Cellular senescence is a fundamental process associated with aging. Recent evidence suggests that the accumulation of senescent cells, which can release a variety of toxic, inflammatory by-products, is one of the drivers of deficits in both cognition and mobility. Senolytic drugs like dasatinib and quercetin target and help eliminate senescent cells, potentially slowing aging and reducing the risk of age-related diseases. An earler study of 5 patients with early Alzheimer’s disease treated intermittently with Dasatinib and Quercetin for 12 weeks, showed a favourable safety profile, penetrance of Dasatinib into the cerebral spinal fluid (CSF), increased levels of CSF interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP), non-significant decreases in senescence-related cytokines and chemokines and non-significant increases in Aβ42 levels.
That small study supported the safety, tolerability and feasibility of Dasatinib and Quercetin treatment in patients with Alzheimer’s disease. A new pilot study known as STAMINA (Senolytics To Alleviate Mobility Issues and Neurological Impairments in Aging) focused on the effects of two senolytic molecules, Dasatinib and Quercetin (DAQU protocol), which remove old (senescent) cells from the body, suggests that intermittent treatment may hold promise for improving cognitive function in older adults at risk of Alzheimer’s disease. Published in the eBioMedicine journal, the research explored the effects of DAQU on cognition and mobility in individuals with mild cognitive impairment (MCI) and slow gait, which are conditions linked to increased risk of Alzheimer’s disease.
The results showed an improvement in cognitive scores, particularly among participants with the lowest baseline cognitive function and a reduction in a key inflammatory chemical in the blood associated with cellular aging. Over 12 weeks, 12 participants took a combination of Dasatinib (100mg) and Quercetin (1250mg) for two days every two weeks. Researchers observed a statistically significant increase of 2 points in the Montreal Cognitive Assessment (MoCA) scores in participants with the lowest baseline scores. That was hinting at potential cognitive benefits. Additionally, reductions in the inflammatory cytokine tumor necrosis factor alpha (TNF-α) correlated with cognitive improvements, suggesting that senolytics might enhance cognitive function by reducing brain inflammation.
Unfortunately, study design was not adequately powered to confidently detect statistically significant changes in the functional and biomarker outcomes. Rather, the goal of the current trial was to collect data on the variation of these measures, which would be used to inform a power analysis for a larger trial. Beside, in all participants, MoCA scores increased by only 1 point, which may not be clinically meaningful. Therefore, the team stated that to unequivocally determine if DAQU improves cognition, future trials will need a larger sample size and the inclusion of a placebo control group. The strong backing of the trial is the notion that polyphenol supplementation or the consumption of polyphenol- or quercetin-enriched foods are deemed to prevent mild cognitive impairment, as proved in earler investigations.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Millar CL et al. eBiomed. 113; 2025:105612; in press.
Oei S, Millar CL et al. Amer J Clin Nutr. 2023; 118(1):27-33.
Millar CL et al. J Gerontol A Biol Sci Med Sci. 2023; 78(2):250.
Chaib, S et al. Nature Med. 2022; 28:1556-1568.
