Pathways of aging: comparative analysis of gene signatures in replicative senescence and stress induced premature senescence.

摘要: In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it be a consequence external challenges such as oxidative stress. Here we present comparative analysis aimed at reconstruction molecular cascades specific for (RS) and stressinduced (SIPS) human fibroblasts. An involvement caspase-3/keratin-18 pathway serine/threonine kinase Aurora A/ MDM2 was shared between RS SIPS. Moreover, stromelysin/MMP3 N-acetylglucosaminyltransferase enzyme MGAT1, which initiates synthesis hybrid complex Nglycans, were identified key orchestrating components SIPS, respectively. only, Aurora-B driven cell cycle signaling deregulated concert with suppression anabolic branches fatty acids estrogen metabolism. is deprioritized, synthetic cholesterol metabolism are upregulated, rather than downregulated. proteasome/ubiquitin ligase pathways protein degradation dominate regulatory landscape. This picture indicates that SIPS proceeds cells actively fighting stress facilitates premature while failing to completely activate orderly program RS. The promoters genes differentially expressed unusually enriched by binding sites homeobox family proteins, particular emphasis on HMX1, IRX2, HDX HOXC13. Additionally, Iroquois Homeobox 2 (IRX2) master regulator secretion SPP1-encoded osteopontin, stromal driver tumor growth overexpressed both latter supports hypothesis senescence-specific de-repression SPP1 aids SIPS-dependent activation. Reanalysis previously published experimental data cost-effective approach extraction additional insignts into functioning biological systems.