The relationship between the naked mole-rat and hyaluronic acid, as mediated by its receptor CD44: A Mini-Review

The life expectancy of the naked mole-rat (Heterocephalus glaber) is longer than that of other rodents. In NMR cells, the hyaluronic acid concentration is at a higher level. The extracellular matrix’s primary constituent is hyaluronic acid, and CD44 and RHMM are the receptors for hyaluronic acid in the cells. Hyaluronan synthases (HAS); HAS1, HAS2, and HAS3 are located in the plasma membrane and produce hyaluronic acid. Moreover, there are six types of hyaluronic degradation enzymes (Hyal-1, Hyal-2, Hyal-3, Hyal-4, and PH-20). Hyaluronic acid is known to have anti-cancerous effects and acts as a double-edged sword promoting cell senescence and protecting against cellular aging at the same time. NMR’s lengthy lifespan may probably be due to the high molecular weight of hyaluronic acid. INK4 isoforms (P16ink4a/b and pALTINK4a/b) and p27kip1 conferring on NMR a 2-way (early and regular respectively) defense mechanism make NMR more resistant to cancer cells than, humans and mice with only regular contact inhibition (regular (p27kip1). This study, therefore, aims to examine the existing molecular interactions within the NMR-HA-CD44 axis and the ability to confer cancer resistance to mammalian cells through INK4 isoforms gene transfer using the CRISPR method. A lot of potential thus exists in studying these relationships and the prospects for answering the yet unknowns in this area.