Rodent Longevity is not Directly Associated with Glutathione Cycle

The glutathione pathway is a central component of antioxidant defenses and may affect maximum lifespan (MLSP) by modulating oxidative stress. We determined if species differences in this pathway correlate with MLSP, or reflect phylogeny. We compared five rodents with disparate MLSPs: three Phiomorphs (guinea pigs, 8 yrs.; damara mole‐rats, DMRs 15 yrs.; naked mole‐rats, NMRs >28 yrs.) as well as mice (3.5 yrs.) and blind mole‐rats (15 yrs.). We quantified levels of reduced (GSH) and oxidized (GSSG) glutathione, as well as the activities of cytosolic glutathione peroxidase (cGPx), glutathione s‐transferase (GST) and glutathione reductase (GR) in livers of young animals. There was no species difference in GSH or GSSG levels. GR activity was highest in guinea pigs and lowest in DMRs. cGPx level in mice was nearly 10x higher than in other species, and notably 70x higher than in NMRs. GST was inversely correlated with cGPx. Our results imply that the glutathione cycle is regulated independent of phylogeny and species longevity. Instead, this ubiquitous biochemical pathway may act in a species‐specific manner to modulate different cellular processes.