Cartilage cells from donors over 50 died more readily under oxidant stress
This 2003 lab study used human cartilage cells from younger and older tissue donors. More than twice as many cells from donors aged 50 and over died after an oxidant challenge, and the older cells held a larger share of their glutathione in its used, oxidised form. Cells drained of glutathione died more easily.
What they did
The researchers took chondrocytes, the cells inside cartilage, from the joint cartilage of adult tissue donors aged 18 to 49 and 50 and over. They grew the cells in small gel beads and exposed them to SIN-1, a chemical that releases peroxynitrite, a strong oxidant. They counted how many cells died.
They also measured reduced glutathione (GSH, the working form) and oxidised glutathione (GSSG, the used form), tested the activity of several antioxidant enzymes, and drained some cells of glutathione, either with a drug that blocks its production or by removing cystine, a raw material for glutathione, from the culture medium.
What they found
After exposure to SIN-1, more than twice as many cells from the older donors died as cells from the younger donors. Pretreating the cells with IGF-1, a growth factor that normally helps cartilage cells survive, did not prevent the deaths.
Cells from older donors had a higher ratio of GSSG to GSH, meaning more of their glutathione was in the used form. The oxidant lowered the activity of glutathione reductase, the enzyme that turns used glutathione back into its working form, and of thioredoxin reductase, but not of catalase. Cells drained of glutathione were more likely to die.
The authors concluded that rising oxidative stress with age makes cartilage cells more vulnerable to oxidant damage by unsettling the glutathione system.
What it can't tell us
These were cells in a dish, not cartilage inside a living knee. The abstract does not say how many donors were studied or how long the cells were exposed to the oxidant. SIN-1 is a laboratory oxidant at one fixed dose, so it stands in for, but is not the same as, the stresses a real joint faces.
The study compares age groups. It does not test whether raising glutathione in older cells would protect them, and it does not look at people.
Why it matters
This is one of the central papers linking age, glutathione and cartilage cell survival. It shows two things side by side: older cartilage cells carry more of their glutathione in the used form, and cells with less glutathione die more readily under oxidant stress. Much of the later work on the ageing cartilage cell's antioxidant defences builds on this result.
The paper
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
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