The combination of the chemotherapeutic drug dasatinib and the widely used plant extract supplement quercetin was the first senolytic therapy to clear senescent cells from aged tissues to be assessed in mice and humans. The degree of clearance of senescent cells and degree of reversal of aspects of aging and age-related disease produced by dasatinib and quercetin treatment remain comparable to the best of the later panoply of senolytic therapies for which published data exists. Dasatinib produces unpleasant side-effects when used as a chemotherapeutic with dosing regiments sustained over months, but short term use as a senolytic treatment over the course of a few days appears to have a favorable side-effect profile, judging from the published clinical trials. The dose makes the poison.
The challenge with dasatinib and quercetin (as well as the alternative of fisetin) is that there is no financial incentive for any organization to run extensive clinical trials to conclusively prove to the medical community that that these treatments are meaningfully beneficial in older people. These are very cheap compounds, with no patent protection. Without patent protection, and the consequent government-enforced monopoly in the market, it is impossible to obtain the sort of elevated program valuation and elevated drug prices needed to make a profit after spending hundreds of millions of dollars on clinical trials. The fault here is the regulatory burden that causes clinical trials to be so expensive. There must be a better path forward; as things stand, even very good low-cost drugs can languish in this state of being understood to be potentially great, prescribed off-label by some physicians, but never reaching any sort of widespread use or validation sufficiently comprehensive to convince the world at large.
That the dasatinib and quercetin senolytic therapy is understood by the research community to be potentially great is why one sees any clinical trials at all for this approach to the problem of senescent cell accumulation in later life. Various research institutions agitate behind the scenes to obtain philanthropic and other funding to try to move the needle. There is never enough of this funding, and the clinical trials are always too small, but one might hope that at some point a critical mass is reached and a more earnest clinical program is funded by one of the world's larger alternative sources of funding.
Cellular senescence is one of the hallmarks of ageing that theoretically contributes to the development of age-related diseases. Senolytic agents such as Dasatinib and Quercetin promote the elimination of senescent cells and may provide a viable strategy for the prevention or treatment of diseases of ageing. Studies have demonstrated that co-administration of Dasatinib and Quercetin improved aspects of both physical and cognitive function in mice. However, to our knowledge, the safety, feasibility, and preliminary efficacy of Dasatinib and Quercetin to improve function in humans with mild cognitive impairment (MCI) and slow gait speed is unknown.
This single-arm study evaluates the feasibility, safety, and preliminary effects of two senolytic agents, Dasatinib and Quercetin (DQ), in older adults at risk of Alzheimer's disease. Participants took 100 mg of Dasatinib and 1250 mg of Quercetin for two days every two weeks over 12 weeks. Recruitment rate, adverse events, absolute changes in functional outcomes, and percent changes in biomarkers were calculated. Spearman correlations between functional and biomarker outcomes were performed.
Approximately 10% of telephone-screened individuals completed the intervention (n = 12). There were no serious adverse events related to the intervention. Mean Montreal Cognitive Assessment (MoCA) scores non-significantly increased following DQ by 1.0 point, but increased significantly by 2.0 points in those with lowest baseline MoCA scores. Mean percent change in tumour necrosis factor-alpha (TNF-α), a key product of the senescence-associated secretory phenotype (SASP), non-significantly decreased following DQ by -3.0%. Changes in TNF-α were significantly and inversely correlated with changes in MoCA scores, such that reductions in TNF-α were correlated with increases in MoCA scores.
This study suggests that intermittent DQ treatment is feasible and safe; data hint at potential functional benefits in older adults at risk of Alzheimer's disease. The observed reduction in TNF-α and its correlation with increases in MoCA scores suggests that DQ may improve cognition by modulating the SASP. However, there was not an appropriate control group. Data are preliminary and must be interpreted cautiously.
View the full article at FightAging
