Biology subjects

Dammann, P.

Publications and source records attributed to Dammann, P..

3 recordsLinked to original sources

bioRxiv2020

Status-dependent aging rates in long-lived, social mole-rats are shaped by HPA stress axis

Sexual activity and/or reproduction doubles life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed a total of 636 RNA-seq samples across 15 tissues. This analysis suggests that the differences in life expectancy between reproductive and non-reproductive mole-rats are mainly caused by critical changes in the regulation of the hypothalamic-pituitary-adrenal stress axis, which we further substantiate with a series of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and several so-called "anti-aging molecules", such as DHEA, is also linked with enhanced life expectancy. On the other hand, several our results oppose crucial findings in 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.

genomics↗

bioRxiv2018

Higher transcriptome stability during aging in long-lived giant mole-rats compared to short-lived rats

Many aging-associated physiological changes are known to come up in short- and long-lived species with a different trajectory and emerging evidence suggests that large parts of life history trait differences between species are based on inter-species variation in gene expression. Little information is yet available, however, about transcriptome changes during aging when comparing mammals with different lifespans. For this reason, we studied the transcriptomes of five tissues and two age cohorts in two similar sized rodent species with very different lifespans: rat (Rattus norvegicus) and giant mole-rat (Fukomys mechowii) with maximum lifespans of 3.8 and >20 years, respectively. Our results show that giant mole-rats exhibit higher transcriptome stability during aging than the rat. While well-known aging signatures (e.g. up-regulation of pro-inflammatory genes) were detected in all rat tissues, they showed up only in one giant mole-rat tissue. Furthermore, many differentially expressed genes that were found in both species, were regulated in opposite directions during aging. This suggests that expression changes that cause aging in short-lived species are counteracted in long-lived species. Taken together, transcriptome stability may be one key causal factor of the long life- and healthspan of giant mole-rats and maybe of African mole-rats in general.

systems biology↗

bioRxiv2017

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality

The genetic mechanisms that determine lifespan are poorly understood. Most research has been done on short lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. We obtained genomic and transcriptomic data from 17 rodent species and systematically scanned eleven lineages associated with the evolution of longevity and eusociality for positively selected genes (PSGs). The set of 319 PSGs contains regulators of mTOR and is enriched in functional terms associated with (i) processes that are regulated by the mTOR pathway, e.g. translation, autophagy and mitochondrial biogenesis, (ii) the immune system and (iii) antioxidant defense. Analyzing gene expression of PSGs during aging in the long-lived naked mole-rat and up-regulation in the short-lived rat, we found a pattern fitting the antagonistic pleiotropy theory of aging.

evolutionary biology↗