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In brain, 3 out of 4 MRS studies reported decreased GSH with age, measured in precuneus, cingulate, and occipital regions, while 1 study reported increased GSH with age in frontal and sensorimotor regions

The constitutive activation has been documented in various cancers, including hepatocellular carcinoma, where it promotes chemoresistance, metabolic reprogramming favoring tumor growth, and evasion of apoptosis (78, 79)

Glutathione can prevent cardiac events and heart disease (7) by neutralising the fat oxidation process and free radical activity

Thus, an increase in NRF2 activity, reflected by induction of NRF2 target genes, likely represent an important mechanism mediating the protection seen in GCLM KO mice