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Cited by 64Sulfur Compounds in BiologyAntioxidant Activity and Oxidative StressGlutathione Transferases and Polymorphisms

Changes in levels of the antioxidant glutathione in brain and blood across the age span of healthy adults: A systematic review

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Detcheverry, Flavie, Senthil, Sneha, Narayanan, Sridar, Badhwar, AmanPreet·2023·NeuroImage: Clinical
DOI 10.1016/j.nicl.2023.103503PMC PMC10520675
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Abstract

Aging is characterized by a gradual decline of the body's biological functions, which can lead to increased production of reactive oxygen species (ROS). Antioxidants neutralize ROS and maintain balance between oxidation and reduction. If ROS production exceeds the ability of antioxidant systems to neutralize, a damaging state of oxidative stress (OS) may exist. The reduced form of glutathione (GSH) is the most abundant antioxidant, and decline of GSH is considered a marker of OS. Our review summarizes the literature on GSH variations with age in healthy adults in brain (in vivo, ex vivo) and blood (plasma, serum), and reliability of in vivo magnetic resonance spectroscopy (MRS) measurement of GSH. A systematic PubMed search identified 35 studies. All in vivo MRS studies (N = 13) reported good to excellent reproducibility of GSH measures. 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. In post-mortem brain, out of 3 studies, 2 reported decreased GSH with age in hippocampal and frontal regions, while 1 study reported increased GSH with age in a frontal region. Oxidized glutathione disulfide (GSSG) was reported to be increased in caudate with age in 1 study, suggesting OS. Although findings in the brain lacked a clear consensus, the majority of studies suggested a decline of GSH with age. The low number of studies (particularly ex vivo) and potential regional differences may have contributed to variability in the findings in brain. In blood, in contrast, GSH levels predominately were reported to decrease with advancing age (except in the oldest-old, who may represent a select group of particularly successful agers), while GSSG findings lacked consensus. The larger number of studies assessing age-specific GSH level changes in blood (N = 16) allowed for more robust consensus across studies than in brain. Overall, the literature suggests that aging is associated with increased OS in brain and body, but the timing and regional distribution of changes in the brain require further study. The contribution of brain OS to brain aging, and the effect of interventions to raise brain GSH levels on decline of brain function, remain understudied. Given that reliable tools to measure brain GSH exist, we hope this paper will serve as a catalyst to stimulate more work in this field.

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  • Contradictory results reported by different groups make an evaluation of the literature on alterations in brain GSH levels in human diseases difficult.

    “However, contradictory results reported by different groups, which may arise in part due to methodological differences, make an evaluation of the literature on alterations in brain GSH levels in human diseases difficult (Bottino et al. 2021; Detcheverry et al. 2023; Rae and Williams 2017).”

    From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Detcheverry et al. 2023

    The Results (Findings in brain; page unavailable) report conflicting findings on age-related brain GSH levels and suggest that differences in tissue preparation may explain one lack of consensus. The review concerns healthy aging, however, and does not establish that conflicting results make it difficult to evaluate brain GSH alterations in human diseases. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Detcheverry, F., Senthil, S., Narayanan, S., & Badhwar, A.
Affiliations
  • Institut Universitaire de Gériatrie de Montréal (CA)
  • Montreal Neurological Institute and Hospital (CA)
Corresponding author
Badhwar, AmanPreet
ORCID
Venue
NeuroImage: Clinical
Publisher
Elsevier BV
Published
2023
Volume
40
Pages
103503
ISSN
2213-1582 (ISSN-L)
DOI
10.1016/j.nicl.2023.103503
PMC
PMC10520675
OpenAlex
W4386157358
Cited by
64
References
1
Citations by year
2026: 24 · 2025: 29 · 2024: 10 · 2023: 1
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Courtois Foundation (19.20)
  • Reseau de Bio-imagerie du Quebec
  • Canadian Institutes of Health Research (153005)
  • Fonds de recherche du Quebec Sante
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
oxidative stress, brain aging, aging, magnetic resonance spectroscopy, glutathione disulfide, blood glutathione, brain glutathione, healthy adults, regional brain differences, oldest old
MeSH terms
Adult, Aged, 80 and over, Antioxidants, Brain, Glutathione, Humans, Reproducibility of Results, Reactive Oxygen Species, Glutathione Disulfide

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