title: The impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice.
abstract: Over the past 5 years, data collected from the mouse suggest that pathways important for either preventing or resolving DNA damage are longevity assurance mechanisms whose critical overall function is somatic cell maintenance, a necessary part of cancer prevention. These pathways include those that reduce DNA damage levels caused by exogenous sources, replication errors and by-products of cellular respiration. Unresolved DNA damage leads to permanent mutations in the genetic code that may be oncogenic. Therefore, pathways that resolve DNA damage are important anti-cancer mechanisms. As an important line of defense, there are a variety of pathways that repair DNA damage. In addition, there are anti-cancer pathways that respond to DNA damage by either preventing cellular replication or inducing cell death. Genes in these pathways, termed longevity assurance genes (LAG), code for proteins that reduce cancer incidence and as a result assures a sufficiently long health span needed for reproduction. Data from mouse models, many that were originally designed to study cancer, are showing that a potential consequence of DNA damage and responses to DNA damage is aging; these models support the hypothesis that at least some aspects of normal aging are the consequence of anticancer mechanisms designed to deal with damaged DNA.
authors.affiliation: Department of Molecular Medicine, University of Texas, Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA. hastye@uthscsa.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics* / Q000502:physiology; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology