Glucomannogalactan inhibits senescence by promoting nuclear translocation of NRF2

For a potential resource to improve healthspan, polysaccharides present unique advantages in terms of side effects and long-term use owing to their low cytotoxicity. In this study, we demonstrate that a glucomannogalactan (PGP) derived from Pleurotus geesteranus extends the healthspan of both naturally senescent and therapyinduced senescence (TIS) mice. Daily treatment of naturally senescent mice with PGP resulted in a reduced accumulation of senescent cells and alleviation of senescence-related parameters, including metabolic dysfunction, underlying lesions in multiple organs, and oxidative damage. PGP treatment also attenuated senescence in TIS mice. Furthermore, in an in vitro model of oxidative stress-induced senescence using a human cell line, we discovered that PGP alleviated senescence by promoting the nuclear translocation of NRF2. This study suggests that PGP may extend the healthspan of senescent mice by facilitating the nuclear translocation of NRF2.