title: Do glutathione levels decline in aging human brain?
abstract: For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain.
authors: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8; Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: Junchao.tong@camh.ca.
authors: Junchao
authors: J
authors: Tong
authors: The Drug Detection Agency, Auckland, New Zealand.
authors: Paul S
authors: PS
authors: Fitzmaurice
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
authors: Anna
authors: A
authors: Moszczynska
authors: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8; Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors: Katie
authors: K
authors: Mattina
authors: Division of Neuropathology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.
authors: Lee-Cyn
authors: LC
authors: Ang
authors: Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors: Isabelle
authors: I
authors: Boileau
authors: Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, and Faculty of Medicine, University and Post Graduate University of Juntendo, Tokyo, Japan.
authors: Yoshiaki
authors: Y
authors: Furukawa
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors: Napapon
authors: N
authors: Sailasuta
authors: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
authors: Stephen J
authors: SJ
authors: Kish
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D005978:Glutathione
keywords: Aging; Glutathione; Human brain; Oxidative stress; Postmortem