Joint Diseases and Senolytic Drugs

The proverb "old age does not come alone" is true all the way down to the cellular level. Aged cells vary from their younger counterparts in that they are trapped in a zombie state of cell cycle arrest, unable to replicate or be naturally suffocated by programmed cell death (apoptosis).

Ageing cells produce a range of pro-inflammatory cytokines, growth factors, proteases, and extracellular matrix components, in addition to changes in genetic stability, energy generation, and cell-to-cell communication, collectively known as "senescence-associated secretory components" (SASPs).

SASPs can be used to stimulate tissue repair and remodelling, but prolonged signalling might cause chronic inflammation, which may contribute to age-related dysfunction.
While the association among cellular senescence as well as particular disease states remains unknown, mechanistic linkages have been suggested to osteoarthritis, and other age-related diseases

What are Senolytics?

Prof. James Kirkland and his Mayo Clinic team have pioneered a novel class of drugs that eradicate senescent cells known as 'senolytics', derived from the terms ‘senescence’ and ‘lytic’ - killing. Senolytics selectively block the pro-survival circuits that safeguard senescent cells from their inherent apoptotic setting by leveraging senescent cells' reliance on certain pro-survival mechanisms, without impacting proliferation or dormant, specialised cells. List of FDA approved senolytics:

1. Tyrosine kinase inhibitor-Dasatinib
2. A flavonoid found in many fruits and vegetables-Quercetin
3. Bcl-2 pro-survival family inhibitor-Navitoclax
4. A flavonoid-Fistein

What is Osteoarthritis (OA)?

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease, affecting more than one-third of the population over the age of 60. OA has a negative influence on quality of life and work capacities in the elderly, and has a substantial impact on health expenses.

The core pathophysiology of OA is articular cartilage degradation, breakdown of the cartilage, a rubbery material that eases the friction in your joints. It can happen in any joint but usually affects your fingers, thumbs, spine, hips, knees, or big toes.

There are systemic risk factors in addition to local risk factors such as obesity and life-related repeated or acute mechanical stressors. The first among these is ageing.
Indeed, the frequency of knee OA rises steadily with age, with the maximum relative risk occurring between the ages of 70 and 75.

Conclusion

Removing senescent cells and inhibiting their accumulation is a powerful anti-ageing approach. Senolytics being the new family of anti-senescence medications that may specifically target and kill senescent cells.

At present there are no recognised curative medicinal therapies for OA. In OA, new symptomatic slow-acting medicines such as glucosamine and visco-supplementation with hyaluronic acid are utilised, although there is at present little proof that they are effective in terms of long-term structural articular remodelling.

As a result, OA continues to be a large unmet demand, with symptomatic painkiller therapies and physiotherapy being the primary alternatives to prosthetic surgical joint replacement.