Introduction
Osteoarthritis (OA) is a frequently occurring joint disease, especially in people aged above 60 years. While younger individuals can also develop OA after joint injuries, aging still remains to be the major risk factor. Osteoarthritis is characterized by changes in the joints, including inflammation of the synovium (joint lining), cartilage breakdown, subchondral bone alterations (bone changes beneath the cartilage), and ongoing joint pain. This pain usually results in difficulty moving and affects the overall quality of life. It has been debated whether the changes seen in OA joints are directly associated with the level or intensity of pain experienced. In clinical practice, there has often been a mismatch between pain severity and the histological changes observed in microscopes.
What Are the Age-Related Orthopedic Problems?
Age-related degeneration contributes much to health issues, deaths, and healthcare costs across the globe. Conditions like osteoarthritis (OA), osteoporosis (OP), and frailty (weak state), which worsen with age, affect people's physical, mental, and emotional well-being. Globally, statistics state that there is an osteoporotic fracture every three seconds, with over 158 million people at high risk of fractures due to low bone mass. Senescent cells will release inflammatory molecules that contribute to aging, and their presence increases to a remarkable number in tissues related to bone health as individuals age.
Fractures caused by osteoporosis and functional limitations in elderly individuals form a remarkable healthcare burden. Latest treatment approaches are immediately needed, specifically the ones that can alter the progression of age-related bone loss rather than just treating the symptoms. Cellular senescence is thought to play a significant role in age-related problems affecting musculoskeletal tissues like cartilage and bone. In osteoporosis, cellular senescence is associated with increased inflammation, lower bone density, reduced cell activity in bone, less cartilage protection, and more signs of cellular aging in bone and joint tissues.
What Are Senolytics?
Senolytics are a group of drugs specifically designed to remove senescent cells. The cellular senescence process involves proliferative arrest (cells stopping their growth permanently), apoptotic resistance (resistance to cell death), and releasing harmful molecules called senescence-associated secretory phenotypes (SASP). These molecules can affect nearby cells and tissues, leading to structural and functional issues. The first senolytic drugs, including Quercetin, Fisetin, Dasatinib, and Navitoclax, were discovered through a targeted approach.
Senescent cells accumulate in the body as one ages and are also seen in areas where chronic diseases develop. It also develops in conditions responsible for a large portion of health concerns and deaths. This allows these cells to survive and continue creating damage, even while neighboring cells are eliminated. Eliminating senescent cells with senolytic drugs will possibly have broad systemic benefits by reducing inflammation initiated by senescent cells. Additionally, intermittent dosing may be enough for therapeutic efficacy, reducing side effects. Since senescent cells do not divide, drug resistance is less concerning compared to other treatments.
Can Senolytics Help Age-Related Orthopedic Problems?
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Aging heightens the risk of osteoarthritis, which is a joint disease causing cartilage damage, reduced function, and pain.
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Current treatment protocols aim to reduce the breakdown or stimulation of bone formation, but they have certain limitations and side effects.
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Senolyitcs now offers a novel approach that targets and eliminates senescent cells specifically, potentially preventing age-related bone issues.
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Based on studies conducted in mice, senolytics have helped clear senescent cells (old cells) and improve joint function, but this effect was limited in older mice.
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Scientists have presumed that using these drugs systemically can be a promising treatment for age-related osteoarthritis pain.
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Research conducted in human and mouse trials has shown that due to aging, there can be joint degeneration, out of which there is an increase in the senescent cells (SnCs).
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Eliminating these senescent cells by using drugs called senolytics has been proven to improve joint health in young animals with joint injuries.
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There has also been a significant reduction in pain and inflammation, promoting cartilage growth.
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Researchers are still working on whether removing senescent cells has a positive effect on spontaneous OA, specifically in reducing joint pain.
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Drugs like Quercetin, Dasatinib, and Fisetin have been found to clear senescent cells effectively without harming healthy cells.
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Combining these drugs can address the effects of senescent cell activity.
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Although the effects of Fisetin on bone health have not yet been studied extensively, it has shown benefits in extending health and lifespan in mice.
What Is the Future of Senolytics in Age-Related Orthopedic Problems?
Recent research suggests that senolytic agents can lessen age-related problems in the joints and bones in a model of accelerated aging. Cellular senescence decides the lifespan and quality of health in an individual. By focussing on these fundamental aging processes, studies have suggested that senolytic drugs can provide a safe alternative in geriatric medicine, potentially preventing many age-related conditions such as cartilage and bone problems.
Moreover, current treatment approaches for osteoporosis usually have side effects from prolonged use and do not address the root causes of the disease. Some chemotherapeutic drugs have been proven to be safe, and natural compounds like Quercetin and Fisetin, available as OTC (over-the-counter) supplements, have shown effectiveness in reducing age-related musculoskeletal issues with minimal side effects, as suggested by few studies.
Conclusion
Aging affects the skeletal system and causes orthopedic problems. The senescent cells and the secretions they produce have a vital role in many clinical disorders. Still, studies are ongoing on the senescent cells' exact role in orthopedic problems during aging and the neurotherapeutic approach for reversing or slowing the aging process. This strategy involves effectively removing senescent cells to alleviate aging symptoms in related diseases. However, it also introduces new challenges, such as the requirement for long-term use and potential side effects. Therefore, it is crucial to better understand how senescent cells cause orthopedic diseases and develop new anti-aging strategies or minimize the side effects of current treatments.
