What happens to cartilage glutathione with age?
With age, cartilage cells tend to hold more of their glutathione in its used, oxidised form and cope worse with oxidative stress. In human cartilage cells, more than twice as many cells from donors aged 50 and over died under oxidant stress as cells from donors aged 18 to 49 (Del Carlo 2003), and in rats cartilage glutathione was more susceptible to age-related oxidation than other joint tissues (Zhu 2020).
Older cells, more oxidised glutathione
The clearest human data come from a 2003 study of chondrocytes taken from tissue donors. Cells from donors aged 50 and over had a higher ratio of oxidised to reduced glutathione, and more than twice as many of them died after exposure to an oxidant. Adding the growth factor IGF-1 did not prevent the deaths (Del Carlo 2003).
In rats, 30-month-old animals showed more glutathione oxidation in cartilage than in the meniscus or fat pad of the same knee (Zhu 2020).
The defences around it weaken too
Nrf2, the switch that turns on a cell's antioxidant genes, was about 40% lower in cartilage cells from older adults and about 50% lower in osteoarthritic cells than in cells from younger adults. When stressed, young cells raised their Nrf2 nearly fourfold; old cells did not (Taylor 2023).
Older human chondrocytes also showed more oxidative damage to peroxiredoxins, another family of antioxidant enzymes. That damage switched off a survival signal and switched on a death signal, and mice protected from mitochondrial oxidants developed less age-related osteoarthritis (Collins 2016). A 2019 review describes the overall picture as an age-related imbalance between oxidant production and the cell's antioxidant capacity (Bolduc 2019).
The same pattern shows up in blood
Whole-body studies point the same way. Older adults had lower red-cell glutathione, glycine and cysteine and made glutathione more slowly than younger adults (Sekhar 2011). In 114 healthy adults with an average age of 65, the ratio of reduced to oxidised glutathione in blood was lower than in a young reference group (Lizzo 2022).
Other questions people ask
At what age does it change?
The 2003 human study compared donors aged 18 to 49 with donors aged 50 and over (Del Carlo 2003). It shows a difference between those groups, not a precise age when change begins.
Can older cartilage cells still raise their glutathione?
In a mouse cell study, a pro-oxidant challenge made cells raise both their glutathione and their GSH:GSSG ratio, but recovery was slower when a protective enzyme, Sirt3, was missing (Zhu 2020). In older people, supplying cysteine and glycine raised blood glutathione (Sekhar 2011; Kumar 2023).
Sources
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- Zhu S, Makosa D, Miller B et al. Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connect Tissue Res 2020.
- Taylor EL, Collins JA, Gopalakrishnan P et al. Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes. Osteoarthritis Cartilage 2023.
- Collins JA, Wood ST, Nelson KJ et al. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes. J Biol Chem 2016.
- Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
- Sekhar RV, Patel SG, Guthikonda AP et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011.
- Lizzo G, Migliavacca E, Lamers D et al. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging 2022.
- Kumar P, Liu C, Suliburk J et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci 2023.
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