TY - JOUR T1 - The HPA stress axis shapes aging rates in long-lived, social mole-rats JF - bioRxiv DO - 10.1101/2020.02.22.961011 SP - 2020.02.22.961011 AU - Arne Sahm AU - Steve Hoffmann AU - Philipp Koch AU - Yoshiyuki Henning AU - Martin Bens AU - Marco Groth AU - Hynek Burda AU - Sabine Begall AU - Saskia Ting AU - Moritz Goetz AU - Paul Van Daele AU - Magdalena Staniszewska AU - Jasmin Klose AU - Pedro Fragoso Costa AU - Matthias Platzer AU - Karol Szafranski AU - Philip Dammann Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/30/2020.02.22.961011.abstract N2 - Sexual activity and/or reproduction doubles life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed a total of 636 RNA-seq samples across 15 tissues. This analysis suggests that the differences in life expectancy between reproductive and non-reproductive mole-rats are mainly caused by critical changes in the regulation of the hypothalamic-pituitary-adrenal stress axis, which we further substantiate with a series of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and several so-called “anti-aging molecules”, such as DHEA, is also linked with enhanced life expectancy. On the other hand, several our results oppose crucial findings in short-lived model organisms. For example, we found the up-regulation of the IGF1/GH axis and several other anabolic processes to be compatible with a considerable lifespan prolongation. These contradictions question the extent to which findings from short-lived species can be transferred to longer-lived ones.AbbreviationsANOVAanalysis of varianceACTHadrenocorticotropic hormoneDAADigital Aging AtlasDEGdifferentially expressed geneDHEADehydroepiandrosteroneFDRfalse discovery rateKEGGKyoto Encyclopedia of Genes and GenomesMSigDBMolecular Signatures Database ER -