Deregulation of CRTCs in Aging and Age-Related Disease Risk

Advances in public health in the past century have seen a sharp increase in human life expectancy. With these changes have come an increased prevalence of age-related pathologies and health burdens in the elderly. Patient age is the biggest risk factor for multiple chronic conditions that often occur simultaneously within a single individual. An alternative to disease-centric therapeutic approaches is that of ‘geroscience’, which aims to define molecular mechanisms that link age to overall disease risk. One such mechanism is deregulation of CREB-regulated transcriptional coactivators (CRTCs). Initially identified for their role in modulating CREB transcription, the past 5 years has seen an expansion in knowledge of new cellular regulators and roles of CRTCs beyond CREB. CRTCs have been shown to modulate organismal aging in Caenorhabditis elegans and to impact on age-related diseases in humans. We discuss CRTC deregulation as a new driver of aging that integrates the link between age and disease risk.