Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions.

TitleExploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions.
Publication TypeJournal Article
Year of Publication2024
AuthorsLee E, Carreras-Gallo N, Lopez L, Turner L, Lin A, Mendez TL, Went H, Tomusiak A, Verdin E, Corley M, Ndhlovu L, Smith R, Dwaraka VB
JournalAging (Albany NY)
Volume16
Issue4
Pagination3088-3106
Date Published2024 Feb 22
ISSN1945-4589
KeywordsAging, Dasatinib, DNA Methylation, Epigenesis, Genetic, Flavonols, Humans, Longitudinal Studies, Pilot Projects, Quercetin, Senotherapeutics
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.

DOI10.18632/aging.205581
Alternate JournalAging (Albany NY)
PubMed ID38393697
PubMed Central IDPMC10929829