title: Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan.
abstract: Ageing is defined by the loss of functional reserve over time, leading to a decreased capacity to maintain homeostasis under stress and increased risk of morbidity and mortality. Ageing is extremely heterogeneous between individuals and even between tissues within an organism, making it challenging to identify the molecular basis of ageing. Much of our current understanding of ageing comes from genetic studies in model organisms seeking genes that either accelerate or decelerate the ageing process. These studies revealed not only causes of ageing, but also signaling mechanisms that both promote and protect against ageing. In all cases, the signaling pathways that influence lifespan are familiar mechanisms that regulate cellular metabolism, growth, proliferation, differentiation and survival. This review highlights the significant overlap in signaling mechanisms implicated in both the cellular response to genotoxic stress and regulation of organism lifespan.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA 15213, USA. niedernhoferl@upmc.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: D016328:NF-kappa B; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins