Calorie restriction increases liver 5’AMP kinase (AMPK) activity. Like the glucagon receptor, AMPK is essential for calorie restriction to extend lifespan and healthspan. Because AMPK is downstream of glucagon receptor signaling it is possible that glucagon receptor activated AMPK is necessary for calorie restriction to improve healthspan We propose that glucagon receptor signaling at the liver, which increases with both calorie restriction and obesity, slows aging dependent upon glucagon receptor stimulated AMPK activity. The proposed study will extend our findings from the parent grant to assess the ability to rescue the impaired healthspan in glucagon receptor null mice by inducing hepatocyte expression of a constitutively active AMPK.