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Oxidative stress

Oxidative stress is the state in which a cell's production of reactive oxygen species outpaces its antioxidant defences, so oxidants start damaging molecules and disturbing the cell's signalling.

Also called oxidant stress, redox imbalance.

A review of cartilage research describes an age-related imbalance in chondrocytes: rising reactive oxygen species against antioxidant capacity that does not keep pace (Bolduc 2019). The harm is not only direct damage. Excess oxidants also disrupt redox-regulated signalling, including the Akt and MAP kinase pathways (Bolduc 2019).

In human cartilage cells from older adults, oxidative stress damaged the peroxiredoxin antioxidants, switched off a survival signal and switched on a death signal (Collins 2016). More than twice as many human cartilage cells from donors aged 50 and over died under oxidant stress as cells from younger donors (Del Carlo 2003).

Mechanical stress adds to it. In rats, mechanical stress led to a build-up of reactive oxygen species in chondrocytes (Kaneko 2019), and in cow cartilage in the lab, repeated compression oxidised glutathione (Zhu 2020). In people it is measured through markers such as malondialdehyde, a by-product of fat oxidation, and the GSH:GSSG ratio (Lizzo 2022).

Sources

  1. Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
  2. 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.
  3. Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
  4. Kaneko Y, Tanigawa N, Sato Y et al. Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. Sci Rep 2019.
  5. 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.
  6. 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.

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Last reviewed 3 November 2026Every study cited here is indexed on PubMed. How we read the evidence