The antioxidant master switch Nrf2 is lower in older and osteoarthritic cartilage cells
This 2023 lab study in human cartilage cells found Nrf2, the protein that switches on many antioxidant genes, was about 40% lower in cells from older adults and about 50% lower in osteoarthritic cells than in younger cells. Oxidative stress raised Nrf2 nearly fourfold in young cells but did not change it in old ones.
What they did
The researchers took chondrocytes, the cells inside cartilage, from young, older and osteoarthritic human donors and measured Nrf2 (nuclear factor erythroid-2-related factor 2) at the protein and gene level.
They exposed cells to menadione, a chemical that generates oxidants, turned Nrf2 down with a gene-silencing tool, or turned it up with a drug called RTA-408. They then measured antioxidant proteins controlled by Nrf2, an inflammatory signal called p65, and how well the cells responded to IGF-1, a growth factor that tells cartilage cells to build matrix.
What they found
Nrf2 protein was significantly lower in older adult cells (about 0.59 times the level in young cells) and in osteoarthritic cells (about 0.50 times). Menadione raised Nrf2 just under fourfold in young cells but did not change it in old cells.
Turning Nrf2 down or up changed levels of antioxidant proteins including sulfiredoxin and NQO1. In osteoarthritic cells treated with IGF-1, activating Nrf2 with RTA-408 lowered p65 activation, raised the gene activity of aggrecan and type II collagen, two main building blocks of cartilage, and increased production of proteoglycans.
What it can't tell us
These were cells in a dish, and the abstract does not give the number of donors or the doses used. RTA-408 is a drug tool used to switch Nrf2 on in the lab, so the result does not show that any food or supplement would do the same. The abstract does not report glutathione measurements.
Why it matters
Nrf2 is one of the main controls on the cell's antioxidant defences. A separate review in this library (Lu 2013) lists Nrf2 among the factors that regulate the genes for glutathione-making enzymes. This study shows that older cartilage cells start with less Nrf2 and fail to raise it when stressed, which offers one explanation for why their defences fall behind.
The paper
- Taylor EL, Collins JA, Gopalakrishnan P et al. Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes. Osteoarthritis Cartilage 2023.
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