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


Type
Article
Change log
Authors
Fatima, Iqra 
Chen, Guodong 
Botchkareva, Natalia V 
Sharov, Andrey A 
Thornton, Daniel 
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.

Description
Keywords
Animals, Humans, Mice, Genes, Tumor Suppressor, Homeodomain Proteins, Immediate-Early Proteins, Longevity, Matrix Metalloproteinase 11, Matrix Metalloproteinase 9, Mole Rats, Receptors, Cytoplasmic and Nuclear, RNA, Skin Aging, Tumor Suppressor Proteins
Journal Title
J Invest Dermatol
Conference Name
Journal ISSN
0022-202X
1523-1747
Volume Title
142
Publisher
Elsevier BV
Sponsorship
Dunhill Medical Trust (RPGF2002\188)