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

Sexual activity and/or reproduction are associated with a doubling of life expectancy in the long-lived rodent genus . 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 h...

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Published in:	eLife Vol. 10
Main Authors:	Sahm, Arne, Platzer, Matthias, Koch, Philipp, Henning, Yoshiyuki, Bens, Martin, Groth, Marco, Burda, Hynek, Begall, Sabine, Ting, Saskia, Goetz, Moritz, Van Daele, Paul, Staniszewska, Magdalena, Klose, Jasmin Mona, Costa, Pedro Fragoso, Hoffmann, Steve, Szafranski, Karol, Dammann, Philip
Format:	Journal Article
Language:	English
Published:	England eLife Sciences Publications Ltd 16-03-2021 eLife Sciences Publications, Ltd
Subjects:	ACTHR Adrenal glands Aging Animal reproduction Chromosomes and Gene Expression Computational and Systems Biology Dehydroepiandrosterone DHEA differential gene expression Fukomys Gene expression Growth hormones Hypothalamic-pituitary-adrenal axis Hypothalamus Insulin Life span lifespan Molecular modelling Organisms Oxidative stress Pituitary Proteasomes Sexes Transcription DHEA computational biology systems biology hypothalamic-pituitary-adrenal axis differential gene expression lifespan Fukomys chromosomes gene expression ACTHR
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Summary:	Sexual activity and/or reproduction are associated with a doubling of life expectancy in the long-lived rodent genus . 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.57843