Dominic Withers is Professor of Diabetes and Endocrinology at MRC Clinical Sciences Centre. He has made outstanding contributions to establishing the key role of insulin/insulin-like growth factor signalling (IIS) in mammalian physiology and in the pathophysiology of type 2 diabetes, obesity, and ageing. His studies have given key insights into the mechanisms by which caloric restriction regulates mammalian lifespan implicating AMP-activated protein kinase signalling. This work paves the way for therapeutic strategies to treat the diseases of ageing with currently available agents that act upon such signalling pathways.