As our population ages the incidence of Type II diabetes mellitus (T2DM) continues to rise nearly doubling fromthe age of 45 to 65. T2DM is characterized by both hyperinsulinemia and hyperglucagonemia. The majority ofresearch in the metabolic field has focused on the hyperinsulinemia that is characteristic of this disease.However inhibition of glucagon action is highly effective in treating T2DM. In fact metformin the most prescribedanti-diabetic drug activates AMP Kinase (AMPK) to inhibit hepatic glucagon signaling and limit hepatic glucoseproduction in T2DM. Similar to the metabolic field research focused on the accelerated aging in T2DM hasprimarily examined the role of hyperinsulinemia. Interventions and genetic models which decrease insulinsignaling enhance lifespan alter energy metabolism and decrease age-related diseases in the mouse. Despitethe hyperglycemia of T2DM and essential role of glucagon receptor signaling in the long-term survival of the leanaging mouse we lack knowledge of the role glucagon plays in the accelerated aging of obesity or the slowedaging resulting from calorie restriction (CR). The widespread use and development of new therapeutics thatinhibit glucagon signaling to treat T2DM demand studies focused on the role of glucagon signaling in healthyaging. I propose 3 aims focused on the role of global hepatocyte and adipocyte glucagon signaling in metaboliccontrol and progression of aging in lean obese and calorie restricted mice. The studies proposed in this grantwill be the first that investigate the role of glucagon signaling in healthspan assess the response to eliminationof glucagon signaling in either the adipocyte or hepatocyte and address the potential for alternative responsesto glucagon signaling inhibition in obesity normal weight and calorie restriction.