“The Flavonoid Procyanidin C1 Has Senotherapeutic Activity and Increases Lifespan in Mice”, 2021-12-06 (; similar):
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).
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. 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.
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. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival.
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.
…To establish the potential of senescent cell elimination to extend the remaining lifespan of WT mice, we performed PCC1 treatment beginning at a very old age (Figure 8k). Mice receiving PCC1 administration (once every 2 weeks or biweekly) starting at 24–27 months of age (roughly equivalent to an age of 75–90 years in humans) had a 64.2% longer median post-treatment lifespan (or 9.4% longer overall lifespan) and lower mortality hazard (65.0%, p < 0.0001) than the vehicle-treated group (Figure 8l, Figure 8m). These data indicate that PCC1 can substantially decrease the risk of age-associated mortality in old mice.