The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

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 PCC1-mediated senolysis prevents physical dysfunction and alleviates pathological symptoms.

This phenomenal research identified a naturally occurring senotherapeutic ingredient in grape seed extract.

Upon ageing, the accumulation of senescent cells, which develop senescence-associated secretory phenotype (SASP), partially drives functional decline in organs, and elevates the risk of age-related chronic pathologies. In this study the researchers showed that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells.

- PCC1 appeared to inhibit SASP formation at low concentrations, but at higher concentration it seemed to selectively kill senescent cells, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction.

- In rodent models, PCC1 depleted senescent cells in a treatment-damaged tumour microenvironment and enhanced therapeutic efficacy when co-administered with chemotherapy.

- PCC1, administered intermittently to either irradiated, senescent cell-implanted or naturally aged old mice alleviated physical dysfunction and prolongs survival.

In summary, PCC1 is a natural senotherapeutic agent with in vivo activity and has high potential in therapeutics development to delay, alleviate or prevent age-related pathologies.

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Authors: Xu, Q., Fu, Q., Li, Z. et al.

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