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Updated: Jul 17, 2026
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on
Edwin Lee1, Natàlia Carreras-Gallo2, Leilani Lopez2
1Institute For Hormonal Balance, Orlando, FL 32819, USA.
Abstract:
Senolytics, small molecules targeting cellular senescence, have emerged as potential therapeutics to enhance health span. However, their impact on epigenetic age remains unstudied. This study aimed to assess the effects of Dasatinib and Quercetin (DQ) senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets. In a Phase I pilot study, 19 participants received DQ for 6 months, with DNAm measured at baseline, 3 months, and 6 months. Significant increases in epigenetic age acceleration were observed in first-generation epigenetic clocks and mitotic clocks at 3 and 6 months, along with a notable decrease in telomere length. However, no significant differences were observed in second and third-generation clocks. Building upon these findings, a subsequent investigation evaluated the combination of DQ with Fisetin (DQF), a well-known antioxidant and antiaging senolytic molecule. After one year, 19 participants (including 10 from the initial study) received DQF for 6 months, with DNAm assessed at baseline and 6 months. Remarkably, the addition of Fisetin to the treatment resulted in non-significant increases in epigenetic age acceleration, suggesting a potential mitigating effect of Fisetin on the impact of DQ on epigenetic aging. Furthermore, our analyses unveiled notable differences in immune cell proportions between the DQ and DQF treatment groups, providing a biological basis for the divergent patterns observed in the evolution of epigenetic clocks. These findings warrant further research to validate and comprehensively understand the implications of these combined interventions.
Insights
Senolytic treatment with Dasatinib and Quercetin (DQ) accelerated epigenetic aging. Adding Fisetin (DQF) mitigated this effect, showing potential for healthier aging interventions.
Area of Science:
- Gerontology and Aging Research
- Cellular Senescence and Epigenetics
- Immunology and Aging
Background:
- Cellular senescence is a hallmark of aging, targeted by senolytics to enhance healthspan.
- The impact of senolytics on epigenetic age, a molecular measure of aging, is largely unstudied.
- Dasatinib and Quercetin (DQ) are senolytic drugs with potential anti-aging applications.
Purpose of the Study:
- To investigate the effects of DQ senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets.
- To evaluate the impact of combining DQ with Fisetin (DQF) on epigenetic aging.
- To explore the relationship between immune cell changes and epigenetic age alterations.
Main Methods:
- A Phase I pilot study involving 19 participants treated with DQ for 6 months, with DNAm analysis at multiple time points.
- A subsequent investigation with 19 participants (10 from the initial study) treated with DQF for 6 months, with DNAm assessed at baseline and 6 months.
- Analysis of DNA methylation data using first, second, and third-generation epigenetic clocks and mitotic clocks.
Main Results:
- DQ treatment led to significant epigenetic age acceleration and telomere shortening in first-generation and mitotic clocks.
- No significant changes were observed in second and third-generation epigenetic clocks with DQ treatment.
- The addition of Fisetin to DQ (DQF) resulted in non-significant increases in epigenetic age acceleration, suggesting a mitigating effect.
- Distinct differences in immune cell proportions were observed between DQ and DQF treatment groups, correlating with epigenetic clock patterns.
Conclusions:
- DQ senolytic treatment may accelerate epigenetic aging, while Fisetin addition could mitigate this effect.
- Immune cell subset alterations may underlie the divergent effects of DQ and DQF on epigenetic aging.
- Further research is needed to validate these findings and understand the clinical implications of combined senolytic interventions for aging.
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