188 results about "Senescent cell" patented technology

The invention discloses a senescent cell recognition system and method based on mitochondrial morphology. The system is a classification network, and the input data of the system is a distribution image of mitochondria in subcellular level cells, the distribution image of mitochondria in cells, the shape and / or number of mitochondria distributed at different positions in a three-dimensional structure for displaying cells, and preferably the shape and number of mitochondria distributed at different positions in the three-dimensional structure for displaying cells. According to the senescence cell recognition system based on the mitochondrial morphology, the senescence cells jointly show mitochondrial morphological changes including mitochondrial distribution, mitochondrial shapes and mitochondrial number changes, the senescence cell recognition method is easy to conduct through computer vision, good robustness is achieved, and the senescence cell recognition system based on the mitochondrial morphology is suitable for being applied to senescence cell recognition. Compared with other senescence cell identification methods based on cell nucleus morphological characteristics, the senescence cell identification method based on the general characteristics of the senescence cells has good universality for different cell types.

[Problem] To provide a novel ferroptosis-inducing drug, and in particular, to provide a ferroptosis induction promoter that can effectively promote the induction of ferroptosis even in a cell having ferroptosis resistance even in a ferroptosis-inducing environment (for example, cancer cells and senescent cells). [Solution] Provided is a ferroptosis induction promoter comprising a drug that can reduce lysosomal pH.

The present invention belongs to the technical field of gene therapy. Provided are a chimeric antigen receptor nanocomposite and a preparation method therefor and the use thereof in the preparation of an anti-aging drug. The provided chimeric antigen receptor nanocomposite comprises a chimeric antigen receptor DNA plasmid specifically recognizing senescent cells, a polymer coupled with a signal peptide, a free polymer and an antibody polymer targeting T cells, wherein the chimeric antigen receptor DNA plasmid, the polymer coupled with a signal peptide, the free polymer and the antibody polymer targeting T cells are sequentially mixed and incubated to form the chimeric antigen receptor nanocomposite. The chimeric antigen receptor nanocomposite can rapidly generate senescent cell-marked chimeric antigen T cells in vivo. The engineered T cells have the ability to specifically eliminate senescent cells in vivo, and can rapidly and durably eliminate senescent cells in vivo, which is irreplaceable and has wide application prospects.

The invention relates to a repairing composition for reducing senescence cell cumulant and a preparation method and application thereof, and the repairing composition comprises the following components in parts by weight: 0.01-7.0 parts of probiotic pellets PDRN, 0.01-3.0 parts of microspheroidized PDRN, 0.01-10.0 parts of a ginseng root extract, 0.01-10.0 parts of red ginseng fermented vesicles, a thickening agent, functional components and water. Under a formula system of a thickening agent and functional components, the probiotic pellets PDRN, the microspheroidized PDRN, the ginseng root extract and the red ginseng fermented vesicles are added, and all the components have a synergistic effect, so that the composition can penetrate into skin to achieve the effect of accurately repairing mitochondrial dysfunction, can directly remove senescent cells, reduces the senescent cell cumulant in a body in multiple ways, and has a good effect on repairing mitochondrial dysfunction. Therefore, the prepared skin care composition can effectively delay skin aging.

The invention relates to a calcium homeostasis disruptor in combination with a selective Death Receptor 5 (DR5) agonist for use in a method of treating a patient suffering from a tumour. The invention further relates to a pharmaceutical composition, comprising a calcium homeostasis disruptor in combination with a selective Death Receptor 5 (DR5) agonist and, optionally, an inducer of senescence. The invention further relates to methods of treating a patient having a tumour, and to a calcium homeostasis disruptor in combination with a selective DR5 agonist, for use in a method of selectively killing senescent cells, including senescent cancer cells.

The invention discloses a ternary fusion polypeptide Col-TF-1 targeting senescence cells, a monoclonal antibody mAb SC-1 matched with the ternary fusion polypeptide Col-TF-1, an anti-aging composition containing the ternary fusion polypeptide Col-TF-1 and the monoclonal antibody mAb SC-1, and application of the ternary fusion polypeptide Col-TF-1 The fusion polypeptide is formed by connecting a targeting peptide for targeting a senescence cell surface uPAR receptor, a collagen active peptide for promoting collagen synthesis and an immunomodulatory peptide for activating NK cells in series through a flexible linker GGGGS, and the amino acid sequence is as shown in SEQ ID NO.1. The invention further discloses a preparation method of the fusion polypeptide. Through CDR region humanized reconstruction and pH sensitive histidine switch design, the affinity of the matched antibody mAb SC-1 is improved by 5 times in a subacid environment, and the ADCC effect is enhanced through fucose-deficient host cells. Experiments show that when the fusion polypeptide is combined with the antibody, the senescent cell clearance rate can reach 45.2%, the collagen density is increased by 83.5%, and the effect is obviously superior to that of a single drug. The composition provided by the invention can be applied to the fields of cosmetics, medical instruments, medicines and functional foods, and provides a new strategy for treatment of senescence-related diseases and development of anti-senescence products.

The present invention discloses a photosensitizer prodrug compound (structural formula (I)) that selectively clears senescent cells and is specifically activated by the aging-associated β-galactosidase, as well as its preparation method and application. Upon activation by β-galactosidase, the compound rapidly releases its active molecule, anchoring it to proteins with nucleophilic groups. This allows for precise detection and covalent anchoring of senescent cells, thereby achieving selective clearance of senescent cells, reversing senescence-related markers and gene expression, and ameliorating aging-related decline in bodily functions. #imgabs0#

The invention discloses a preparation method of DRP1 engineered mitochondrial derived vesicles and application of the DRP1 engineered mitochondrial derived vesicles in cell aging resistance. The method comprises the following steps: firstly, constructing a lentiviral vector of an overexpressed DRP1 gene, and transfecting cells to obtain a cell strain of the stable overexpressed DRP1 gene; and culturing the cell strain, collecting a culture solution, and separating and extracting the mitochondrial derived vesicles to obtain the DRP1 engineered mitochondrial derived vesicles DRP1-MDVs rich in mtDNA. The DRP1-MDVs is used for treating senescent cells, the DRP1-MDVs is successfully internalized into senescent cells, the ROS level can be effectively reduced, the mitochondrial mtDNA and ATP content can be improved, the mtDNA mutation rate can be reduced, the mitochondrial membrane potential and the mitochondrial network structure can be recovered, and finally the expression of senescence-related proteins P16 and P21 can be reduced. The obvious mitochondrial function repairing potential and the cell aging improving effect are shown.

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

The present invention relates to the use of GRP78 and peptides similar thereto or nucleic acids encoding the same. The peptides or nucleic acids according to the present invention can increase the expression of biomarkers having reduced expression in senescent cells, and thus can be used to restore the function of muscle tissue that has decreased in function due to aging, etc.

The invention belongs to the technical field of biological medicines, and particularly relates to lipid nanoparticles as well as a preparation method and application thereof. The invention discloses a lipid nanoparticle. The material of the lipid nanoparticle comprises phospholipid and cholesterol. According to the invention, a lipid nano-carrier delivery system entrapped with apoptotic protein Bax is prepared through a microfluidic technology, and high encapsulation rate and stable delivery of protein drugs are realized. The nano-carrier delivery system capable of actively encapsulating the lipidosome realizes targeted delivery to senescent cells in vivo, so that senescent cell apoptosis is effectively induced, the proportion of senescent cells in tissues is reduced, and a new thought and means are provided for anti-aging treatment.

The application discloses a kind of composition with immunoregulation and anti-aging function and preparation method thereof, and core component is marine collagen peptide, fusion polypeptide CPF-1, targeting senescent cell monoclonal antibody mAb Senolix, five gallate acyl glucose (PGG) and Hericium erinaceus polysaccharide.Fusion polypeptide CPF-1 is designed by domain fusion strategy, with collagen binding, immune activation and antibacterial function;Monoclonal antibody mAb Senolix targets the surface antigen p16^(INK4a) of senescent cell, and removes senescent cell by ADCC effect.The composition significantly improves immune cell activity, promotes collagen synthesis and reduces chronic inflammation through the synergistic effect of multiple components, and shows excellent immunoregulation and anti-aging effect in in vitro cell model and immunosuppressed mouse model, and can be used for developing immune enhancer, anti-aging drug or functional food.

The invention relates to the technical field of daily cosmetics, in particular to a peony extract with scalp anti-aging and anti-hair-loss functions and application. The peony extract disclosed by the invention is a peony flower extract, the mass fraction of peony flower peptide in the peony flower extract is greater than or equal to 10%, and the peony extract disclosed by the invention is found to have the effects of improving the activity of superoxide dismutase (SOD) on human hair papilla cells for the first time; the positive cell rate of beta-galactosidase (SA-beta-Gal) of human hair papilla cells is inhibited, and the functions of senescent cells are reduced; meanwhile, the functions of promoting hair follicles to express growth factors and promoting hair growth are achieved. The method can be applied to preparation of scalp care products, and the anti-aging or anti-hair-loss function of scalp is achieved.

The application belongs to the technical field of functional polypeptides, and particularly relates to an active peptide for senescent cells and a preparation method thereof, wherein the active peptide is obtained by molecular docking simulation screening and optimization with a helical structure segment in an IL-6R protein combined with a gp130 protein as a polypeptide template; the active peptide after functional optimization contains an FF unit driving nano self-assembly, a GFLG unit capable of being specifically cut by a lysosome protease highly expressed in a microenvironment of senescent cells, and an RYFQKWEKLRNQ unit generating high affinity with an IL-6 / IL-6R / gp130 complex; the designed active peptide itself has anti-aging activity and can also be used for synergistic delivery of drugs, and has a broad application prospect.

It was discovered that by binding to CTCF which is important for maintaining chromosomal structures, hSATII RNA inhibits the function thereof, changes chromosome interaction, and induces transcription of inflammation-associated genes. It has also been discovered that cell death can be selectively induced in senescent cells and cancer cells by suppressing hSATII RNA expression. From the obtained results, it has been found that cancer treatment which targets senescent stromal cells and cancer cells can be performed with a substance that suppresses hSATII RNA or a substance that increases CTCF expression. In addition, cancer can be detected early by measuring the expression and activity of hSATII RNA and CTCF, and an epigenomic change of the hSATII DNA region. Thus, it is possible to provide a therapeutic drug for a cancer associated with cellular senescence, a method for screening thereof, and a test support method.

The present invention relates to a human pluripotent stem cell-derived senomorphic extracellular vesicle composition for treating cellular senescence and stem cell degeneration. Specifically, the present invention relates to a senomorphic composition comprising stem cell-derived extracellular vesicles as an active ingredient, the composition being characterized by restoring a function or morphology of senescent cells to that of normal cells, and to a pharmaceutical composition comprising the senomorphic composition as an active ingredient for preventing or treating nerve injury and ischemic diseases.

The technology relates in part to compositions containing a cell penetrating peptide that can be used to selectively reduce a senescent cell population. The technology also relates to methods of treatment of ageing and ageing-associated diseases using a cell penetrating peptide to selectively reduce a senescent cell population.

A method and apparatus for selecting microsecond pulsed electric field parameters for killing senescent cells. The method includes: 1) obtaining biological tissue cells and culturing them to obtain n groups of cell reagents containing normal cells and n groups of cell reagents containing senescent cells; 2) setting n groups of pulsed electric field parameters for killing senescent cells; 3) placing the i-th group of cell reagents containing normal cells and the i-th group of cell reagents containing senescent cells between an electrode pair, and electrically stimulating the i-th group of cell reagents containing normal cells and the i-th group of cell reagents containing senescent cells using the i-th group of pulsed electric field parameters; 4) performing cell activity detection, PI positivity rate detection, and electrosensitivity detection on each group of cell reagents after electrical stimulation to determine the optimal pulsed electric field parameters. The apparatus includes an electrode pair and a pulse generator. Compared with traditional treatment methods for chronic wounds, this invention only requires an electric field to efficiently and accurately kill senescent cells, without thermal effects or side effects.

A compound, or a salt or solvate thereof, according to formula I as defined herein and pharmaceutical composition comprising said compound. Compounds of formula I are capable of detecting senescence. As such, these compounds are useful in methods of detecting or imaging senescent cells or extracts thereof or senescence in a subject or a biological sample taken from a subject.

The application discloses an engineered umbilical cord stem cell and application thereof in preparation of anti-aging drugs and medical beauty products. The application constructs an engineered cell system with high anti-aging function by designing a fusion polypeptide TAT-SIRT1-SOD (SEQ ID NO: 1) and an anti-p16INK4a monoclonal antibody (mAb-p16) to cooperatively modify the umbilical cord stem cell, and combining a 3D dynamic culture technology. The fusion polypeptide is mediated to cross the membrane by a TAT cell-penetrating peptide, activates SIRT1 and removes mitochondrial ROS; the mAb-p16 is specifically combined with p16INK4a on the surface of a senescent cell, and removes the senescent cell through an ADCC effect. Experiments show that the engineered umbilical cord stem cell can increase the removal rate of the senescent cell by 86.1%, increase the SOD activity by 300%, significantly inhibit the secretion of an inflammatory factor IL-6, and increase the skin collagen density by 148% and reduce the wrinkle depth by 67% in an animal model. The application provides a novel and efficient technical scheme for anti-aging drugs and medical beauty products.

Senescent cells are implicated in aspects of age-related decline in health and may contribute to certain diseases. Embodiments include formulations and methods for promoting longevity and treating a senescence associated disease or disorder. Applicants present three distinct classes and multiple associated therapeutic molecules that can function alone or in combination with the other molecules. The classes include transcription regulators, lipid intermediates and microRNAs. Additional embodiments include methods of promoting longevity by administering GRAS substances.

Provided is a novel use of a composition that contains S-1-propenyl cysteine and / or a salt thereof.　The present invention can be an eNAMPT increasing agent in which S-1-propenyl cysteine or a salt thereof is an active ingredient. The present invention can be an eNAMPT increasing agent that contains S-1-propenyl cysteine or a salt thereof and that is administered to an animal. Particularly, it is preferable that the present invention be used for increasing eNAMPT in blood.

An ABT-263-loaded drug delivery system comprises a liposome and elemental gold, ABT-263 is loaded in the liposome, and the liposome is coated with the elemental gold to form a gold shell (Lipo-atABT263-atAu). Through verification, the senescent cell scavenger (ABT-263) and the golden shell liposome are integrated together to achieve the purposes of sensitizing radiation and continuously releasing drugs. In in-vitro experiments, the Lipo-ABT263-coated Au enhances cell apoptosis induced by radiation therapy, eliminates radiation-induced senescence tumor cells, and inhibits the tumor promoting effect of senescence-related secretion phenotypes. In an animal model, a drug delivery system remarkably inhibits tumor growth, skin fibrosis induced by radiotherapy is relieved through targeted aging fibroblasts, and systemic toxicity is not shown.

Provided herein are methods of detecting senescent cells using bioresponsive magnetic resonance imaging (MRI) contrast agents.

The invention discloses a targeted multi-channel synergistic anti-aging composition as well as a preparation method and application thereof, and belongs to the technical field of functional foods and biological medicines. According to the composition disclosed by the invention, ginsenoside, a hawthorn polyphenol-chitosan phospholipid complex and spina date seed total saponins are taken as core active ingredients, and a specific Senlytics active ingredient and a natural mTOR inhibitor are compounded, so that the synergistic regulation of five anti-aging pathways, namely Sirtuins activation, mTOR inhibition, mitochondrial autophagy activation, CD38 inhibition and senescent cell removal, can be realized at the same time. The composition is natural in raw material source, high in safety and good in stability, can be prepared into various dosage forms such as capsules, solid beverages and oral liquid, is suitable for daily anti-aging and sub-health conditioning, and has wide application prospects in the fields of anti-aging health foods and biological medicines.

The invention discloses a quercetin nano-vesicle complex as well as a preparation method and application thereof. The preparation method of the nano-vesicles comprises the following steps: separating and purifying extracellular vesicle-like nano-particles from cow milk by combining differential centrifugation with an EDTA precipitation method; quercetin is efficiently loaded in a vesicle nanostructure by adopting an ultrasonic-assisted co-incubation technology, and a drug loading system is characterized through particle size analysis, Zeta potential determination and a transmission electron microscope. The natural lipid bilayer structure of the milk-derived extracellular vesicles is creatively utilized, the constructed quercetin nano-vesicle complex shows excellent stability in simulated gastrointestinal fluid, and the average encapsulation efficiency can reach 60%. In-vitro and in-vivo experiments prove that the nano vesicles can efficiently remove senescent cells. The invention has a wide clinical application prospect in the field of anti-aging and inflammation-related disease treatment.

The invention discloses application of a targeted stimulating molecule in preparation of drugs, health care products and cosmetics for preventing and treating natural aging, and relates to the field of biological medicines. The molecule provided by the invention can mediate the interaction between senescence cells and immune cells, enhance the endogenous immune function, and achieve the purposes of effectively removing senescence cells and improving senescence-related diseases. One end of the functional molecule for targeted senescence cell immune sensitization targets senescence cell membrane molecules, glutamic acid is marked on the surfaces of senescence cells, coupling between endogenous immune cells and the senescence cells is mediated, and adhesion and removal of the senescence cells by the immune cells are promoted. The molecule can regulate the immune microenvironment of senescent tissues, effectively reduce the number of positive senescent cells of senescence-related beta-galactosidase, improve the natural senescence phenotype of an organism and recover the phenotype and function of senescent skin.

This invention discloses a method for preparing NK cells, the NK cells obtained thereby, and their applications. The method includes: sorting NK cells from peripheral blood of an allogeneic donor; culturing them in a serum-free medium containing CD3 monoclonal antibody, CD16 antibody, and IL-2, without the need for a feeder layer; preferably, IL-21 is added for amplification on days 3-5 of culture, and the cells are cultured for 20-40 days. This method yields non-genetically modified NK cells, among which CD56... bright The NK cells comprise >90% of the cell line and highly express a variety of activating and functional molecules. These NK cells effectively clear Aβ oligomers and senescent cells, and alleviate neuroinflammation. In treatment, intracranial injection achieves equivalent or better efficacy with only about 1 / 10th the dose administered intravenously, significantly clearing Aβ deposits in the brains of AD model mice and improving pathology.

Compositions of matter, devices, and treatment protocols for reducing deleterious effects of senescent cells in a mammal. The invention provides extracorporeal devices capable of removing, in some cases selectively, senescence associated factors including small molecules, proteins, lipoproteins, as well as in some embodiments extracellular vesicles including exosomes, apoptotic bodies, or cellular released particles. Extracorporeal removal of senescent cell associated factors is performed to augment effects of senolytic therapy. Removal of senescence associated factors is performed to enhance efficacy of regenerative medicine interventions.

A compound, or a salt or solvate thereof, according to formula I as defined herein and pharmaceutical composition comprising said compound. Compounds of formula I are capable of detecting senescence. As such, these compounds are useful in methods of detecting or imaging senescent cells or extracts thereof or senescence in a subject or a biological sample taken from a subject.