In older cartilage cells, oxidised antioxidant enzymes switch survival signals off
This 2016 study in human cartilage cells and mice found that cells from older adults had more over-oxidised peroxiredoxins, a family of antioxidant enzymes. That was linked to a weaker survival signal and a stronger death signal. Mice engineered to clear hydrogen peroxide inside their mitochondria developed less age-related osteoarthritis.
What they did
The researchers compared chondrocytes, the cells inside cartilage, from young and older adult humans. They used menadione, a chemical that generates oxidants, to create oxidative stress, and measured over-oxidation of peroxiredoxins 1 to 3 and two signals inside the cell: Akt, which supports survival, and p38, which pushes towards cell death.
They then tested whether adding catalase, an enzyme that breaks down hydrogen peroxide, aimed at the mitochondria, prevented these changes. They did this in cultured human cells and in cartilage from mice bred to carry this extra catalase. They also looked at human cartilage sections and tracked osteoarthritis as the mice aged.
What they found
Cells from older adults had more peroxiredoxin over-oxidation, both at rest and under oxidative stress. Over-oxidation went along with lower Akt survival signalling and higher p38 death signalling. Mitochondrial catalase prevented these changes in human cells and in mouse cartilage.
Over-oxidised peroxiredoxins were also found in cartilage sections from older adults and in osteoarthritic cartilage. The mice with extra mitochondrial catalase developed less age-related osteoarthritis.
What it can't tell us
The human work was in cells and tissue sections, not in living people, and the protective effect on osteoarthritis was seen only in genetically engineered mice. The abstract does not give the number of donors or animals.
The study did not measure glutathione, according to the abstract. It concerns a different antioxidant family, so it cannot say how glutathione levels relate to these signalling changes.
Why it matters
Glutathione is one part of a wider antioxidant network in cartilage cells. This study shows another part of that network, the peroxiredoxins, wearing out with age, and links that to the cell's survival signals. It supports the broader idea that the ageing cartilage cell's antioxidant defences fall behind, and that this matters for whether the cell survives.
The paper
- 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.
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