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Senolytics
A senolytic (from the words ''senescence'' and ''-lytic'', "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. Removal of senescent cells with senolytics has been proposed as a method of enhancing immunity during aging. A related concept is "senostatic", which means to suppress senescence. Research Possible senolytic agents are under preliminary research, including some which are in early-stage human trials. The majority of candidate senolytic compounds are repurposed anti-cancer molecules, such as the chemotherapeutic drug dasatinib and the experimental small molecule navitoclax. Soluble urokinase plasminogen activator surface receptor have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen rec ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Senescence
Senescence () or biological aging is the gradual deterioration of Function (biology), functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate, death rates or a decrease in fecundity with increasing age, at least in the later part of an organism's biological life cycle, life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can Life extension, extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus ''Hydra (genus), Hydra'' have motivated research into Life extension, delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases. Environmental Gerontogens, factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and proper ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Navitoclax
Navitoclax (previously ABT-263) is an experimental orally active anti-cancer drug, which is a Bcl-2 inhibitor similar in action to obatoclax. Mechanism of action Navitoclax inhibits not only Bcl-2, but also Bcl-XL and Bcl-w proteins. Because navitoclax inhibits Bcl-XL, it reduces platelet lifespan, causing thrombocytopenia, and this makes it dose-limiting. Effects against senescent cells In animal studies, navitoclax was found to be a senolytic agent, inducing apoptosis in senescent, but not non-senescent cells. Oral administration of ABT263 to either sublethally irradiated or normally aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. This depletion mitigated total-body irradiation-induced premature aging of the hematopoietic system and rejuvenated the aged hematopoietic stem cells and muscle stem cells in normally aged mice. On September 19, 2018, an article was published in Nature about using th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fisetin
Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It occurs in many plants where it serves as a yellow pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub .... It is found in many fruits and vegetables, such as strawberries, apples, persimmons, onions, and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891. Sources Fisetin is a flavonoid synthesized by many plants such as the trees and shrubs of Fabaceae, acacias '' Acacia greggii'', and '' Acacia berlandieri'', parrot tree ('' Butea frondosa''), honey locust ('' Gleditsia triacanthos''), members of the family Anacardiaceae such as the '' Quebracho colorado'', and species of the genus '' Rhus'', which contains the sumacs. Along wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quercetin
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods. Occurrence Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from ''quercetum'' (oak forest), after the oak genus ''Quercus''. It is a naturally occurring polar auxin transport inhibitor. Quercetin is one of the most abundant dietary flavonoids, with an average daily consumption of 25–50 mg. In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration. One study found that organically grown tomatoes had 79% more quercetin than non-organically grown fruit. Quercetin is present in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dasatinib
Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth. Common adverse effects include low white blood cells, low blood platelets, anemia, swelling, rash, and diarrhea. Severe adverse effects may include bleeding, pulmonary edema, heart failure, and prolonged QT syndrome. Use during pregnancy may result in harm to the fetus. It is a tyrosine-kinase inhibitor and works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family. Dasatinib was approved for medical use in the United States and in the European Union in 2006. It is on the World Health Organization's List of Essential Medicines. Medical uses Dasatinib is used to treat people with chronic myeloid leukemia and people with acute lymphoblast ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
USP7
Ubiquitin-specific-processing protease 7 (USP7), also known as ubiquitin carboxyl-terminal hydrolase 7 or herpesvirus-associated ubiquitin-specific protease (HAUSP), is an enzyme that in humans is encoded by the ''USP7'' gene. Function Regulation of the p53 tumor suppressor USP7 or HAUSP is a ubiquitin specific protease or a deubiquitylating enzyme that cleaves ubiquitin from its substrates. Since ubiquitylation (polyubiquitination) is most commonly associated with the stability and degradation of cellular proteins, HAUSP activity generally stabilizes its substrate proteins. HAUSP is most popularly known as a direct antagonist of Mdm2, the ubiquitin ligase, E3 ubiquitin ligase for the tumor suppressor protein, p53. Normally, p53 levels are kept low in part due to Mdm2-mediated ubiquitylation and degradation of p53. In response to oncogenic insults, HAUSP can deubiquitinate p53 and protect p53 from Mdm2-mediated degradation, indicating that it may possess a tumor suppress ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Src Inhibitor
Src inhibitor is a class of inhibitors that targets the Src kinase family of tyrosine kinase, which is transcribed by the Src gene, Src Oncogene, proto-oncogene (short for "sarcoma gene") that potentially induce malignant transformations of certain cells. Because of the crucial position of the Src gene, Src kinase in cells, Src inhibitors are potential antineoplastic agents for e.g. pancreatic cancer, breast cancer and stomach cancer Examples * Tirbanibulin is an oral src inhibitor and the first clinical inhibitor with GI50 of 9–60 nM in cancer cell lines. * Bosutinib has been developed for the treatment of chronic myelogenous leukemia by Pfizer. * Saracatinib, the first Src inhibitor to show inhibition of the Src pathway in human tumor tissue, has anti-tumor activity alone or in combination with chemotherapeutic agents. * PP1, PP2 (kinase inhibitor) are both inhibitors of Lck and FynT. * Dasatinib References {{reflist Antineoplastic drugs Enzyme inhibitors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bcl-xL
B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a member of the Bcl-2 family of proteins, and acts as an anti-apoptotic protein by preventing the release of mitochondrial contents such as cytochrome c, which leads to caspase activation and ultimately, programmed cell death. Function It is a well-established concept in the field of apoptosis that relative amounts of pro- and anti-survival Bcl-2 family of proteins determine whether the cell will undergo cell death; if more Bcl-xL is present, then pores are non-permeable to pro-apoptotic molecules and the cell survives. However, if Bax and Bak become activated, and Bcl-xL is sequestered away by gatekeeper BH3-only factors (e.g. Bim) causing a pore to form, cytochrome c is released leading to initiation of caspase cascade and apoptotic events. While the exact signaling pathway of Bcl-xL is still not known, it is believed that Bcl-xL differs highly fr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quercetin
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods. Occurrence Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from ''quercetum'' (oak forest), after the oak genus ''Quercus''. It is a naturally occurring polar auxin transport inhibitor. Quercetin is one of the most abundant dietary flavonoids, with an average daily consumption of 25–50 mg. In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration. One study found that organically grown tomatoes had 79% more quercetin than non-organically grown fruit. Quercetin is present in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fisetin
Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It occurs in many plants where it serves as a yellow pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub .... It is found in many fruits and vegetables, such as strawberries, apples, persimmons, onions, and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891. Sources Fisetin is a flavonoid synthesized by many plants such as the trees and shrubs of Fabaceae, acacias '' Acacia greggii'', and '' Acacia berlandieri'', parrot tree ('' Butea frondosa''), honey locust ('' Gleditsia triacanthos''), members of the family Anacardiaceae such as the '' Quebracho colorado'', and species of the genus '' Rhus'', which contains the sumacs. Along wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Human Umbilical Vein Endothelial Cell
Human umbilical vein endothelial cells (HUVECs) are cells derived from the endothelium of veins from the umbilical cord. They are used as a laboratory model system for the study of the function and pathology of endothelial cells (e.g., angiogenesis). They are used due to their low cost, and simple techniques for isolating them from umbilical cords, which are normally resected after childbirth. HUVECs were first isolated and cultured ''in vitro'' in the 1970s by Jaffe and others. Jiménez, N., Krouwer, V. & Post, J. A new, rapid and reproducible method to obtain high quality endothelium in vitro. Cytotechnology 65, 1-14 (2012). HUVECs can be easily made to proliferate in a laboratory setting. Like human umbilical artery endothelial cells they exhibit a cobblestone phenotype when lining vessel walls. Inhibition of the sirtuin protein sirtuin 1 (SIRT1) in HUVECs has been shown to induce cellular senescence. Conversely, overexpression of SIRT1 in HUVECs has been shown to inhibit cel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
