Approved research

The effects of lifetime IGF-1 exposure on physiological aging in humans

Lay summary

Insulin-like growth factor 1 (IGF-1) is a key regulator of energy utilization and growth in humans. Over 3 decades of work in model organisms has also implicated this hormone in aging. To date, studies of IGF-1 in humans have focused on the effects of hormone levels measured at a single time. In contrast, we hypothesize that the role of IGF-1 in aging is related to its cumulative exposure, just as the risk for lung cancer from smoking is calculated in terms of pack-years of cigarettes. Therefore, we aim to identify genes that predispose certain individuals to have high or low levels of IGF-1 throughout their lives. This may represent an advancement over the use of blood levels from a single time point, which are affected by a number of short-term influences such as recent exercise and fasting. Specifically, this study will (1) perform the largest and most extensive search for genetic determinants of IGF-1 to date, (2) develop methods for combining different types of genetic variants into a holistic measurement of one's genetic predisposition for a trait, and (3) investigate the health effects of having increased or decreased IGF-1 levels. The initial phase of this project is expected to last 18 months. Results from this work may be useful for predicting individuals' predisposition to healthy aging or age-associated disease, and may identify specific diseases for which individuals with high or low levels of IGF-1 may be at increased risk. In addition, a better understanding of the role of IGF-1 in human aging may guide future model animal work to focus on the mechanisms that are most relevant to humans, and may also lead to the development of interventions that can promote healthier aging.