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', 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.
Highlights
Most of our current understanding of the underlying mechanisms of aging comes from short-lived model species
We conducted a multifactorial analysis of differentially expressed genes (DEGs): the analysis was based on the variables reproductive state, sex, and species
Concerning the tested explanatory variables (Fukomys species, sex, breeding status), we found by far the highest number of DEGs at the level of the species comparison
Summary
Most of our current understanding of the underlying mechanisms of aging comes from short-lived model species. It is, still largely unclear to what extent insights obtained from short-lived organisms can be transferred to long-lived species, such as humans (Parker et al, 2004; Keller and Jemielity, 2006). Many studies that involved organisms with long lifespans, for example, queens in social hymenoptera, birds, bats, African mole-rats, and primates, have produced findings that were not always congruent with established aging theories (Keller and Jemielity, 2006; Austad, 2009; Salmon et al, 2009; Austad, 2011; Dammann, 2017; Bens et al, 2018). Many observed differences between species with differing lifespans are influenced by phylogenetic constraints, ecophysiological differences, or both, rather than being causal for the species-specific differences in aging and longevity
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