Project description:The naked mole rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years. The longevity of the NMR is widely debated, as it poses challenges to theories associated with aging, cancer, and redox homeostasis. In the present study, we report unique mechanisms of cholesterol metabolism in NMR cells that could be responsible in part for their anti-senescent properties. We found that NMR fibroblasts abundantly express β-catenin, and that increased β-catenin activity is linked to increased accumulation of cholesterol-enriched lipid droplets. Either β-catenin knockdown or inhibition of cholesterol synthesis abolished lipid droplet formation, and enhanced induction of senescence-like phenotypes. Analysis of β-catenin-regulated genes revealed that β-catenin upregulated the LXR/RXR pathway and Apolipoprotein F, which are involved in cholesterol biogenesis and transport. Specifically, Apolipoprotein F is involved in the accumulation of lipid droplets, protecting NMR cells from cellular senescence. We thus suggest that increased β-catenin activity evolved in NMRs to offset senescence via the accumulation of cholesterol-enriched lipid droplets. Hence, the anti-senescence effects of the Wnt/β-catenin signaling in NMRs reveals new strategies for the development of anti-cancer and anti-aging treatments.
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: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 goal of this analysis is to compare the transcriptome profile (RNA-seq) along different developmental ages in the naked mole rat ovary
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:We compared expressions of cancer-related genes (tumor suppressor genes and oncogenes) between homeostatic epidermal keratinocytes from Naked mole-rats and FVB mice. Bulk RNA-seq analyses revealed that homeostatic epidermal keratinocytes in Naked mole-rats maintain high expression of tumor suppressor genes that inhibit cell proliferation and activity of pro-oncogenic Wnt, IGF and Hedgehog signaling pathways, stimulate apoptosis and DNA repair, which is associated with downregulation of several key oncogenes stimulating skin carcinogenesis. In contrast to Naked mole-rats, mouse keratinocytes predominantly express tumor suppressor genes linked to cell adhesion, growth factors signaling, nuclear receptors and transcriptional regulators, as well as show decreased expression of oncogenes driving carcinogenesis outside of the skin.