eLife (Mar 2021)

Increased longevity due to sexual activity in mole-rats is associated with transcriptional changes in the HPA stress axis

  • Arne Sahm,
  • Matthias Platzer,
  • Philipp Koch,
  • Yoshiyuki Henning,
  • Martin Bens,
  • Marco Groth,
  • Hynek Burda,
  • Sabine Begall,
  • Saskia Ting,
  • Moritz Goetz,
  • Paul Van Daele,
  • Magdalena Staniszewska,
  • Jasmin Mona Klose,
  • Pedro Fragoso Costa,
  • Steve Hoffmann,
  • Karol Szafranski,
  • Philip Dammann

DOI
https://doi.org/10.7554/eLife.57843
Journal volume & issue
Vol. 10

Abstract

Read online

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.

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