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Author: Christoffer Mikael Lyckholm Skeneby
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“Dasatinib, often used in combination with quercetin (D+Q), acts as a senolytic by selectively inducing apoptosis in senescent cells by interfering with pro-survival mechanisms. Specifically, dasatinib inhibits tyrosine kinases and targets senescent adipocyte progenitor cells, while quercetin targets anti-apoptotic proteins like BCL-2 and BCL-xL, and modulates pathways such as PI3K/AKT and TP53/P21. This dual action helps clear senescent cells, which contribute to age-related diseases and inflammation by releasing the senescence-associated secretory phenotype (SASP).”
PMC.NCBI
“While dasatinib targets specific pathways, quercetin works in conjunction by inhibiting anti-apoptotic proteins such as BCL-2 and BCL-xL, as well as modulating factors like PI3K/AKT and TP53, further promoting apoptosis in senescent cells. This combination, D+Q, is a well-studied senolytic cocktail used in various research settings to clear senescent cells in different tissues and conditions.”
PMC.NCBI
1: HealthSpan
2: Autophagy
3: Mitophagy
4: Old Skin And The Rest Of The Bodys Cells
5: Collagen and other skin structures
6: Anti-inflammatory
7: Fisetin attenuates periodontitis
8: Cancer
9: Arthritis
10: Eye Sight
11. Blood Vessel Dilation – Lowering your blood pressure
12: Brain
Super Flavonoid Quercetin Supplements
- Liposomal Fisetin with Quercetin
- Lots Of Apples – It’s better to take as a supplement
Quercetin is one of the most potent flavonoids, reactivating autophagy. This allows healthy cells to thrive. This also helps remove toxic elements that accumulate in cells. Moreover, this improves antioxidant activity, suppresses inflammation, and promotes nerve growth.
“Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697716/#:~:text=Flavonoids%20are%20phytochemical%20compounds%20present,%2Dinflammatory%2C%20and%20antiviral%20properties.
Nature.com below!
“interventions targeting those senescent cells that are persistent and cause tissue damage have been shown to delay, prevent or alleviate multiple disorders”
https://www.nature.com/articles/s41591-022-01923-y
1: HealthSpan
“Adding fisetin to your everyday life is one step closer to improving your longevity and reversing ageing. Through numerous clinical studies, Fisetin has shown abilities to aid in obesity and diabetes, support brain health, and enhance skin appearance. It also presents a wide array of potential health benefits across our body systems that is still under research.” https://longevity.technology/lifestyle/what-is-the-best-way-to-take-fisetin/amp/
“Old mice given fisetin had a nearly 10% increase in lifespan.” https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30373-6/fulltext
Observe: If you combine the Top Supplements Etc. and Other Supplements Etc. Listed on HealthSpan/Collagen Synthesis {Natural Herbs + Energy} you can improve your health span.
From the study above: The same was given o old mice that were the human equivalent of 75 years of age, they lived an average of 2.5 months longer. Almost 10% increase in lifespan. Other Studies have found between 0-10% increase in longevity and lifespan.
2: Autophagy
A molecule named chloroquine, responsible for removing autophagy, struggled when Fisetin was added. Furthermore, Fisetin activated autophagy and alleviated the skin disease psoriasis in this case. See the second quote for more information on the latter.
“Western blot analysis and immunofluorescence assay showed that fisetin decreased microtubule-associated protein 1 light-chain 3B (LC3B) and lysosome-associated membrane protein 1 (LAMP1) expression in LPS-treated cells, while the autophagy inhibitor chloroquine (CQ) could partially reverse this effect. In addition, fisetin reduced the elevated expression of p-PI3K, p-AKT and p-mTOR induced by LPS in a concentration-dependent manner.” https://pubmed.ncbi.nlm.nih.gov/33841067/
“We conclude that fisetin potently inhibits IL-17A and the Akt/mTOR pathway and promotes keratinocyte differentiation and autophagy to alleviate IMQ-induced psoriasis-like disease in mice.” https://www.frontiersin.org/articles/10.3389/fimmu.2022.1075804/full
3: Mitophagy
Mitophagy is the selective degradation of mitochondria by autophagy. Because Fisetin supports autophagy, it may also support mitophagy. It’s unclear whether it supports only general autophagy or the whole process. The studies below support the previous one by examining all cell components from different perspectives.
“we found fisetin significantly improved cognitive dysfunction in rats […] Collectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1β into CNS” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739041/
“Treatment of cells with fisetin leads to an increase in the expression of marker proteins of mitophagy” https://www.oaepublish.com/articles/2574-1209.2022.20
4: Old Skin And The Rest Of The Bodys Cells
This is huge for skin care. Works for me – see image above. Moreover Fisetin removes aged skin cells that accumulate in all layers and prevents cell division. It also means that the collagen is newly formed to a higher degree when the cells that are responsible for it in the dermis layer are replaced and the cells thrive in the cell culture, i.e. the surrounding skin cells in all layer.
If aging cells accumulate, they release toxins and other things that give aged skin. The last Fisetin prevents.
”Fisetin selectively eliminated senescent dermal fibroblasts in both senescence-induced cellular models; this effect is attributable to cell death induction by caspases 3, 8, and 9-mediated endogenous and exogenous apoptosis.” https://link.springer.com/article/10.1007/s10522-023-10064-9
5: Collagen and other skin structures
As demonstrated in that heading and paragraphs above – 4: Old Skin And The Rest Of The Bodys Cells = Fisetin removes old cells in particular and specifically in the skin layers. This also affects collagen production.
”Fisetin-treated senescent human skin grafts showed increased collagen density and decreased senescence-associated secretory phenotypes (SASP)”
https://link.springer.com/article/10.1007/s10522-023-10064-9
6: Anti-inflammatory
“Quantitative real-time polymerase chain reaction and Bio-Plex analysis indicated that fisetin decreased the expression and secretion of several inflammatory cytokines in cells administered with LPS.” https://pubmed.ncbi.nlm.nih.gov/33841067/
“Overall, the results of this study provide new clues for the anti-inflammatory mechanism of fisetin and explain the crosstalk between autophagy and inflammation to some extent.” https://pubmed.ncbi.nlm.nih.gov/33841067/
7: Fisetin attenuates periodontitis
“Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway” https://www.sciencedirect.com/science/article/abs/pii/S1567576921001417?via%3Dihub
“As a result, Fisetin reduced the alveolar bone gap, reversed histopathological lesion and inhibited serum inflammatory cytokine concentration in periodontitis rats. Fisetin decreased the inflammatory cytokine contents in the supernatant of LPS-induced HGF. The inhibitory effect of Fisetin might be attributed to FGFR1/TLR4/NLRP3 inflammasome pathway both in vivo and in vitro. ” https://www.sciencedirect.com/science/article/abs/pii/S1567576921001417?via%3Dihub
“The antibacterial, anti-inflammatory and antiresorptive effects of flavonoids make them an important factor in the treatment of periodontal disease. Further research in the use of natural medicinal substances of plant origin is an important aspect for the development of modern medicine.”
https://www.jpccr.eu/The-role-of-flavonoids-in-the-treatment-of-periodontal-diseases-literature-review,156979,0,2.html
Quercetin (Quercitrin) are almost identical to Fisetin but the last is more potent. Below Is a study in the trusted journal Nature.
“Quercitrin decreased the release of the inflammatory mediator PGE2 and partially re-established the impaired collagen metabolism induced by IL-1β treatment in hGFs. Quercitrin also increased ALP activity and mineralization in hMSCs, thus, it increased hMSCs differentiation towards the osteoblastic lineage. These findings suggest quercitrin as a novel bioactive molecule with application to enhance both soft and hard tissue regeneration of the periodontium.” https://www.nature.com/articles/srep16593
8: Cancer
“relatively low dose of fisetin formulation (36.6 mg/kg) was needed to reduce the tumor size by 53% compared to free fisetin (223 mg/kg).” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532335/
9: Arthritis
Fisetin has many good areas of application for alleviating and postponing illnesses. Below is a demonstration of how it works with bone loss and osteoarthritis.
“Flavonoids may modulate the bone formation process. Among flavonoids, fisetin is known to counteract tumor growth, osteoarthritis, and rheumatoid arthritis. In addition, fisetin prevents inflammation-induced bone loss.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149166/
“By testing fisetin in vivo models, it has been demonstrated that it can counteract tumor growth (Khan et al., 2008b), osteoarthritis (Zheng et al., 2017), and rheumatoid arthritis (Léotoing et al., 2013).” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149166/
10: Eye Sight
I have got perfect vision by fisetin. But I took up to 17500 mg liposomal of the same. See the following studie of AMD
“Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. […] Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664957/
“The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664957/
11: Blood Vessel Dilation – Lowering your blood pressure
Vasodilation is the widening of your blood vessels. When blood vessels in your body widen the same allowing more blood to flow through them and also lowering your blood pressure. Take the following study. Better than medicine in my opinion but I can’t back up that statement.
“Nitric oxide (NO) is an essential component of the human body, involved in blood vessel dilation, stimulation of hormone release, signalling and regulation of neurotransmission” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710401/
“Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production,” https://www.mdpi.com/1420-3049/19/7/8820
12: Brain
Together with Lithium, Fisetin can be a revolution to brain health as it removes old cells of various kinds. Only a few of the same were left of a certain type according to the study. Then new brain cells can grow and the environment will be health for the cell culture. Promising but It’s too early to give it a go – The future of research in this area looks promising.
”we found that senescent cells were widely present in the cerebral brain cortex and cerebellum and non-CA area of the hippocampus of old sheep. Fisetin treatment significantly decreased senescent neurons, astrocytes, and microglia in both gray and white matter of the cerebral brain cortex and non-CA area of the hippocampus” https://pubmed.ncbi.nlm.nih.gov/37t627641/
” Fisetin treatment significantly decreased the number of SA-β-Gal+ cells in brain cortex white matter and GL13+ cells in the non-CA area of the hippocampus, and showed a decreasing trend of SA-β-Gal+ cells in the gray matter of both the cerebral brain cortex and cerebellum.” https://www.mdpi.com/2076-3921/12/8/1646
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