Project description:Senescence is manifested by an increase in oxidative stress and a decline in biological functions with age. In most organisms, body maintenance is traded-off with reproduction. The negative relationship between longevity and fecundity is also evident on the molecular level, yet the proximate mechanisms remain poorly understood. Apparently by-passing this trade-off, social insect queens are both extremely long-lived (up to 30 years in some ants) and highly fecund compared to workers. Here, we study changes in gene expression with age and fecundity in queens to determine how the trade-off between those two traits is reshaped. We analyse tissue-specific gene expression in young founding queens and old, highly fecund queens of the ant Temnothorax rugatulus. More genes altered their expression with age in the fat body than in the brain. Despite strong differences in ovary development, few fecundity genes were differentially expressed. However, many longevity genes involved in well-known pathways or lifespan-associated biological processes changed their expression with age indicating that multiple longevity mechanisms are activated successively throughout a queens’ life. Young queens invested in immunity (i.e. activation of the Toll signalling pathway) and resistance against environmental and physiological stress associated with the founding phase (i.e. down regulation of the TOR pathway), while established older queens up-regulate anti-aging mechanisms (i.e. up-regulation of catalase, superoxide dismutase, heat shock 70 kDa proteins). Finally, we identified a number of candidate genes and pathways, potentially involved in reshaping the fertility-longevity trade-off in social insects, shedding light on how this is achieved on a proximate level.
Project description:Changes in gene regulation have long been though to underlie most phenotypic differences between species. Subterranean rodents, and in particular the naked mole-rat (NMR), have attracted substantial attention due to their proposed phenotypic adaptations, which include hypoxia tolerance, metabolic changes and cancer resistance. However, it is largely unknown what regulatory changes may associate with these phenotypic traits, and whether these are unique to the NMR, the mole-rat clade or also present in other mammals. Here, we undertook a comparative genomics approach to identify genome-wide promoter and enhancer regions harbouring epigenomic hallmarks of regulatory activity, in heart and liver from two mole-rat species (NMR and DMR) and two rodent outgroups. To identify promoters and enhancers displaying robust shifts in regulatory activity in the mole-rat clade, we adapted and applied a phylogenetic modeling approach to quantitatively compare epigenomic signals at orthologous locations, while accounting for phylogenetic distance and inter-species variation. This method identified thousands of orthologous promoter and enhancer regions with increased activity in ancestral or single-species mole-rat branches, as well as hundreds of promoters and enhancers with reduced activity in mole-rats versus other rodents. These elements underlie both shared tissue-specific changes in gene regulation associated with mole-rat evolution, which include metabolic and functional adaptations in heart and liver. Moreover, by comparing mole-rat specific changes in promoters and enhancers between ancestral and single-species branches, our data revealed a number of candidate pathways with stepwise regulatory changes during mole-rat evolution. Lastly, we analysed the genomic properties of non-alignable promoters and enhancers in mole-rats, and report (i) their overlap with specific repetitive elements and transcription factor binding sites; and (ii) their association with metabolic gene functions. On the whole, these comparative analyses reveal mole-rat specific epigenomic changes across orthologous and non-mappable promoters and enhancers - which inform previously reported mole-rat adaptations from a gene regulation perspective.
Project description:We performed RNAseq, metabolomics and pathway enrichment analysis on cardiac tissue from naked mole-rats (Heterocephalus glaber) and from seven other members of African mole rat genera, Cape mole-rat (Georychus capensis), Cape dune mole-rat (Bathyergus suillus), Common mole-rat (Cryptomys hottentotus hottentotus), Natal mole-rat (C. h. natalenesis), Mahali mole rat (C. h. mahali), Highveld mole-rat (C. h. pretoriae) and Damaraland mole-rats (Fukomys damarensis) representing differing burrow and soil types, degrees of sociality, lifespan and hypoxia tolerance. In addition, we include the evolutionarily highly divergent hottentot golden mole (Ambysomus hottentotus), an Afrotherian subterranean, solitary mammal, and the C57/BL6 laboratory mouse as a standard mammal control. After RNA sequencing, we removed the reads mapped to rRNAs and get rawdata, then we filtered the low quality reads (More than 20% of the bases qualities are lower than 10), reads with adaptors and reads with unknown bases (N bases more than 5%) to get the clean reads. These are the data uploaded.
Project description:During the nest-founding phase of the bumble bee colony cycle, queens undergo striking changes in maternal care behavior. Early in the founding phase, prior to the emergence of workers in the nest, queens are reproductive and also provision and feed their offspring. However, later in the founding phase, queens cease feeding offspring and become specialized on reproduction. This transition is synchronized with the emergence of workers in the colony, who assume the task of feeding their siblings. Using a social manipulation experiment, we tested the hypothesis that workers socially regulate the transition from feeding brood to specialization on reproduction in nest-founding bumble bee queens. Consistent with this hypothesis, we found that early-stage queens with workers prematurely added to their nests reduce their brood-feeding behavior and increase egg-laying, and likewise, late-stage queens increase their brood-feeding behavior and decrease egg-laying when workers are removed from their nests. Further, brood-feeding and egg-laying behavior were negatively correlated in these queens. We used an Agilent brain EST-based microarray to explore a second hypothesis, that workers alter brain gene expression in nest-founding queens. We found evidence that brain gene expression in nest-founding queens is altered by the presence of workers, with the effect much stronger in late-stage founding queens. Additionally, expression levels of some genes were correlated with quantitative differences in brood-feeding and egg-laying behavior. This study provides new insights into how the transition from feeding brood to specialization on reproduction in bumble bee queens is regulated during the nest initiation phase of the colony cycle.
Project description:The goal was to find genes which are differentially expressed between the naked mole-rat (Heterocephalus glaber) and the wild-type mice liver tissue. The genes which are most differentially expressed may provide a clue for the remarkable differences between naked mole-rat and mouse in terms of longevity, cancer resistance and adaptation to subterranean environments. Analysis of 2 mRNA samples, one pooled from 3 wild-type mice liver tissue and another pooled from 3 naked mole-rat liver tissue.
Project description:Deep sequencing of mRNA from naked mole rat Analysis of ploy(A)+ RNA of different specimens: brain, kidney, liver from new born , 4 years old , 20 years old and 4 years old hypoxia-exposed naked mole rat
Project description:To study the tumour-suppressive capabilities of naked mole-rat fibroblasts we subcutaneously co-injected the fibroblasts and human squamous carcinoma cells into the flanks of NSG mice, which lack mature T cells. As controls, we (1) performed the co-injection experiment with mouse fibroblasts, and (2) performed experiments in which we injected human squamous carcinoma cells without mouse or naked mole-rat fibroblasts. To determine how the co-injections with mouse or naked mole-rat fibroblasts affected tumour growth in vivo, we then transcriptionally profiled the human skin tumours.
Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan.
Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan