Nature: how does proanthocyanidin C1 in grape seeds prolong life?
- Not long ago, SunYu's research team from the Shanghai Institute of nutrition and health, Chinese Academy of Sciences, successfully discovered a new star in the anti-aging world, procyanidin C1 (PCC1).
- Procyanidin C1 is a natural compound in grape seed extract. Researchers found that procyanidin C1 can efficiently and selectively remove senescent cells produced by various types and inducements without affecting proliferating cells, breaking through the limitations of current anti-aging drugs.
- The remaining healthy life span of aging mice can be extended by 64.2% after receiving procyanidin C1 treatment. The combined treatment of procyanidin C1 and chemotherapy drugs can even improve the anticancer efficacy of chemotherapy drugs. The article was published in the journal Nature metabolism.
- There are a group of "old but not dead zombie cells" - senescent cells in our body. These cells basically stop proliferation, but still retain metabolic activity, secreting senescence associated secretory phenotype (SASP) dominated by inflammatory cytokines, growth factors and proteases, hindering tissue regeneration and promoting chronic inflammation.
- SunYu and his team first screened from the natural medicine Bank (PDMA) and found that grape seed extract (GSE) can destroy senescent cells senolytics. The target compound was on procyanidin C1.
- Previous studies have found that proanthocyanidins in grape seeds have biological activities such as reducing oxidative damage, inhibiting inflammatory response, and inducing cancer apoptosis. Among them, procyanidin C1 can also induce DNA damage, cell cycle arrest and increased expression of checkpoint protein kinases, and induce cancer apoptosis by regulating the activity of Bcl-2, caspases 3, caspases 9 and other pro apoptotic factors. So, will it also have a hand in inducing senescence apoptosis?
- The results of in vitro experiments showed that procyanidin C1 can efficiently induce senescent apoptosis without affecting proliferating cells. It has shown the effect of senolytics at a low concentration (50 μ m). When the concentration is ≤ 200 μ m, the survival rate of senescent cells is lower as the concentration increases. .
- Further, it was found in a variety of human cell models (human fetal lung fibroblasts, human umbilical vein endothelial cells, human mesenchymal stem cells) that procyanidin C1 can effectively induce various types of aging apoptosis caused by Different Inducements, without toxicity to proliferating cells.
- According to transcriptome analysis, a large number of SASP factors were significantly downregulated in senescent cells treated with procyanidin C1, while a variety of Pro apoptotic factors such as noxa and puma were significantly upregulated. . In other words, the proapoptotic factors noxa and puma greatly assisted the "strangulation" of procyanidin C1 on senescent cells.
- Moreover, although procyanidin C1, as a member of the procyanidin family, is very friendly to proliferating cells, can increase cell viability, reduce reactive oxygen species content and reduce oxidative damage, it has some "double labeling" for senescent cells.
- Researchers found that procyanidin C1 could damage the mitochondrial functional integrity of aging cells, resulting in a significant decrease in mitochondrial membrane potential, cytochrome c released from mitochondria into the cytoplasm, and the content of free radicals such as reactive oxygen species in cells not only did not decrease, but increased.
- In vivo experiments. Procyanidin C1 treatment can effectively eliminate senescent cells in mice (c57bl/6j). In all in vivo experiments, it was not observed that urea, creatinine, liver enzymes, body weight and immune function of mice were significantly affected.
- . For older mice aged 24-27 months (≈ 75-90 years of human), the remaining healthy life span after treatment was 64.2% longer than that of the control group mice (equivalent to 9.4% longer overall life span), and the risk of death was reduced by 35% (P
- What is more surprising is that the combination of procyanidin C1 and mitoxantrone (MIT), a chemotherapeutic drug, has an extraordinary anticancer effect.
- The researchers found that the tumor size and survival time of mice (NOD-SCID) were not significantly improved when receiving procyanidin C1 monotherapy. When the mice were treated with procyanidin C1 combined with MIT, the tumor size was reduced by 55.2% and the median survival time was prolonged by 48.1% compared with MIT monotherapy; Compared with the placebo group, the tumor of mice shrank by 74.9%.
- Sun Yu and his team explained that this is because senescent cells have a cancer promoting effect. After chemotherapy, senescent cells in tumors will increase significantly, and Procyanidin C1 treatment can remove them in time. Therefore, although procyanidin C1 treatment alone can neither inhibit tumor growth nor prolong survival, the combination treatment with chemotherapy drugs can burst sparks and strengthen the therapeutic effect of chemotherapy drugs.
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