Nature communicationsMar 6, 2026

The natural compound dihydromyricetin targets aging cells through PRDX2 and may reduce age-related diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Dihydromyricetin showed senotherapeutic effects in senescent cells and improved aging-, chemotherapy-, and Alzheimer's-related outcomes in mouse models.

Evidence

Preclinical cell-screening, proteomics, and mouse-model experiments tested dihydromyricetin in senescent fibroblasts, senescent microglia, prematurely aged mice, anticancer regimens, and Alzheimer's-model mice.

Caveat

The evidence is preclinical, with mechanisms and disease benefits shown in cells and mice rather than human trials.

Simplified

Aging is a primary risk factor for chronic diseases, with cellular senescence as an effective target to delay, prevent or alleviate age-related disorders. Here we report in vitro screening outputs from a natural medicinal agent library, wherein dihydromyricetin, a natural flavonoid, showed senotherapeutic potential. Dihydromyricetin protects senescent fibroblasts against further DNA damage and attenuates the senescence-associated secretory phenotype, acting as a senomorphic agent. Proteomics suggests that dihydromyricetin promotes nuclear translocation of peroxiredoxin 2 (PRDX2) to facilitate DNA repair in senescent cells. In prematurely aged mice, dihydromyricetin administration mitigates tissue aging and age-related physiological decline. In anticancer regimens, dihydromyricetin improves outcomes of chemotherapy. However, dihydromyricetin demonstrates senolytic activity against senescent microglial cells, whose basal PRDX2 expression remains low, by impairing mitochondrial function to promote apoptosis. In mice developing Alzheimer's disease, dihydromyricetin eliminates senescent microglial cells from amyloid β-protein plaques and alleviates neurodegenerative symptoms. Together, our study proposes dihydromyricetin as a natural senotherapeutic agent for mitigating age-related morbidities, including but not limited to cancers and Alzheimer's disease.