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| Status |
Public on Feb 21, 2021 |
| Title |
Naked mole rat cells are protected from cellular senescence via Wnt/β-catenin-promoted cholesterol metabolism |
| Organism |
Heterocephalus glaber |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
To determine the mechanisms by which β-catenin induced accumulation of cholesterol-enriched lipid droplets, we performed comparative RNA-seq analysis of control and β-catenin knockdown NSFs (Naked mole rats skin fibroblasts).
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| Contributor(s) |
Chee W, Daisuke O, Okada M |
| Citation(s) |
33742113 |
| Submission date |
Apr 01, 2020 |
| Last update date |
Mar 21, 2021 |
| Contact name |
Daisuke Okuzaki |
| E-mail(s) |
dokuzaki@biken.osaka-u.ac.jp
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| Phone |
+81-6-6879-4935
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| Organization name |
Osaka univ.
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| Department |
Immunology Frontier Research Center
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| Lab |
Human Immunology （Single Cell Genomics)
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| Street address |
Yamadaoka 3-1
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| City |
Suita |
| State/province |
Osaka |
| ZIP/Postal code |
565-0871 |
| Country |
Japan |
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| Platforms (1) |
| GPL21195 |
Illumina HiSeq 2500 (Heterocephalus glaber) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA622445 |
| SRA |
SRP254888 |
