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Platzer, M.

Publications and source records attributed to Platzer, M..

8 recordsLinked to original sources

Non-aging despite high mutation rate - genomic insights into the evolution of Hydra

Hydra is a genus of freshwater polyps with remarkable regeneration abilities and a non-senescent phenotype under laboratory conditions. Thus, this animal is particularly interesting for aging research. Here, we gained insights into Hydras recent genetic evolution by genome sequencing of single cells and whole individuals. Despite its extreme longevity, Hydra does not show a lower somatic mutation rate than humans or mice. While we identify biological processes that have evolved under positive selection in animals kept in optimal laboratory conditions for decades, we found no signs of strong negative selection during this tiny evolutionary window. Interestingly, we observe the opposite pattern for the preceding evolution in the wild over a longer time period. Moreover, we found evidence that Hydra evolution in captivity was accompanied and potentially accelerated by loss of heterozygosity. Processes under positive selection in captive animals include pathways associated with Hydras simple nervous system, its nucleic acid metabolic process, cell migration, and hydrolase activity. Genes associated with organ regeneration, regulation of mRNA splicing, histone ubiquitination, and mitochondrial fusion were identified as highly conserved in the wild. Remarkably, several of the processes under strongest selection are closely related to those considered essential for the exapted, i. e. not brought about by natural selection, feature: Hydras non-aging.

evolutionary biology↗

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↗

Mitohormetic effects of rotenone drastically depend on age

Hormesis refers to a biphasic intensity-dependent response to stressors where low-intensity or short-duration exposure to potentially noxious stressors induces long-lasting adaptations that have positive physiological effects [1]. It was proposed that life-extending interventions, such as calorie restriction, retard aging via their hormetic action [2]. More recently, it was shown that a transient burst of reactive oxygen species is required to induce the effects of calorie restriction [3], physical exercise [4], inhibition of the insulin/IGF-I pathway [5] and metformin [6]. We have previously shown that partial inhibition of complex I of the respiratory chain by a low dose of the poison rotenone (ROT) administered in middle age increases the lifespan and reverts the transcriptomic signature of aging in a vertebrate species [7], an example of a hormetic effect. Here, we asked whether ROT treatment started at young age induces larger effects on life-span and transcriptome.

pharmacology and toxicology↗

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↗

Naked mole-rat transcriptome signatures of socially-suppressed sexual maturation and links of reproduction to aging

Naked mole-rats (NMRs) are eusocially organized in colonies. Although breeders carry the additional metabolic load of reproduction, they are extremely long-lived and remain fertile throughout their lifespan. Comparative transcriptome analysis of ten organs from breeders and non-breeders of the eusocial long-lived NMR and the polygynous shorter-lived guinea pig provide comprehensive and unbiased molecular evidence that sexual maturation in NMR is socially suppressed. After transition into breeders, transcriptomes are markedly sex-specific, show pronounced feedback signaling via gonadal steroids and have similarities to reproductive phenotypes in African cichlid fish. Further, NMRs show functional enrichment of status-related expression differences associated with aging. Lipid metabolism and oxidative phosphorylation - molecular networks known to be linked to aging - were identified among most affected gene sets. Further, a transcriptome pattern associated with longevity is reinforced in NMR breeders contradicting the disposable soma theory of aging and potentially contributing to their exceptional long life- and healthspan.

systems biology↗

Species comparison of liver proteomes reveals enhanced lipid metabolism, reduced mitochondrial respiration and enhanced expression of detoxifying enzymes in the long-lived naked mole-rat.

Mammals display wide range of variation in their lifespan. Investigating the molecular networks that distinguish long-from short-lived species has proven useful to identify determinants of longevity. Here, we compared the liver of long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omic approach. We found that NMRs livers display a unique expression pattern of mitochondrial proteins that result in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, we show that the same molecular networks are affected during aging in both NMR and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we identified a novel longevity pathway and validated it experimentally in the nematode C. elegans.

systems biology↗

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↗

A miRNA catalogue and ncRNA annotation of theshort-living fish Nothobranchius furzeri

Background: The short-lived fish Nothobranchius furzeri is the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age-dependent control of gene expression.\n\nResults: Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) for Nothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of seven Nothobranchius species. Additionally, duplication and clustering of N. furzeri miRNAs was analyzed and compared to the four fish species Danio rerio, Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes. A peculiar characteristic of N. furzeri as compared to other teleosts was a duplication of the miR-29 cluster.\n\nConclusion: The completeness of the catalogue we provide is comparable to that of zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.\n\nAvailability: All supplementary material can be found online at http://www.rna.uni-jena.de/en/supplements/nothobranchius-furzeri-mirnome/.

genomics↗