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

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study

“…The body’s stress system mediates the stress response, among which, neuroendocrine hormones including corticotropin-releasing hormone in the HPA axis play an important role in the regulation of basal homeostasis and response to threats, and are involved in the pathogenesis of metabolic diseases [ 17 ]. The HPA axis is believe to be closely related to body growth and development, and its regulatory changes play a key role in life extension [ 18 ]. A lower HPA axis activity has been shown to be a characteristic of long-lived families [ 19 ].…”

Plasma oxidative stress in reproduction of two eusocial African mole-rat species, the naked mole-rat and the Damaraland mole-rat

“…Apart from reproductive division of labour, cooperative care of the young and overlap of generations, the lifetime reproductive success (LRS) among members of both NMR and DMR colonies squarely places these two species on the eusocial end of the eusociality spectrum (see Sherman et al [37]). The remaining colony members (non-breeding females-NBFs and non-breeding males-NBMs) are reproductively quiescent [36], where both NBFs and NBMs can reproduce, but are naturally reproductively suppressed through both behavioural and physiological mechanisms [36,[38][39][40][41][42]. The consequences of this suppression are that reproductive hormones, such as oestrogen, progesterone and testosterone, are significantly higher in the breeding colony members than those of non-breeding colony members [43].…”

“…The non-breeding colony members' reproductive hormones and gonad development are comparable to juvenile (sexually immature) anovulatory colony members [36]. As with eusocial insects, female reproducing members in NMRs and DMRs as well as Ansells (Fukomys anselli) and Giant (Fukomys mechowii) mole-rats colonies are often the longest-lived [34,41,[44][45][46]. However, to date, due to a lack of empirical data pertaining to LRS for F. anselli and F. mechowii they do not fit the stricter conditions for the claim of eusociality according to the definition of Sherman et al [37], which is bimodality, resulting in a high reproductive skew among breeding females and/or males where maximum lifetime fecundity of breeders versus non-breeders (helpers) is far greater than that of female breeders versus helpers in cooperatively breeding vertebrate societies.…”

Stress in an underground empire

“…Breeding females appear to be somewhat shielded from ageing by their reproductive activity and have, for example, lower oxidative damage than non-breeders [40]. In addition, Bens et al [41] identified transcriptome patterns that could contribute to the breeders' long life and good health, and Sahm et al [42] recently found that the HPA axis plays a role in the extended lifespan of the breeders. Nevertheless, high glucocorticoid concentrations could contribute to the low lifeexpectancy of non-breeders [36] considering the detrimental effects of chronic stress [43].…”

“…[ 41 ] identified transcriptome patterns that could contribute to the breeders' long life and good health, and Sahm et al . [ 42 ] recently found that the HPA axis plays a role in the extended lifespan of the breeders. Nevertheless, high glucocorticoid concentrations could contribute to the low life-expectancy of non-breeders [ 36 ] considering the detrimental effects of chronic stress [ 43 ].…”