Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation

Deregulation of the MYC proto-oncogene alters metabolic, translational, cell cycle and other functions in ways that are conducive to tumor induction and maintenance. Myc+/- mice are healthier and age slower than control mice but the long-term ramifications of more complete Myc loss remain unknown. We now describe the life-long consequences of body-wide Myc inactivation initiated post-natally. “MycKO” mice rapidly acquire numerous features of premature aging including altered body composition and habitus, metabolic dysfunction, hepatic steatosis and the dysregulation of numerous gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have an extended life span that correlates with a 4-5-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans deregulate many of the same gene sets as do young MycKO mice while also down-regulating Myc and many of its target genes. Aging and its associated cancer predisposition are thus highly coupled via Myc and can be genetically separated. Comparative gene expression profiling analysis of RNA-seq data for MycKO and WT in 5 month and 20 month old mice's omental adipose tissue, liver and skeletal muscle .