Experimental Use of Quercetin and Dasatinib for Anti-aging: Benefits, Dosages, Cost, Risks and Where to Get the Drugs

Aging is a natural process in several biological species and humans. The mechanism of aging is multifactorial and characterized by multiple degenerative processes. These changes are due to various alterations in molecular pathways. The molecular changes hinder the full functionality of cells and tissues. Because of its multiple physiological variations, aging is the leading etiological factor for several diseases, including cardiovascular, neurological, cancers, diabetes, and other systemic diseases. The prevalence and impact of aging-related diseases are on the increase globally. Dasatinib

Scientists involved in aging studies have aimed to determine the exact causes, how to stop aging, and other therapeutic means that may contribute to slowing down aging. Cellular senescence is known as the main cause of aging and age-related diseases. It is a process that involves the non-reversible proliferative arrest of body cells in response to various stressors. Current therapeutic interventions for aging are targeted at cellular senescence. The development of numerous senolytic drugs has dominated modern aging science studies. These medications carry a potential for specific targeting and removal of senescent cells. This therapy approach aims to restore an organism’s tissue and cellular functions and prevent aging. Among the most widely used senolytic drugs are Dasatinib and Quercetin. These drugs have a wide array of therapeutic uses in aging, and a combination of both is not uncommon in anti-aging studies. Combination therapy of Dasatinib and Quercetin can decrease the number of senescent cells, improve tissue survival, alleviate fibrotic pulmonary diseases, and reduce physical dysfunction, as seen in some human studies.

Although a higher number of research studies focused on mice models, some anti-aging studies focused on the combined effect of these senolytic medications on human subjects. These findings indicate a potential therapeutic promise for use in humans to address aging.

Combining Dasatinib and Quercetin for anti-aging effects

Cellular senescence is the irreversible fate of biological cells. Various research evidence shows that chronological aging can increase the senescent cell burden. The therapeutic management with senolytic drugs in aged mice models shows a reduction in several aging-related phenotypes. Although it has proved scientifically difficult to reverse biological aging in humans, the combination of Dasatinib and Quercetin shows evidence as a safe and effective treatment option to improve the features of aging. Research studies show these drugs’ combination slows down cell proliferation and decreases aging and the risk of age-related diseases.

The replication of these cell types links with functional decline in multiple tissues and body organs. The ability of the senescent cells to be metabolically active makes it easier to acquire tissue-destructive and pro-apoptotic traits, although the cells themselves are resistant to apoptosis.

Senescent cells contain factors that can cause inflammation and cell dysfunction. These cells accumulate as people age. Senolytics are drugs that can specifically target senescent cells by causing a forced death of these cells. These senolytics do not affect non-senescent cells. The potential to delay age-related senescent cell types increase can increase a healthy lifespan and reduce diseases associated with aging.

The first discovered senolytic drugs were Dasatinib and Quercetin. They were discovered with a mechanism-based approach targeting senescent cells instead of the random high-throughput method recommended for drug discovery. The discovery method limits the combination potentials in the application. The impact on molecules or biochemical pathways is unknown due to its lack of target on these pathways.

Although this combination of drugs has not been approved for use in general human populations as an anti-aging treatment, prospective clinical studies have evaluated the effectiveness of a combination supplement on the epigenetic aging rate of study participants. The results predict considerable therapeutic effects of these drug combinations in decelerating aging and prolonging longevity.

Mechanisms of action

Various senolytics, including a combination of Dasatinib and Quercetin, can selectively remove these increasing senescent cells. The mechanism of action for these drugs is by transiently disabling the survival networks that protect senescent cells from apoptosis.

Quercetin. Credit : Swanson

These drugs act independently and have some restrictions. For example, Dasatinib does not target endothelial cells in humans and Quercetin does not effectively target senescent human adipocyte progenitors. To address these limitations, researchers adopted a combination of both medications to extend the range of senescent cells targeted.

Several studies show eliminating up to 30% of senescent cells can sufficiently eliminate age-related dysfunction. Thus, a combination of both novel senolytics functions effectively in this regard. The drug combination is administered intermittently and continuously because of their short half-lives.

The first human trial using both drug combinations showed a significant increase in improving physical functions in subjects with cellular senescence-driven diseases. This application brought to light the potential use of this drug combination in reducing aging.

Senolytics do not need to be continuously present in the circulation because their target is senescent cells, unlike drugs whose mechanism of action is to occupy a receptor, modulate an enzyme, or act on a specific biochemical pathway, at least in mice. Intermittent combined administration effectively avoids potential off-target effects caused by constant receptor occupancy or modulation of an enzyme or biochemical pathway.

Dosage

There is presently no clinical consensus on recommended dosage of senotherapeutics. Various studies on human models used different medications dose relative to their study aims. A research study applied a combination of 100mg of Dasatinib and 500mg of Quercetin to participants over a three days course. They reported a decrease in senescent cell markers. Another study utilized 50 mg of Dasatinib and 500 mg of Quercetin for three consecutive days monthly over six months. They also reported slower cell proliferation rates and reduced rates of aging. More clinical research is required to get population-specific doses of senolytics to improve anti-aging features with reduced side effects.

Cost

Dasatinib and Quercetin stand out because they are already available. A senolytic therapy would be used only once every few years at most; it kills the unwanted cells it can kill, and it would be pointless to repeat it before enough time had passed for new senescent cells to emerge at their slow pace. Quercetin is a popular supplement that usually costs less than a dollar for a single treatment. However, depending on the manufacturers, it can cost as much as $35.

Manufacturers sell Dasatinib for between $20 and $150 for a single dose suitable for senolytic therapy. Sprycel, the FDA-approved packaging of Dasatinib, costs $300-600 for the same amount, assuming a breakdown of the bottle of tablets is done and selling the small amount required. Sprycel can be purchased for less than this price if ordered from outside the United States.

If this pharmaceutical combination works in humans as an anti-aging supplement, it can be afforded by a sizable portion of the world’s population if the prices do not increase. However, both are not the only candidate senolytic drugs that are not much expensive enough to be considered.

Dasatinib and Quercetin can be ordered online from Amazon and shipped to any part of the world. Retail pharmacies market these drugs depending on location.

Risk

The combination of Dasatibin and Quercetin has only been applied in controlled clinical trials. Hence, it is difficult to show its risks and side effects at population levels. In the drug trials, there were no significant risks reported. The combination proved to be effective in eliminating senescent cells in various tissues.

Senolytics have been shown in pre-clinical studies in mice to delay, prevent, or alleviate a variety of age- and senescence-related conditions. These conditions include frailty, cataracts, age-related osteoporosis, age-related muscle loss, radiation-induced damage, cardiac dysfunction, vascular dysfunction and calcification, pulmonary fibrosis, hepatic steatosis, metabolic syndrome, diabetes, and dementia. Overall, senolytic agents and the elimination of senescent cells have been shown in mice to improve physical function and extend health span and lifespan.

The findings of the first-in-human, single-arm, open-label clinical trial of senolytics were published in 2019. Subjects with idiopathic pulmonary fibrosis, a fatal disease caused by cellular senescence, showed significantly improved walking endurance, gait speed, chair rise test performance, and Short Physical Performance Battery scores five days after nine doses of a combination treatment with Dasatinib and Quercetin.

Conclusion

The use of a drug combination with Dasatinib and Quercetin could find use in enhancing healthspan and survival in the aging process. Due to the role of senescent cells in causing age-related degeneration, these widely known senolytics show a possibility of reducing this biological process. The desire to live longer may be a possibility in the future if the pharmaceutical combination of anti-aging drugs is proven for wider population use. Presently it is still in controlled drug trials with no known side effects. A potential application of this combination can also help reduce comorbidities associated with old age. With research evidence of its benefits in improving physiological function and performance, researchers predict a significant advancement in anti-aging science using this therapeutic method.