The skin of the naked mole-rat and its resilience against aging and cancer

The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words epsilon tau epsilon rho omicron sigma, heteros = divergent, kappa epsilon phi alpha lambda eta, kephale = head and glabra = hairless) was first described by Ruppell (Fig. 1) and belongs to the Hystricognath (from the Greek words upsilon sigma tau rho iota xi, hystrix = porcupine and gamma nu alpha theta omicron sigma, gnathos = jaw) as a suborder of rodents. NMR are characterized by the highest longevity among rodents and reveal a profound cancer resistance. Details of its skin-specific protective and resistance mechanisms against aging and carcinogenesis have so far not been adequately characterized. Recently, our knowledge of NMR skin biology was complemented and expanded by published data using state-of-the art histological and molecular techniques. Here we review and integrate novel published data regarding skin morphology and histology of the aging NMR and the underlying mechanisms at the cellular and molecular level. We relate this data to the longevity of the NMR and its resistance to neoplastic transformation and discuss further open questions to understand its extraordinary longevity. In addition, we will address the exposome, defined as "the total of all non-genetic, endogenous and exogenous environmental influences" on the skin, respiratory tract, stomach, and intestine. Finally, we will discuss in perspective further intriguing possibilities arising from the interaction of skin with other organs.