Fisetin compound restores immune cell function and physical performance in aging, study finds
A new preprint study reports that the natural compound fisetin can reverse age-related decline in macrophage immune function by restoring levels of the MYC transcription factor in human cells, flies, and mice. Macrophages — key innate immune cells — lose their ability to engulf pathogens and migrate effectively with age, a process the researchers link to falling MYC levels. The findings suggest a potential dietary supplement-based strategy to combat age-related immune decline and physical frailty, though the research has not yet undergone peer review.
Researchers publishing on bioRxiv report that fisetin, a naturally occurring flavonoid already marketed as a geroprotective supplement, can restore age-impaired macrophage functions by reversing the decline in MYC transcription factor expression. The study used three model systems: human primary macrophages from older donors, Drosophila (fruit flies), and older mice. In human macrophages, fisetin treatment improved phagocytosis of pathogens and cell migration to levels comparable to those seen in younger individuals. In Drosophila, macrophage-specific overexpression of Myc improved physical performance without extending lifespan. In older mice, fisetin feeding reduced frailty and improved motor activity while also restoring macrophage Myc expression and function in vitro. Mechanistically, the team found fisetin acts through the MYC pathway, restoring expression of MYC target genes that are dysregulated with age. The authors propose MYC restoration in macrophages as a rational therapeutic target for reversing age-related immune and physical decline.
What's missing
As a preprint, this study has not yet been peer-reviewed. Key limitations include the in vitro nature of the human macrophage experiments (which may not reflect in vivo complexity), and the lack of data on optimal fisetin dosing, bioavailability, or safety in older humans at doses sufficient to achieve the observed effects. The study does not address whether fisetin's benefits persist long-term or whether MYC upregulation in macrophages carries oncogenic risk with chronic use.
What different sources said
- bioRxivCenter
Fisetin-mediated MYC restoration improves age-associated decline in macrophage function
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