Obesity and Longevity Across Generations

父母和早期生活因素的变化是否会改变肥胖和长寿之间的关系？

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.