Is GDF15 important for the anti-aging effects of metformin?

Aging is the leading risk factor for developing many deleterious chronic diseases, such as diabetes, heart disease, cancer, and Alzheimer’s disease. The type 2 diabetes medication metformin has been shown to delay the onset of many age-related diseases in mice and in cross-sectional studies in humans. How metformin exerts beneficial effects in so many tissues, despite acting primarily in the liver, is unknown. Metformin increases the production of a hormone called growth differentiation factor 15 (GDF15) which is upregulated in the blood of aging mice and humans. In animal models, GDF15 effects include a reduction in food intake, body mass, and inflammation. This project will examine whether GDF15 is critical for the anti-aging effects of metformin and whether this involves the GDF15 receptor, by studying mice treated with metformin but lacking GDF15 and the GDF15 receptor.