Osteoarthritis is a common condition that affects your joints and is frequently associated with aging. Today, we look at a new open-access paper that discusses the role of aging in the progression of this disease.
So, what is osteoarthritis?
Over time, the surfaces of your joints become worn and damaged, causing them to no longer move as smoothly as they should. Eventually, the cartilage protecting the ends of the bones at the joints gradually thins and eventually wears away, exposing the bone underneath.
This causes the bone to thicken and the tissues in the joint to become more active than normal as the body tries to repair the damage. This leads to the bone at the edge of the joint to grow outwards and form jagged spurs known as osteophytes.
This can cause the synovium (the inner layer of the joint capsule that produces synovial fluid) to thicken and produce excess fluid. The extra fluid can then cause the joint to swell, leading to inflammation and discomfort.
In severe cases, the cartilage can become so thin that the bones grind against each other and wear away. This wearing away of the bone and the formation of spurs can change the shape of a joint and force bones out of position.
Osteoarthritis and oxidative stress
We have talked about osteoarthritis and the role of senescent cells before in a previous article, and a clear link between senescent cell accumulation in joint tissue and the progression of osteoarthritis has been made. Perhaps more importantly, it has been shown that removing these accumulated dysfunctional cells may be beneficial in treating this condition .
The topic of osteoarthritis has appeared again in this new open-access paper . The author of the paper focuses more on the role of oxidative stress rather than the inflammation caused by senescent cells, though the two are closely linked, with one being able to cause the other and vice versa .
Oxidative stress is caused by the excessive creation of reactive oxygen species (ROS) in cells, often by the mitochondria, and it can lead to damage of the cellular machinery or even destroy cells.
More often than not, oxidative stress and inflammation happen together and form a feedback loop, so while this paper focuses on oxidative stress, it offers a slightly different angle on the same large picture.
Mitochondrial dysfunction, cellular senescence, oxidative stress, and inflammation are bound together, and as you read the paper, you will see how interlinked these things are.
This year, Unity Biotechnology is running the first human trials of therapies designed to remove senescent cells, and osteoarthritis is on this company’s target list of diseases to treat, so we will hopefully soon be able to discern how these things interact with each other and to what extent one influences the other.
There are researchers working on the management of oxidative stress and even more ambitious projects such as MitoSENS, which is working to create copies of the mitochondrial genes in the cell nucleus, where they would be shielded from ROS damage. MitoSENS has already successfully moved some of these genes over and could offer a long-term solution to oxidative stress damage.
Also, with senescent cell-removing therapies known as senolytics already showing promising data for osteoarthritis in preclinical testing, there is some room for being optimistic about the potential of this approach in people. Will the results seen in animals translate to humans?
As always in science, the proof of the pudding is in the eating, so let’s find out!
 Jeon, O. H., Kim, C., Laberge, R. M., Demaria, M., Rathod, S., Vasserot, A. P., … & Baker, D. J. (2017). Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature medicine, 23(6), 775-781.
 LOESER, R. F. (2017). The Role of Aging in the Development of Osteoarthritis. Transactions of the American Clinical and Climatological Association, 128, 44.
 Salzano, S., Checconi, P., Hanschmann, E. M., Lillig, C. H., Bowler, L. D., Chan, P., … & Atkuri, K. R. (2014). Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proceedings of the National Academy of Sciences, 111(33), 12157-12162.