Original ContributionDo glutathione levels decline in aging human brain?
Section snippets
1. Introduction
Oxidative stress is considered a hallmark of human aging [1], [2], [3], [4]; accordingly a variety of antioxidants have been avidly sought as possible dietary supplements or therapeutic reagents for the purpose of anti-aging and protection from degenerative aging changes [5], [6]. The antioxidant glutathione (γ-l-glutamyl-l-cysteinylglycine, GSH, the reduced form), which is synthesized de novo by γ-glutamyl cysteine ligase and glutathione synthetase, plays a pivotal role in supporting oxidative
2. Materials and methods
This study was approved by the Centre for Addiction and Mental Health Research Ethics Board. Brain tissues were obtained at necropsy from a total of 74 subjects (male, n=44; female, n=30) who died without evidence of neurological or psychiatric disease (see Table 1 for subject information and known or suspected cause of death) or brain pathology when the fixed half brain was used for neuropathological examination [postmortem interval (PMI, from 3 to 27 h), 12.9±0.8 h, mean±SEM]. The agonal status
3.1. Overall changes of GSH from birth to senescence
Levels of GSH were not significantly correlated with age from infancy (21 h) to 99 years of age in brain regions examined with the exception of a slight negative correlation in the cerebellar cortex (r=−0.30, n=67, p=0.013; see Table 2). One way ANOVA disclosed differences amongst the six subdivided age groups in caudate (F5,64=3.68, p=0.005), frontal cortex (F5,64=6.63, p<0.0001), and cerebellar cortex (F5,61=4.42, p=0.002) but not in occipital cortex (F5,63 =1.00, p=0.43), suggesting
4. Discussion
The main finding of our study is that, in contradistinction to some preclinical animal data, brain levels of GSH did not decline with advancing age from early adulthood to senescence in the human. This suggests that aging might not compromise the glutathione antioxidant system in the adult human brain.
5. Conclusions
We found in autopsied human brain that levels of the major antioxidant GSH were not decreased during adult aging, a finding that might not be predicted based on a somewhat conflicting preclinical literature. Although our observations do suggest that the brain glutathione system is not compromised in the aging adult human, we consider our data to be preliminary and to suffer from the generic limitations inherent in all postmortem brain studies. Although measurement of GSH in living brain is not
Disclosure statement
The authors have no conflicts of interest to disclose.
Acknowledgments
This study was supported in part by the US NIDA/NIH DA07182 (SK), the New Zealand Institute of Environmental Science and Research, Ltd. (PF, SK), and the Centre for Addiction and Mental Health Foundation.
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