Extending lifespan by modulating the growth hormone/insulin-like growth factor-1 axis: coming of age.

Progress made in the years of aging research have allowed the opportunity to explore potential interventions to slow aging and extend healthy lifespan. Studies performed in yeast, worms, flies and mice subjected to genetic and pharmacological interventions have given insight into the cellular and molecular mechanisms associated with longevity. Furthermore, it is now possible to effectively modulate pathways that slow aging at different stages of life (early life or at an adult age). Interestingly, interventions that extend longevity in adult mice have had sex-specific success, suggesting a potential link between particular pathways that modulate aging and sex. For example, reduction of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis at an adult age extends lifespan preferentially in females. Moreover, several postnatal dietary interventions tested by the 'Intervention Testing Program (ITP)' from the National Institute of Aging (NIA) have shown that while pharmacological interventions like rapamycin affect the IGF-1/insulin pathway and preferentially extend lifespan in females; dietary compounds that target other cellular pathways are effective only in male mice-indicating mutually exclusive sex-specific pathways. Therefore, a combination of interventions that target non-overlapping aging-related pathways appears to be an effective approach to further extend healthy lifespan in both sexes. Here, we review the germline and postnatal mouse lines that target the GH/IGF-1 axis as a mechanism to extend longevity as well as the dietary compounds that tested positive in the NIA program to increase lifespan. We believe that the interventions reviewed in this paper could constitute feasible combinations for an extended healthy lifespan in both male and female mice.