Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes

Fatima, Iqra; Chen, Guodong; Botchkareva, Natalia V; Sharov, Andrey A; Thornton, Daniel; Wilkinson, Holly N.; Hardman, Matthew J.; Grutzkau, Andreas; Pedro de Magalhaes, Joao; Seluanov, Andrei; St J Smith, Ewan; Gorbunova, Vera; Mardaryev, Andrei N; Faulkes, Chris G; Botchkarev, Vladimir A

Abstract

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 >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs. We show that similar to aging in human skin, aging in NMRs is accompanied by a decrease in epidermal thickness; keratinocyte proliferation; and a decline in the number of Merkel cells, T cells, antigen-presenting cells, and melanocytes. Similar to that in human skin aging, expression levels of dermal collagens are decreased, whereas matrix metalloproteinase 9 and matrix metalloproteinase 11 levels increased in aged versus in young NMR skin. RNA-sequencing analyses reveal that in contrast to human or mouse skin aging, the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) genes are increased in aged 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.

Citation

Fatima, I., Chen, G., Botchkareva, N. V., Sharov, A. A., Thornton, D., Wilkinson, H. N., …Botchkarev, V. A. (in press). Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes. Journal of Investigative Dermatology, https://doi.org/10.1016/j.jid.2022.04.028

• Journal Article Type: Article
• Acceptance Date: Apr 26, 2022
• Online Publication Date: Jun 9, 2022
• Deposit Date: May 1, 2022
• Publicly Available Date: Jun 10, 2023
• Journal: Journal of Investigative Dermatology
• Print ISSN: 0022-202x
• Electronic ISSN: 1523-1747
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.jid.2022.04.028
• Public URL: https://hull-repository.worktribe.com/output/3986690