Premature Aging and Reduced Cancer Incidence Associated with Body-Wide Loss of Myc

MYC proto-oncogene dysregulation alters metabolic, translational, cell cycle and other functions in ways that support tumor induction and maintenance. Myc+/- mice are healthier and longer-lived 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. Normal aging and its associated cancer predisposition are thus highly linked via Myc and its target genes and can be genetically separated. ### Competing Interest Statement The authors have declared no competing interest.