Arthritis, marked by joint inflammation, significantly impacts the lives of millions globally, manifesting as pain, stiffness, and diminished mobility. Beyond traditional therapies, senolytics—emerging healthy ageing supplements—offer a novel approach by targeting senescent cells associated with the progression of arthritis. This detailed guide delves into the roles of senolytics, specifically fisetin and quercetin, in alleviating arthritis symptoms, shedding light on their potential benefits in managing this challenging condition.
What is Arthritis?
"Arthritis" directly translates to joint inflammation. While joint inflammation typically serves as a symptom rather than a precise diagnosis, "arthritis" commonly encompasses any disorder impacting joint health.
The most prevalent types include osteoarthritis, resulting from wear and tear on the joints over time; rheumatoid arthritis, an autoimmune disorder where the immune system mistakenly attacks the joints; and psoriatic arthritis and its symptoms are linked with psoriasis, a skin condition marked by red patches with silvery scales. While most people develop psoriasis before psoriatic arthritis, joint issues can arise before or alongside skin symptoms. Gout is a type of arthritis characterised by the formation of sharp uric acid crystals in joints.
What is the Role of Senescent Cells in Arthritis?
Senescent cells accumulate with age and are implicated in cancer, cardiovascular disease, neurodegenerative disorders, and more. Senescent cells, also known as zombie cells, have a significant impact on arthritis, including both osteoarthritis (OA) and rheumatoid arthritis (RA). In the context of arthritis, senescent cells accumulate within the joints, damaging the tissue and cartilage, and influencing the progression of the disease. Senescent cells undergo various biochemical and morphological changes, leading to their identification by distinctive markers such as senescence-associated β-galactosidase (SA-β-gal) activity, increased expression of genes, and secretion of pro-inflammatory molecules collectively known as the senescence-associated secretory phenotype (SASP).
Senescent Cells in Osteoarthritis
In OA, these ageing cells called senescent chondrocytes, cartilage and bone cells, build up in the cartilage of joints and make the disease worse. They are a problem because they break down cartilage and make the tissue around the joint inflamed. This inflammation keeps OA going and even causes other issues like swelling in the lining of the joint and changes in the bone underneath the cartilage. Also, these ageing cells can send out signals that stop nearby healthy chondrocytes from doing their job. Scientists have found some specific pathways inside these ageing cells that could be targeted for new treatments. (Xie et al., 2021).
Senescent Cells in Rheumatoid Arthritis
In rheumatoid arthritis (RA), senescent cells, particularly aged fibroblast-like synoviocytes (FLS) in the joint lining, significantly contribute to the disease's severity. These senescent cells fail to undergo programmed cell death and instead produce various inflammatory cytokines that cause inflammation. They also alter immune system functions in RA, leading to the attack on the body's tissues and the production of damaging antibodies. Furthermore, these aged cells facilitate the formation of clusters within the joint lining of harmful immune cells, increasing joint damage. Targeting these senescent cells presents a promising strategy for RA management, aiming to reduce inflammation, preserve joint integrity, and alleviate symptoms. (Weyand et al., 2003).
What Are Senolytics and How Do They Eliminate Senescent Cells?
Senolytics are drugs that selectively remove senescent cells, which are harmful cells that avoid self-destruction and protect themselves against their inflammatory secretion, known as the senescence-associated secretory phenotype (SASP). By blocking the protective mechanisms of these senescent cells, senolytics trigger their self-destruction, specifically targeting those with an SASP. Direct senolytics are classified into two groups: Stressors and protection repressors.
Increase the Stressors
Senolytics eliminate senescent cells by exploiting the cells' vulnerabilities to certain stressors. Senescent cells, despite their resistance to apoptosis through anti-apoptotic pathways, often have a higher baseline level of stress due to factors like DNA damage, mitochondrial dysfunction, and the pro-inflammatory state associated with the SASP. Certain senolytics target and amplify these stressors or inhibit the protective pathways that senescent cells rely on to survive under such stress. This increased stress overwhelms the senescent cells, leading to their apoptosis while sparing healthy cells, which have more robust stress response mechanisms.(Rad & Grillari, 2024)
Induce Apoptosis by Reducing Protection
Senolytics induce apoptosis, or programmed cell death, in senescent cells by temporarily disrupting the cell's protective mechanisms, known as senescence-associated anti-apoptotic pathways (SCAPs). These pathways help senescent cells resist apoptosis, despite their harmful effects on neighboring cells through the senescence-associated secretory phenotype (SASP). By targeting and inhibiting these anti-apoptotic pathways, senolytics effectively remove these resistant senescent cells, allowing for the elimination of cells contributing to tissue damage and ageing-related diseases.
Senolytics Used to Potentially Relieve Arthritis
Senolytics used in mitigating arthritis, such as fisetin and quercetin, target and remove senescent cells linked to joint inflammation and degeneration, showing promise in alleviating symptoms and potentially slowing disease progression.
Fisetin
Fisetin, a natural flavonoid found in many fruits and vegetables, has shown promise in the treatment of arthritis due to its potent senolytic properties. It eliminates senescent cells by inducing apoptosis, thereby reducing chronic inflammation. Research indicates that fisetin can significantly impact bone and cartilage health, which is crucial in managing arthritis. It has been demonstrated to delay the progression of musculoskeletal conditions like osteoporosis and osteoarthritis by promoting bone formation and protecting against inflammation-induced bone loss. Fisetin's effectiveness in arthritis treatment is attributed to its anti-inflammatory activities. These properties not only help in reducing joint inflammation but also in preventing tissue breakdown around the joints, offering a natural and effective approach to improving joint health and alleviating arthritis symptoms (W. Zheng et al., 2017b).
Quercetin
Quercetin, a bioactive flavonoid present in many fruits and vegetables, offers promise for treating arthritis through its anti-inflammatory and joint-protective properties. Its ability to eliminate senescent cells, often implicated in arthritis-related inflammation and tissue damage, potentially enhances joint health and functionality. This senolytic activity, coupled with its anti-inflammatory benefits, makes quercetin an agent in arthritis management. Research has highlighted its effectiveness in mitigating inflammation and joint deterioration in conditions like rheumatoid arthritis and osteoarthritis. Quercetin targets and inhibits neutrophils' inflammatory actions, crucial in the development and progression of rheumatoid arthritis.
Conclusion
Compounds such as fisetin and quercetin are leading the way in the exploration of senolytics for arthritis treatment, focusing on the elimination of senescent cells that play a key role in joint inflammation and damage. Beyond their direct effects on senescent cells, these compounds are also recognised for their antioxidant and anti-inflammatory capabilities, which contribute to symptom relief and potentially may slow the advancement of arthritis. This approach adds a novel dimension to arthritis therapy, emphasising the importance of cellular health in managing the disease and opening new doors for research and development in the field.
FAQs
1) What is Arthritis?
Arthritis refers to a group of disorders characterised by inflammation in the joints, such as knees or elbows. It encompasses over 100 different types, with symptoms including joint pain, stiffness, swelling, and tenderness. Common types include osteoarthritis from joint wear and tear, rheumatoid arthritis from immune system malfunction, and gout from uric acid crystals. Arthritis can affect any age group, impairing joint function and overall quality of life.
2) What is the main cause of arthritis?
Arthritis comes in different types and has different causes. Osteoarthritis usually happens when joints wear out over time, causing the cartilage to break down. Rheumatoid arthritis occurs because the immune system attacks the joints, leading to inflammation. Other factors like high uric acid levels, viral infections, and unknown reasons can also lead to arthritis. Genetics, problems with the immune system, and getting older can all make someone more likely to develop arthritis.
3) What are the symptoms of arthritis?
Symptoms of arthritis typically include joint pain, stiffness, swelling, and reduced range of motion. Affected joints may appear warm and tender to the touch, with redness or skin discolouration possible. Symptoms can vary in intensity and duration, depending on the type of arthritis and individual factors. In addition to joint symptoms, some forms of arthritis may cause fatigue, fever, and weight loss, impacting overall well-being.
4) What is the fastest way to treat arthritis?
The fastest way to treat arthritis involves a multifaceted approach. Immediate relief can be achieved through over-the-counter or prescription medications to alleviate pain and inflammation. Physical therapy can improve joint mobility and strengthen surrounding muscles. Additionally, lifestyle modifications such as maintaining a healthy weight, exercising regularly, and applying hot or cold therapy can provide rapid relief. In severe cases, joint injections or surgery may be necessary for prompt management of symptoms or restoration of joint function.
5) Can arthritis be cured permanently?
Currently, arthritis cannot be permanently cured. However, various treatments and therapies aim to manage symptoms, slow disease progression, and improve the quality of life for individuals affected by arthritis. These include medications, physical therapy, lifestyle modifications, and in severe cases, surgery. While these interventions can effectively control symptoms and delay joint damage, arthritis remains a chronic condition without a definitive cure, emphasizing the importance of ongoing management and support.
6) Can arthritis be dangerous?
Yes, arthritis can be dangerous, especially if left untreated or poorly managed. Severe forms of arthritis, such as rheumatoid arthritis, can lead to joint deformities, disability, and systemic complications affecting organs like the heart and lungs. Additionally, chronic inflammation associated with arthritis increases the risk of cardiovascular disease and other comorbidities. Proper diagnosis, treatment, and management are crucial to mitigate the potential dangers posed by arthritis.
7) What is the best supplement for arthritis?
The best supplements for mitigating arthritis symptoms include Decode Age's Ca-AKG and senolytics such as Quercetin and Fisetin. These supplements aid in eliminating senescent cells from the body, thereby reducing inflammation and potentially slowing down the progression of arthritis. Incorporating these supplements into a comprehensive arthritis management plan offers relief and improves joint health.
8) What are the top three joint supplements?
The top three joint supplements include glucosamine, chondroitin, and methylsulfonylmethane (MSM). Additionally, senolytics like fisetin and quercetin are gaining attention for their potential benefits in supporting joint health. These compounds target senescent cells, which contribute to inflammation and tissue degeneration in joints, potentially aiding in joint function and mobility. Always consult with a healthcare professional before starting any supplement regimen.
9) Which vitamin is best for arthritis?
Vitamin D is often considered beneficial for arthritis due to its role in bone health and immune function. Adequate vitamin D levels may help reduce inflammation and alleviate joint pain associated with arthritis. Research suggests that vitamin D deficiency is prevalent in arthritis patients, and supplementation may improve symptoms. However, it's essential to consult a healthcare professional for personalized advice on vitamin D supplementation and arthritis management.
10) Which is the best fisetin supplement in India?
Decode Age Fisetin stands out as one of the most potent senolytics in India due to its exceptional quality, efficacy, and safety measures. Renowned for its purity and potency, it enjoys widespread trust among consumers. Supported by robust scientific research, it's recognized for its ability to deliver tangible health benefits, making it a preferred choice for those seeking reliable supplements for their well-being.
References
1.Xie, J., Wang, Y., Lu, L., Liu, L., Yu, X., & Pei, F. (2021). Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications. Ageing research reviews, 70, 101413.
https://doi.org/10.1016/j.arr.2021.101413
2.Weyand, C. M., Fulbright, J. W., & Goronzy, J. J. (2003). Immunosenescence, autoimmunity, and rheumatoid arthritis. Experimental gerontology, 38(8), 833-841.
https://doi.org/10.1016/S0531-5565(03)00090-1
3.Zheng, W., Feng, Z., You, S., Zhang, H., Tao, Z., Wang, Q., ... & Wu, Y. (2017). Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. International immunopharmacology, 45, 135-147.
http://dx.doi.org/10.1016/j.intimp.2017.02.009
- Rad, A. N., & Grillari, J. (2024). Current senolytics: Mode of action, efficacy and limitations, and their future. Mechanisms of Ageing and Development, 217, 111888. https://doi.org/10.1016/j.mad.2023.111888
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