解释了过去半个世纪发生的体重指数与寿命关系的长期变化。由统计学家、老龄化研究人员、肥胖研究人员、社会学家、遗传学家和进化生物学家和生殖生物学家已经为这项工作精心召集起来，了解如何以及如何进行。为什么肥胖与寿命缩短以及谁最容易受到肥胖的健康风险至关重要为公共政策提供信息并预测人口健康需求。此外，确定早期生命特征。加剧肥胖对健康和寿命影响的环境条件对于识别肥胖至关重要生物医学或行为预防干预措施最有效的关键时期和人群。