Project description:We compared RNA-seq expression patterns in liver, an organ with high oxidative metabolism and abundant spontaneous DNA damage, from humans, naked mole rats, and mice, differing in maximum lifespan over a range of ~100, 30, and 3 years, respectively, for 130 genes involved in DNA repair. The results show that the longer-lived species, human and naked mole rat, share higher expression of these DNA repair genes, including core genes in several DNA repair pathways. A more systematic approach of signaling pathway analysis (SPA) indicates statistically significant upregulation of several DNA repair signaling pathways in human and naked mole rat compared with mouse.
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: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
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: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: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:Within a cell, proteins are in a dynamic state of turnover and are continuously synthesized and degraded. As an energetically expensive cellular process, protein turnover can have two opposing effects on maintaining a healthy proteome during the lifespan of an organism. Rapid protein turnover can replace old and damaged proteins with newly synthesized proteins. However, the high energetic demands of this process can potentially generate damaging reactive oxygen species that comprise the long-term health of the proteome. Thus, the relationship between aging, protein turnover kinetics and energetic demands of an organism remain unclear. Here, we used a proteomic approach to measure global rates of protein turnover within cultured fibroblasts isolated from a number of species with a wide range of lifespans. We show that organismal lifespan is negatively correlated with global rates of turnover. By further comparing cells from mice and naked mole rats (a short-lived and long-lived rodent species, respectively) we show that the latter has slower rates of turnover, lower levels of ATP production and reduced cellular ROS levels. Despite its slower rate of protein turnover, naked mole rat cells are able to tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive protein turnover, long-lived species such as the naked mole rat have may have evolved more energetically efficient mechanisms for selective clearance of damaged proteins.
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.