Grape Seed Extract as an anti-aging treatment

    Various factors affect lifespan and health of which cellular senescence is a crucial influencer. Matured and aged cells accumulate and increase in number as we get older which manifests various age-related conditions such as cardiovascular diseases, skeletal fragility, type 2 diabetes and osteoporosis. A specific chemical, flavonoid extracted from grape seeds extract when applied in old mice extends the life span of these mice by 9%. The chemical destroys old and worn out cells making space for new younger cells. The treatment with this special chemical also seems to positively influence the mice’s physical health and even reduce the size of tumorous growth when used alongside chemotherapy treatments to treat cancer.

    After extensively screening a natural product medicinal library comprising of anti-aging agents, Qixia Xu and his colleagues isolated a flavonoid called procyanidin C1 (PCCI), which plays a crucial role in inhibiting senescence-associated secretory phenotype (SASP) expression at low concentrations. While at higher concentrations the PCCI causes the death of senescent cells via inducing apoptosis.

    Among all the natural products tested for anti-senescence effects, GSE under in vitro conditions could suppress the SASP with maximum efficiency (0.1875ug/ml). Thus when used in a specific concentration range, GSE has the potential to control the pro-inflammatory profile of senescent cells.

    Grape Seed Image Source

    At a GSE concentration of 0.75ug/ml, it can eliminate senescent cells. It was concluded by varying different concentrations of GSE, the viability of proliferating cells was not affected even at the highest concentrations but showed a proportional decline in the percentage of surviving senescent cells with increasing GSE concentration.

    In order to prove the effectiveness of this flavonoid in living animals, scientists injected 171 mice that were all around two years old with either PCCI or a control solution twice a week for the rest of their lives. These experiments established that PCCI is capable of prolonging lifespan by 9% on average.

    PCCI was found to promote tumour regression and also reduce chemoresistance. To find out if PCCI is capable of destroying aged tumour cells caused by chemotherapy various experiments and treatments were performed impersonating clinical conditions which were tolerated by animals with no observed significant changes. The team tested the isolated GSE alongside mitoxantrone, a drug used to treat breast cancer, non-Hodgkin lymphoma and acute myeloblastic leukaemia, among other cancers. The results obtained contribute to the principle that anti-aging agents coupled with traditional chemotherapy possess the potential to positively influence tumour response bypassing severe systemic toxicity.

    The team also tested the combined treatment of PCCI and mitoxantrone in mice that were implanted with human prostate tumours cells. It was observed that the combined treatment of the GSE and the chemotherapy drug was able to shrink the tumour by 75% whereas, chemotherapy alone could only reduce the tumours by 44% on average. The scientists stated that their study on GSE and its effect on cells has opened a new portal for prolonging life span and promoting good health.

    a, Quantification of senescent PSC27 cell survival by SA-β-Gal positivity. GSE was applied to the medium at increasing concentrations. CTRL, control (proliferating) cells; SEN, senescent cells; NS, not significant. P values were calculated by one-way ANOVA with Tukey’s multiple-comparison test. b, Representative images displaying SA-β-Gal staining after treatment of PSC27 cells with different concentrations of GSE. Scale bar, 20 μm. Data are representative of three independent experiments. DMSO, dimethylsulphoxide. c, Survival analysis of control and senescent PSC27 cells upon treatment with GSE (at concentrations of 0.3750, 0.7500, 1.8750, 3.7500, 7.5000 and 15.0000 μg ml−1, respectively). Data are shown as mean ± s.d. and were derived from three biological replicates (n = 3 independent assays). P values were calculated by two-sided t-tests. d, Time course measurement of in vitro viability upon treatment of control and senescent PSC27 cells with GSE (3.75 μg ml−1). Data are shown as mean ± s.d. and were derived from three biological replicates (n = 3 independent experiments). P values were calculated by two-sided t-tests. e, Flow cytometry measurement of control and senescent PSC27 cells after processing with an annexin V–FITC and propidium iodide (PI) kit and 4,6-diamidino-2-phenylindole (DAPI) staining to determine the extent of apoptosis. Q1–Q4, quartiles 1–4. f, Comparative quantification of the percentage of viable (Q4, PIannexin V) and apoptotic (Q2 and Q3, PI+annexin V+ and PIannexin V+, respectively) cells in control or senescent populations treated with vehicle or GSE for 3 d (n = 3 biologically independent assays). P values were calculated by two-sided t-tests. g, Measurement of the fluorescence signal of MitoSOX Red, a mitochondrial superoxide indicator, in PSC27 cells under different conditions. P values were calculated by two-sided t-tests. h, High-resolution mass spectra showing the total ion chromatogram (TIC) and base peak chromatogram of GSE after performing HPLC–ESI-QTOF-MS. Unless otherwise indicated, cells were subjected to relevant analyses 3 d after GSE treatment in the culture condition. cps, counts per second. Data in bar graphs and regression curves are shown as mean ± s.d. and are representative of three biological replicates. NS, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.
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    Treatment of age-related pathologies using senotherapeutic agents (combining senolytic and senomorphic potential) which is derived from natural sources have prominent potency. The observation that the extracted chemical did not alter healthy cells and had tremendous selectivity of only acting on aged tumour cells, suggests that it could have potential success in the world of anti-aging therapeutic treatment. The potential anti-aging outcomes of PCCI in various preclinical assays performed by the scientists bestow established grounds for future translational as well as clinical development of PCCI, working towards the overall enhancement of health.

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

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