134 results about "Senescent cell" patented technology

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 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 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.

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.

This invention discloses a mitochondrial-targeted nanomaterial for senescent cells and its application in anti-aging. The material is a nucleic acid aptamer-tetrahedral DNA, mainly assembled from four single-stranded DNA sequences, SEQ ID Nos. 1-4. Preparation involves first hybridizing the four single-stranded DNA sequences, then concentrating them to obtain aptamer-modified tetrahedra, which are then coupled with tannic acid (TA) via a Mann reaction in the presence of formaldehyde to obtain the Apt-tFNAs-TA complex. Finally, it is incubated with excess catechins to obtain the final delivery material, Apt-tFNAs@catechin-TA. This invention's material exhibits good biocompatibility and skin tissue compatibility, significantly improving uptake efficiency and mitochondrial localization ability in senescent cells. It can effectively deliver polyphenolic compounds such as catechins and protocatechuic acid, improving mitochondrial function and addressing the technical problems of low delivery efficiency of active ingredients and insufficient targeted enrichment in senescent cells.

Disclosed herein are topical compositions comprising Centella asiatica extract and mandelic acid, wherein the compositions have a pH of less than 5, and methods of using the compositions to decrease cellular senescence in skin and treat dermatoporosis. Topical compositions comprising Centella asiatica extract and mandelic acid are effective to reduce the number of senescent cells in mammalian dermis, reduce the senescence-associated secretory phenotype (SASP), downregulate at least one SASP-associated gene, increase the expression of at least one cell cycle-related gene in dermal fibroblasts, downregulate at least one gene associated with skin inflammation, and increase fibroblast cell turnover.

This invention discloses *Bifidobacterium longum* with anti-aging functions and its applications, belonging to the field of microbial technology. The *Bifidobacterium longum* BBS 02 provided by this invention can promote cell vitality and proliferation, inhibit the high activity of β-galactosidase in senescent cells, and inhibit the high expression of the cyclin-dependent kinase inhibitor gene Cdkn1a, thereby achieving an anti-aging effect. The *Bifidobacterium longum* BBS 02 can be used to prepare edible nutrients or skin nutrients.

This invention proposes a nucleic acid aptamer that specifically binds to human senescent dermal fibroblasts (HDFs), along with its screening, identification, and application. Specific aptamers exhibiting high targeting specificity to human senescent HDFs were screened using Cell-SELEX technology. The three selected candidate aptamers showed binding rates of 57.5%, 86.2%, and 50.7% to senescent HDF cells within the same timeframe, respectively, demonstrating high specificity and targeted binding ability. Furthermore, the aptamer possesses potential for detecting, imaging, and regulating the function of senescent cells, successfully providing a new direction for targeted anti-aging interventions and therapeutic applications.

The invention discloses a p16-OSKM transgenic mouse model and a reprogramming senescence cell construction method and application, and belongs to the technical field of cell biology and regenerative medicine. According to the method, a p16-OSKM hybrid mouse capable of specifically inducing an OSKM factor in a p16 high expression cell is obtained on the basis of hybridization of a p16-Ink4a-CreERT2 transgenic mouse, a Rosa26-CAG-LSL-rtTA3-IRES-mKate2 transgenic mouse and a Col1a1-TRE-OSKM-IRES-mCherry transgenic mouse. The selective activation of the OSKM factor in senescent cells with high expression of p16 can be realized by adding doxycycline into primary embryo fibroblasts separated from the mouse under an in-vitro culture condition, so that the senescent cells enter a cell cycle again and recover division and multiplication capacities. The technology provides an accurate model platform for basic research, and can be used for aging mechanism exploration, cell fate regulation and control, chronic disease treatment, development and screening of anti-aging drugs and the like.

The application discloses an engineered exosome targeting human urokinase-type plasminogen activator receptor uPAR and a preparation method and application thereof. Firstly, a high-affinity anti-human uPAR single-domain antibody VHH is prepared; then, a human umbilical cord mesenchymal stem cell engineering cell line expressing a VHH-PTGFRN fusion protein is constructed, and the engineered exosome is prepared and purified by combining three-dimensional hypoxic culture, chemical induction and size-exclusion chromatography technology. The engineered exosome comprises four comparative samples, wherein the core sample Exo^(VHH / miR) can simultaneously display the anti-uPAR VHH on the membrane surface to realize targeted delivery and enrich miR-193b-3p in the chamber to realize gene silencing, and the synergistic effect of the two can efficiently remove the uPAR high-expression senescent cells and inhibit the senescence-associated secretory phenotype SASP. The engineered exosome has the advantages of standardized preparation process, high yield and high purity, strong targeting, excellent curative effect and good safety, and can be used for preparing a treatment preparation for anti-aging and aging-related diseases, and has important clinical application value.

Described herein is a new mitochondrial peptide. This small peptide is capable of modulating cancer, through a variety of mechanisms including autophagy / apoptosis, reduction of tumor cell viability, inducing inflammatory response in senescent cells and conversion of macrophage cell type. Administration of the peptide, its analogs and derivatives thereof, are likely to be effective treatments for cancer therapy, including generation of synthetic analogs that further enhance or abrogate activity relative to the peptide.

The invention discloses an application of loperamide in preparation of a medicine for treating osteoporosis, and belongs to the field of development of new application of medicines. Loperamide has the effects of inhibiting aging, increasing osteogenic differentiation of bone marrow mesenchymal stem cells and preventing osteoporosis of aged and postmenopausal mice; meanwhile, at the cellular level, loperamide can reduce expression of senescence factors in mouse mesenchymal stem cells, promote senescence cell apoptosis and inhibit cell senescence; and a new choice is provided for the treatment of senescence-related osteoporosis drugs.

Disclosed are methods of producing conditionally active proteins that target senescent cells and are conditionally active in the extracellular environment of senescent cells. The methods include methods of using an evolved protein library and testing using physiological concentrations of bodily fluid components. Also disclosed are conditionally active proteins, antibodies, and antibody fragments for killing or removing senescent cells, conjugates and pharmaceutical compositions using these conditionally active proteins, and methods of treating age-related diseases, conditions, or disorders using the pharmaceutical compositions. Conditionally active proteins can be further evolved, conjugated to other molecules, masked, and reduced in activity by linking cleavable moieties.

The present invention relates to an anti-aging composition comprising a Polygonum cuspidatum extract, or polydatin and 2-methoxystypandrone compounds, having cellular senescence and metabolic function recovery effects. The extract or compounds restore mitochondrial function in senescent cells, improve energy metabolism, activate the autophagy system, and reduce inflammatory factors while improving wrinkles and enhancing skin elasticity factors, thereby restoring senescent cells to a young cellular state. The extract or compounds can be applied as a senomorphic composition and can be readily used as a multifunctional cosmetic composition, pharmaceutical composition, or nutraceutical for anti-aging purposes.

The present invention relates to: a peptide inhibitor, which targets FOXO4-p53 interactions, for removing senescent cells; and a use thereof. The peptide inhibitor according to the present invention is designed on the basis of a p53 transactivation domain (TAD) sequence, thus exhibiting strong selectivity for senescent cells, has a synthesis cost due to being short and having an L-type amino acid configuration, and has the effect of efficiently interfering with FOXO4-p53 interactions despite being short and having an L-type amino acid configuration. Therefore, the peptide inhibitor according to the present invention is expected to be widely used in various health / medical fields requiring the removal of senescent cells.