Sexual activity and/or reproduction are associated with a doubling of life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed 636 RNA-seq samples across 15 tissues. This analysis suggests that changes in the regulation of the hypothalamic-pituitary-adrenal stress axis play a key role regarding the extended life expectancy of reproductive vs. non-reproductive mole-rats. This is substantiated by a corpus of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and so-called 'anti-aging molecules', for example, dehydroepiandrosterone, is linked with enhanced lifespan. On the other hand, several of our results are not consistent with knowledge about aging of short-lived model organisms. For example, we found the up-regulation of the insulin-like growth factor 1/growth hormone 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.

Central Animal Laboratory University Hospital University of Duisburg Essen Essen Germany

Computational Biology Group Leibniz Institute on Aging Fritz Lipmann Institute Jena Germany

Core Facility Life Science Computing Leibniz Institute on Aging Fritz Lipmann Institute Jena Germany

Core Facility Sequencing Leibniz Institute on Aging Fritz Lipmann Institute Jena Germany

Department of Game Management and Wildlife Biology Faculty of Forestry and Wood Sciences Czech University of Life Sciences Prague Czech Republic

Department of General Zoology Faculty of Biology University of Duisburg Essen Essen Germany

Department of Nuclear Medicine University Hospital University of Duisburg Essen Essen Germany

Department of Zoology University of South Bohemia České Budějovice Czech Republic

Institute of Pathology and Neuropathology University Hospital University of Duisburg Essen Essen Germany

Institute of Physiology University Hospital University of Duisburg Essen Essen Germany

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