Procyanidin C1 is a natural agent with senolytic activity against aging and age-related diseases
PCC1 is effective against a wide variety of senescent cell types and has low toxicity:
Cellular senescence per se is a highly heterogeneous process depending on different cell origins and environmental stimuli 55. One of the key features of PCC1 is its ability to efficiently clear senescent cells in a wide spectrum of cell types and stressors, including replication, oncogene, irradiation and chemotherapy. In this study, we compared PCC1 with other reported senolytics was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. bioRxiv preprint doi: https://doi.org/10.1...1.04.14.439765; this version posted April 14, 2021. The copyright holder for this preprint (which23 on human stromal cells, fibroblasts, HUVECs and MSCs, several major cell types in the tissue microenvironment. As reported, ABT263 eliminates senescent HEFs and HUVECs, but shows little effect on human preadipocytes, 12, 18. Combined use of dasatinib and quercetin (‘D + Q’) can deplete all three types of senescent cells in a dose-dependent manner, but is toxic against proliferating cells 11, 56, 57. Fisetin, another natural flavonoid reported as a senolytic agent, displays modest effect on senescent HEFs and preadipocytes only at high concentrations 20, 58. In contrast, PCC1 holds potential to overcome these limitations, including cell-type dependency, high toxicity on non-senescent cells, and low efficiency on senescent cells. Thus, PCC1 has a superior senolytic activity with excellent specificity and efficiency on a wider range of cell types, and covers several major types of senescence inducers.
PCC1 increses life span and healthspan in old mice:
Further, to establish the potential of senescent cell elimination in extending the remaining lifespan of WT mice, we performed intermittent treatment with PCC1 beginning at very old age (Fig. 7k). Notably, mice receiving bi-weekly administration of PCC1 starting at 24-27 months of age (equivalent to age 75-90 years in humans) had 64.2% higher median post-treatment lifespan (or 9.4% higher overall lifespan) and lower mortality hazard (65.0%, P < 0.0001), was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. bioRxiv preprint doi: https://doi.org/10.1...1.04.14.439765; this version posted April 14, 2021. The copyright holder for this preprint (which20 compared to the vehicle group (Fig. 7l,m). These data indicate that PCC1 can significantly decrease the risk of age-associated mortality in old mice.
We next asked whether the reduced death rate in aged animals comes at the cost of an increased late-life morbidity, we measured physical function in experimental mice treated with PCC1 or vehicle monthly until death. Despite the longer remaining lifespan in PCC1-treated mice, physical function in the last 2 months of life was not significantly lower compared to vehicle-treated mice (Fig. 7n).
PCC1 is available from laboratories, but it seems to be quite expensive. Perhaps it possible to absorb enough through GSE and cocoa.