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.
-
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.
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.
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.
Metrics
-
- 2,736
- views
-
- 280
- downloads
-
- 22
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Chromosomes and Gene Expression
The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of SIR2, a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.
-
- Chromosomes and Gene Expression
Specialized magnetic beads that bind target proteins to a cryogenic electron microscopy grid make it possible to study the structure of protein complexes from dilute samples.