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.

Comparative analysis of signaling pathways in peripheral blood from patients with Kashin-Beck disease and osteoarthritis

“…NF-κB transcription factor has an important role in the cell response to damage, stress and inflammation (27). In addition, it has been associated with tissue damage, stress, cell differentiation and apoptosis (27)(28)(29). The pathological activation of NF-κB signaling pathway is involved in various inflammatory and rheumatic diseases, including OA and RA (30).…”

The Role of Transcription Factors Dfoxo, Dsir2 and Hsp70 in Lifespan Alteration of Drosophila Melanogaster in Different Light Conditions

“…Гены сиртуинов играют ключевую роль в регуляции скорости старения и долголетия. В частности, повсеместное подавление экс-прессии dSir2 и двух dSir2-подобных генов (CG5085 и CG6284) методом интерференции РНК в нейронах дро-зофил снижает ПЖ, а увеличение активности сиртуинов у дрожжей, червей или мух значительно продлевает ПЖ (Kusama et al, 2006;Li et al, 2008;Niedernhofer et al, 2008;Russell, Kahn, 2007). Существенное снижение МеПЖ на свету происходит и у линий с мутациями в генах семейства Hsp70.…”

Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

“…48 In addition, p53 also inhibits the expression of insulin and IGF1 receptors, while increasing the expression of IGFBP-3, all of which dampen insulin/ IGF1 signaling. 49 Furthermore, p53 is able to diminish the activity of mTORC1 following genotoxic stress; thus, p53-mediated cell cycle arrest remains reversible as long as p53 inhibits mTORC1. [50][51][52][53][54][55] These endocrine responses seem to be highly conserved mechanism, which is likely evolved to cope with stress, and conserve energy resources for maintenance and repair rather than utilizing them for proliferation and growth 30,49 (Fig.…”