Project description:Naked mole rats (NMRs, Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span for >30 years. We report application of RNAseq technology to analyze changes in the skin transcriptome of NMRs during aging. RNAseq analyses reveal that the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor genes (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) are increased in aged versus young NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.
Project description:Naked mole-rats are a mammalian model organism of exceptional longevity. We mapped the T cell developmental landscape in Naked mole-rats and showed
Project description:The naked mole-rat, Heterocephalus glaber (NMR), the longest-lived rodent with a maximum possible lifespan exceeding 33 years, is emerging as an important non-model organism for the study of longevity and healthspan. As such it is of significance and interest in the study of biomarkers for ageing in mammals. Recent breakthroughs in this field have indicated that ‘epigenetic clocks’ based on the temporal accumulation of DNA methylation at specific genomic sites can enable accurate age estimates for tissues across the lifespan of an individual. Here, we validate the hypothesis of an epigenetic clock in NMRs, and create a method for predicting the age of naked mole-rats based on changes in methylation of targeted CpG sites in regions known as ageing-associated differentially methylated positions (aDMPs). In the discovery phase, we performed a targeted analysis of 51 different CpGs in 24 different NMR livers spanning an age range from 39 weeks to 1,144 weeks. Of these 51 different sites, 23 were found to be significantly associated with age (p < 0.05). We then built a predictor of age using the 23 sites that showed an association with age. To test the accuracy of this model, we predicted age in an additional test set of 19 different livers spanning an age range 43 to 1,196 weeks. Our model was able to successfully predict age in the test with a root mean squared error (RMSE) of 166.11 weeks. We also profiled a 20 skin samples with the same age range and found a striking correlation between the predicted age of these samples versus their actual age (R=0.93). However, this correlation when compared to the liver samples showed a lower predicted age than actual age, suggesting that skin tissue ages slower than the liver in NMRs. Finally, we have produced freely available software tool that will take in raw sequencing data and produce an age prediction for new NMR samples. Our model will enable the prediction of age in wild caught naked mole-rats and captive animals of unknown age, and will be invaluable for further mechanistic studies of mammalian ageing.
Project description:Performing large-scale plasma proteome profiling is challenging due to limitations imposed by lengthy preparation and instrument time. We present a fully Automated Multiplexed Proteome Profiling Platform (AutoMP3) using the Hamilton VantageTM liquid handling robot capable of preparing hundreds to thousands of samples. To maximize protein depth in single shot runs we combined 16plex Tandem Mass Tags (TMTpro) with high-field asymmetric waveform ion mobility spectrometry (FAIMS Pro) and real-time search (RTS). We quantified over 40 proteins / min / sample, doubling the previously published rates. We applied AutoMP3 to investigate the naked mole-rat plasma proteome both as a function of circadian cycle and in response to ultraviolet (UV) treatment. In keeping with the lack of synchronized circadian rhythms in naked mole-rats, we find few circadian patterns in plasma proteins over the course of 48hr. Furthermore, we quantify many disparate changes between mice and naked mole-rats at both 48hr and one week after UV exposure. These species differences in plasma protein temporal responses could contribute to the pronounced cancer resistance observed in naked mole-rats.
Project description:Heathly naked mole-rats kept under normal housing conditions harbor either a small or enlarged spleen. The aim of the study is to compare RNAseq of naked mole-rat (NM-R) small and enlarged spleens between them and to compare them with RNAseq of mouse spleen.
Project description:Naked mole-rats are a mammalian model organism of exceptional longevity. We mapped the hematopoietic hierarchy and used functional characterizations to define a purified stem and progenitor cell (HSPC) compartment similar to mouse LIN-/Sca-1+/Kit+ HSPCs or human LIN-/CD34+/CD38lo HSPCs.
Project description:Naked mole-rats are a mammalian model organism of exceptional longevity. We mapped the hematopoietic hierarchy and used functional characterizations to define a purified stem and progenitor cell (HSPC) compartment similar to mouse LIN-/Sca-1+/Kit+ HSPCs or human LIN-/CD34+/CD38lo HSPCs.
Project description:We generated single cell transcriptomes from full thickness skin biopsies in naked mole-rat to quantify the skin cell types found in this species (control samples). To study if and how naked mole-rat skin changes upon exposure to a carcinogen, we performed a classical two-stage skin carcinogenesis experiment traditionally performed in mice, wherein cancer is initiated by a single application of 7,12-dimethylbenz[a]-anthracene (DMBA) followed by repeated treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) to drive cell proliferation. After 12 weeks, full thickness skin biopsies were collected and used to generate single cell transcriptomes (treatment samples).