Obesity and Longevity Across Generations

父母和早期生活因素的分布变化是否改变了肥胖和寿命之间的关系？ 美国日益增长的肥胖率是否会逆转美国人近期预期寿命的增长？是什么让 有些人比其他人更容易受到肥胖缩短寿命的影响？回答这些问题 这些问题需要更好地理解肥胖和长寿之间的复杂关系；尤其是， 早期环境及相关发育因素对环境的潜在调节作用 肥胖和长寿之间的联系。 我们测试了四个相互关联的假设，即人口统计学如何改变体重指数的分布。 (BMI)可能会影响当前一代人的寿命，并改变肥胖对未来寿命的影响 几代人。这些假设是建立在实验模式生物和人类的研究结果基础上的。 来自进化生物学和社会学的流行病学、生活史和发育可塑性理论 了解代际变化和肥胖污名的健康后果的框架。 依靠大量、丰富和互补的次要数据集，我们将完成以下工作 目标：目标1-检验以下假设：相对BMI在一代人或队列BMI分布中的位置 预测长寿超过一个人的绝对体重指数。目标2-测试以下各项假设 与后代发育和BMI相关的因素-父母BMI，肥胖的后代基因组风险分数 (BMIGP)和家庭常见的肥胖环境风险，产生跨代影响并预测(和 因此，与后代体重指数无关的后代死亡率也会受到可信的影响。目标3-检验假设 对于给定的肥胖水平，后代的生理倾向与实际情况之间的“不匹配” 在其他条件相同的情况下，后代肥胖将与寿命下降有关。这一假说是基于 适应性发育可塑性的概念，即个体在发育过程中可能在生理上被“校准” 早期发育，以达到预期的晚年表型的最佳功能和寿命 由它们在早期发育过程中的环境和遗传易感性决定。目标4--估计 调整父母BMI、子代出生体重和子代BMIGP分布的变化 解释了过去半个世纪发生的体重指数与长寿关系的长期变化。 一个由统计学家、老年研究人员、肥胖研究人员、社会学家、遗传学家和 进化和生殖生物学家已经为这项工作精心召集了起来。了解如何和 为什么肥胖与寿命缩短有关，以及谁最容易受到其健康风险的影响，这对 为公共政策提供信息并预测人口健康需求。此外，识别早期生活特征 而加剧肥胖对健康和寿命影响的环境条件对于确定 生物医学或行为预防干预最有效的关键时期和人群。

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.