Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan

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. (c) 2007 Elsevier Ltd. All rights reserved.