Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid
Open accessAbstract
An extensive body of evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. High levels of oxidative damage results in key cellular changes including a reduction in available nicotinamide adenine dinucleotide (NAD(+)), an essential molecule required for a number of vital cellular processes including DNA repair, immune signaling and epigenetic processing. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24-91 years). CSF was collected from consenting patients who required a spinal tap for the administration of anesthetic. CSF of participants aged >45 years was found to contain increased levels of lipid peroxidation (F2-isoprostanes) (p = 0.04) and inflammation (IL-6) (p = 0.00) and decreased levels of both total antioxidant capacity (p = 0.00) and NAD(H) (p = 0.05), compared to their younger counterparts. A positive association was also observed between plasma [NAD(H)] and CSF NAD(H) levels (p = 0.03). Further analysis of the data identified a relationship between alcohol intake and CSF [NAD(H)] and markers of inflammation. The CSF of participants who consumed >1 standard drink of alcohol per day contained lower levels of NAD(H) compared to those who consumed no alcohol (p<0.05). An increase in CSF IL-6 was observed in participants who reported drinking >0-1 (p<0.05) and >1 (p<0.05) standard alcoholic drinks per day compared to those who did not drink alcohol. Taken together these data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated by alcohol intake.
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Age-related increase in IL-6, oxidative damage, and concurrent reduction in total antioxidant capacity levels was reported in the cerebrospinal fluid of healthy adults.
“Similarly, age-related increase in IL-6, oxidative damage, and concurrent reduction in total antioxidant capacity levels was reported in the cerebrospinal fluid of healthy adults (Guest et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Guest et al, 2014
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- Authors
- Guest, J., Grant, R., Mori, T. A., & Croft, K. D.
- Affiliations
- Sydney Adventist Hospital (AU)
- The University of Sydney (AU)
- The University of Western Australia (AU)
- Corresponding author
- Grant, Ross
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-14
- Volume
- 9
- Issue
- 1
- Pages
- e85335
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3891813
- OpenAlex
- W2012690986
- Cited by
- 66
- References
- 75
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 6
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Bupa Health Foundation
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cerebrospinal fluid, brain aging, oxidative stress, inflammation, NAD(H), lipid peroxidation, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, total antioxidant capacity, interleukin-6, alcohol consumption, neurodegeneration
- MeSH terms
- Adult, Aged, Aging, Alcohol Drinking, Humans, Inflammation, Life Style, Male, Middle Aged, NAD, Sex Characteristics, Biomarkers, Oxidative Stress, Young Adult
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