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Senolytic
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. 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. According to reviews, it is thought that senolytics can be administered intermittently while being as effective as continuous administration. This could be an advantage of senolytic drugs and decrease adverse effects, for instance circumventing potential off-target effects. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cellular Senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrom ... [...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 can be found in many plants, where it serves as a yellow/ochre colouring agent. It is also 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. The biological activity of fisetin has been studied in many laboratory assays; like other polyphenols it has many activities. Biological sources Fisetin can be found in a wide variety of plants. It is found in Eudicotyledons, such as trees and shrubs in the family Fabaceae, such as the acacias ''Acacia greggii'' and ''Acacia berlandieri'', the parrot tree ('' Butea frondosa''), the 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 with myricetin, fisetin provides the color of the tra ... [...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 ... [...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 from ... [...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 can be found in many plants, where it serves as a yellow/ochre colouring agent. It is also 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. The biological activity of fisetin has been studied in many laboratory assays; like other polyphenols it has many activities. Biological sources Fisetin can be found in a wide variety of plants. It is found in Eudicotyledons, such as trees and shrubs in the family Fabaceae, such as the acacias ''Acacia greggii'' and ''Acacia berlandieri'', the parrot tree ('' Butea frondosa''), the 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 with myricetin, fisetin provides the color of the tra ... [...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 ... [...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 cell ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FOXO4
Forkhead box protein O4 is a protein that in humans is encoded by the ''FOXO4'' gene. Structure and function FOXO4 is a member of the forkhead family transcription factors O subclass, which is characterized by a winged helix domain used for DNA binding. There are 4 members of the FOXO family, including FOXO1, FOXO3, and FOXO6. Their activity is modified by many post translational activities, such as phosphorylation, ubiquitination, and acetylation. Depending on this modified state, FOXO4 binding affinity for DNA is altered, allowing for FOXO4 to regulate many cellular pathways including oxidative stress signaling, longevity, insulin signaling, cell cycle progression, and apoptosis. Two of the main upstream regulators of FOXO4 activity are phosphoinositide 3- kinase (PI3K) and serine/threonine kinase AKT/PKB. Both PI3K and AKT modify FOXO4 and prevent it from translocating to the nucleus, effectively preventing the transcription of the downstream FOXO targets. Clinical signif ... [...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 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 suppressor function for th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Piperlongumine
Piperlongumine (also called piplartine or piperlongumin) is an amide alkaloid constituent of the fruit of the long pepper (''Piper longum''), a pepper plant found in southern India and southeast Asia. When extracted, piperlongumine may cause skin, eye or respiratory tract irritation. Traditional medicine and research Long peppers have been used in Ayurveda and traditional Chinese medicine as a supposed treatment. Targtex, a biotechnology spin-off of the Portuguese Institute for Molecular Biology, developed a piperlongumine hydrogel that is to be applied after the removal of Glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ... tumours, with the goal of neutralizing remaining cancer cells. The hydrogel was effective in laboratory and animal studies and is scheduled for Ph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Azithromycin
Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections. Along with other medications, it may also be used for malaria. It can be taken by mouth or intravenously. Common side effects include nausea, vomiting, diarrhea and upset stomach. An allergic reaction, such as anaphylaxis, QT prolongation, or a type of diarrhea caused by ''Clostridium difficile'' is possible. No harm has been found with its use during pregnancy. Its safety during breastfeeding is not confirmed, but it is likely safe. Azithromycin is an azalide, a type of macrolide antibiotic. It works by decreasing the production of protein, thereby stopping bacterial growth. Azithromycin was discovered in 1980 by the Yugoslav pharmaceutical company Pliva and approved f ... [...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 milligrams. 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 presen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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