Evidence for Senescent Cells to Contribute to Osteoarthritis
One way to demonstrate that senescent cells, whose numbers grow with age, do in fact contribute meaningfully to age-related disease despite making up only a small proportion of tissues, is to add more of them to an animal model via a cell transplant and then see what happens. Researchers here take that approach to show that senescent cells are one of the contributing causes of osteoarthritis. Various studies place the proportion of senescent cells in different tissues in older individuals of different species in a large range from 1% to as much as 20%, with lower numbers being more common. These cells secrete a mix of signals that cause inflammation and changes in the operation of surrounding cells and the structure of the nearby extracellular matrix. At present a couple of startup companies are working on the clinical development of means to clear senescent cells from the body, one of the first forms of rejuvenation therapy to reverse a root cause of aging, so we'll be seeing more of this sort of research in the next few years.
Researchers have reported a causal link between senescent cells - cells that accumulate with age and contribute to frailty and disease - and osteoarthritis in mice. "Osteoarthritis has previously been associated with the accumulation of senescent cells in or near the joints, however, this is the first time there has been evidence of a causal link. Additionally, we have developed a new senescent cell transplantation model that allows us to test whether clearing senescent cells alleviates or delays osteoarthritis."
Using the new model, researchers injected small numbers of senescent and non-senescent cells from ear cartilage into the knee joint area of mice. After tracking the injected cells in the mice for more than 10 days using bioluminescence and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging, they found that the injection of the senescent cells into the knee region caused leg pain, impaired mobility and characteristics of osteoarthritis, including damage to surrounding cartilage, X-ray changes, increased pain and impaired function. "We believe that targeting senescent cells could be a promising way to prevent or alleviate age-related osteoarthritis. While there is more work to be done, these findings are a critical step toward that goal."
Surprised there isn't more comment...this is a very encouraging study that helps confirm that we are on the right track - or at least "a" right track. I wonder what the "blast radius of damage" is? By this I mean, how many adjacent cells are negatively influenced by one or more senescent cells? If 5% of the body's cells are senescent, and the negative influence is a cube function, then the radius does not have to extend very far until the majority of cells in the body are "touched" by a cell that trashes the neighborhood. thoughts anyone?
@David Gobel: I'd perhaps naively expect the range of damage for a single senescent cell to be very local for extracellular matrix damage, and whole-body for inflammatory signaling. I have no real intuition based on my reading of the field as to what the actual answer is, other than it probably does vary widely by component of SASP.
Given that theories on Alzheimers seem to be trending back towards inflammation (given the continuing difficulties with Amyloid Beta and Tau treatments) I've got to wonder if senescent cells don't contribute to this disease in some way?