Increased longevity due to sexual activity in mole-rats is associated with transcriptional changes in HPA stress axis
Abstract
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", e.g. DHEA, 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 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.
Data availability
Read datasets generated during the current study are available in the European Nucleotide Archive, study ID: PRJEB29798.
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Transcriptome signatures of fast vs. slow aging in Fukomys mole-rat breeders vs. non-breedersEuropean Nucleotide Archive, PRJEB29798.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (PL 173/8-1)
- Matthias Platzer
Deutsche Forschungsgemeinschaft (DA 992/3-1)
- Philip Dammann
Deutsche Forschungsgemeinschaft (Research Training Group 1739)
- Magdalena Staniszewska
Wiedenfeld-Stiftung/Stiftung Krebsforschung Duisburg
- Magdalena Staniszewska
Joachim Herz Stiftung
- Arne Sahm
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jing-Dong Jackie Han, Chinese Academy of Sciences, China
Ethics
Animal experimentation: Animal housing and tissue collection were compliant with national and state legislation (breeding allowances 32-2-1180-71/328 and 32-2-11-80-71/345; ethics/animal experimentation approval 84-02.04.2013/A164, Landesamt für Natur-, Umwelt- und Verbraucherschutz Nordrhein-Westfalen). Before sampling, animals were anaesthetized with ketamine combined with xylazine (Garcia Montero et al. 2015). Every effort was made to minimize suffering.
Version history
- Received: April 15, 2020
- Accepted: March 15, 2021
- Accepted Manuscript published: March 16, 2021 (version 1)
- Version of Record published: March 31, 2021 (version 2)
- Version of Record updated: July 21, 2021 (version 3)
Copyright
© 2021, Sahm et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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