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bioRxiv · 10.1101/2020.02.22.961011

Status-dependent aging rates in long-lived, social mole-rats are shaped by HPA stress axis

Sahm, A.·Hoffmann, S.·Koch, P.·Henning, Y.·Bens, M.·Groth, M.·Burda, H.·Begall, S.·Ting, S.·Goetz, M.·Van Daele, P.·Staniszewska, M.·Klose, J.·Costa, P. F.·Platzer, M.·Szafranski, K.·Dammann, P.
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Abstract

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.

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Sahm, A., Hoffmann, S., Koch, P., Henning, Y., Bens, M., Groth, M., Burda, H., Begall, S., Ting, S., Goetz, M., Van Daele, P., Staniszewska, M., Klose, J., Costa, P. F., Platzer, M., Szafranski, K., Dammann, P.. 2020-02-23. Status-dependent aging rates in long-lived, social mole-rats are shaped by HPA stress axis. https://doi.org/10.1101/2020.02.22.961011

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