The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases

Mar 6, 2026Nature communications

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

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Dihydromyricetin, a natural flavonoid, shows potential as a senotherapeutic agent in various age-related disorders.

Dihydromyricetin protects senescent fibroblasts from additional DNA damage.
It reduces the senescence-associated secretory phenotype, functioning as a senomorphic agent.
In prematurely aged mice, dihydromyricetin administration mitigates tissue aging and physiological decline.
The compound improves chemotherapy outcomes in anticancer treatments.
Dihydromyricetin induces apoptosis in senescent microglial cells by impairing their mitochondrial function.
In mice with Alzheimer's disease, it eliminates senescent microglial cells from amyloid β-protein plaques and alleviates neurodegenerative symptoms.

AI 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.