Several major factors affecting healthspan and lifespan have been identified through studies across a range of species and defined as ageing mechanisms that can be categorized into nine hallmarks 3.
However, the combined effect of these drugs in controlling morbidity and mortality of chronic diseases has been modest, and these diseases tend to occur in synchrony as multimorbidities, with prevalence increasing exponentially after 70 years of age 2. Considerable progress has been made over recent years to develop specific agents to treat individual age-related conditions, such as type 2 diabetes, osteoporosis, skeletal fragility and vascular dysfunction. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical intervention to delay, alleviate or prevent age-related pathologies.Īgeing is one of the biggest risk factor for chronic disorders, including cardiovascular diseases, metabolic disorders, neurodegenerative pathologies and diverse malignancies, which together account for the bulk of morbidity, mortality and health costs globally 1. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. Here we show 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. Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP).