Tier 4 — mechanistic

Targeting Senescence with Apigenin Improves Chemotherapeutic Efficacy and Ameliorates Age-Related Conditions in Mice

Hongwei Zhang, Qixia Xu, Zhirui Jiang, Rong Sun, Qun Wang, Sanhong Liu, Xin Luan, Judith Campisi, James L. Kirkland, Weidong Zhang, Yu Sun
Advanced Science 2025 12(20):e2412950

Bibliography

PubMed
PMID 40265973
PubMed Central
PMC12120719
DOI
10.1002/advs.202412950
Funding
Supported by multiple Chinese public grants, NIH R37 AG13925, Hevolution Foundation support, philanthropic funds, and an Anti-Aging Collaborative Program of SIBS and BY-HEALTH, among other listed sources.
Competing interests
The authors declared no conflict of interest.

Study snapshot

DesignNatural-product screen followed by mechanistic human-cell experiments, cancer-stroma models and mouse preclinical aging/chemotherapy experiments
ModelHuman senescent stromal and fibroblast cell lines; prostate-cancer models; mouse xenograft and whole-body-irradiation premature-aging models
SampleAnimal studies generally used at least 8 mice per group; PC3-only xenograft assays used 3 mice per group.
InterventionApigenin across cell and mouse experiments, including biweekly intraperitoneal treatment in selected in vivo protocols.
DurationVaried by experiment; included acute mechanistic assays and multi-week mouse intervention protocols.
EndpointsSASP factor expression; Senescent-cell viability; PRDX6 and HSPA8 signaling; ATM/p38MAPK interactions; Tumor growth and chemoresistance; Physical frailty; Muscle strength; Cognitive/behavioral outcomes

What the study showed, in plain terms

This 2025 study is one of the most important apigenin papers for geroscience. It found that apigenin behaves primarily as a senomorphic in the tested systems: it dampened the inflammatory secretory program of senescent cells rather than simply killing those cells. The study linked this effect to PRDX6/HSPA8 and ATM-p38MAPK signaling, improved chemotherapy response in preclinical cancer models and reduced several frailty-like features in prematurely aged mice.

Key findings

Apigenin suppressed a broad subset of SASP factors across several senescence models. Mechanistic work identified PRDX6 iPLA2 activity and HSPA8-linked ATM/p38MAPK signaling as key nodes. In mice, apigenin reduced SASP signaling in tumor models, improved chemotherapy-related tumor control and ameliorated physical and cognitive deficits in a premature-aging model.

What this study can and cannot tell us

This is preclinical evidence. The aging model used whole-body irradiation to induce a premature-aging-like state and does not reproduce normal human aging. Intraperitoneal administration and experimental doses cannot be equated with oral supplement exposure, and no human clinical longevity endpoint was tested.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology