Abstract
Naked mole-rats are extremely long-lived rodents with a lifespan of up to 40 years, during which cellular and tissue aging is rarely observed. In this study, we analyzed the extracellular matrix (ECM) of naked mole-rat skin at the molecular level to elucidate the molecules involved in anti-aging and their localization. Raman spectroscopy and Fourier transform infrared spectroscopy were applied to investigate the hierarchical structure of the ECM, showing that, whereas the epidermis of aged mice had thinned, the epidermis of naked mole-rats became thickened and hyaluronic acid (HA) was distributed under the basement membrane. Furthermore, naked mole-rat skin had a regular skin texture and flexibility, allowing the maintenance of a youthful appearance. Hyaluronic acid in naked mole-rats characteristically exists as clusters (chain HA) in skin tissue, where it is thought to permit moisture retention and maintain elasticity, contributing to the skin's youthful appearance. These results suggested that not only the density of ECM but also its spatial distribution and topographic properties are important for skin anti-aging. Our findings may contribute to the elucidation of skin disease pathology, the development of therapeutic gel scaffolds, and the control of aging.