Birth Weight Predicts Aging Trajectory: A Hypothesis

Increasing evidence suggests that risk for age-related disease and longevity can be programmed early in life. In human populations, convincing evidence has been accumulated indicating that intrauterine growth restriction (IUGR) resulting in low birth weight (<2.5 kg) followed by postnatal catch-up growth is associated with various aspects of metabolic syndrome, type 2 diabetes and cardiovascular disease in adulthood. Fetal macrosomia (birth weight > 4.5 kg), by contrast, is associated with high risk of non-diabetic obesity and cancers in later life. Developmental modification of epigenetic patterns is considered to be a central mechanism in determining such developmentally programmed phenotypes. Growth hormone/insulin-like growth factor (GH/IGF) axis is likely a key driver of these processes. In this review, evidence is discussed that suggests that different aging trajectories can be realized depending on developmentally programmed life-course dynamics of IGF-1. In this hypothetical scenario, IUGR-induced deficit of IGF-1 causes "diabetic" aging trajectory associated with various metabolic disorders in adulthood, while fetal macrosomia-induced excessive levels of IGF-1 lead to "cancerous" aging trajectory. If the above reasoning is correct, then both low and high birth weights are predictors of short life expectancy, while the normal birth weight is a predictor of "normal" aging and maximum longevity.