Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 81, P. 101228 - 101228
Published: March 9, 2025
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 643 - 643
Published: Jan. 4, 2024
The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem—aging, which diminishes the overall quality life. aging process body begins with activation effector signaling pathways cells, resulting loss their normal functions deleterious effects on microenvironment. This, turn, leads chronic inflammation similar transformations neighboring cells. cumulative retention these senescent cells over prolonged period results deterioration tissues organs, ultimately leading reduced elevated risk mortality. Among most promising methods for addressing age-related illnesses are pharmacological, genetic, cellular therapies. Elevating activity aging-suppressing genes, employing specific groups native genetically modified utilizing senolytic medications may offer potential delay ailments long term. This review explores strategies advancements field anti-aging therapies currently under investigation, particular emphasis gene therapy involving adeno-associated vectors cell-based therapeutic approaches.
Language: Английский
Citations
4
Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 348 - 348
Published: Feb. 1, 2024
Our current understanding of skin cell senescence involves the role environmental stressors (UV, O3, cigarette smoke, particulate matter, etc.), lifestyle (diet, exercise, etc.) as well genetic factors (metabolic changes, hormonal, etc.). The common mechanism action these is disturbance cellular redox balance characterized by increased free radicals and reactive oxygen species (ROS), when overload intrinsic antioxidant defense system, it can lead to an oxidative stress condition. main mechanisms that activate in involve (1) damage telomeres causing their shortening; (2) oxidation proteomes DNA damage; (3) a lysosomal mass through activity resident enzymes such senescence-associated β-galactosidase (SA-β-gal) other proteins are products activity; (4) expression SASP, particular pro-inflammatory cytokines transcriptionally regulated NF-κB. However, targets ROS on proteome (oxi-proteome), followed telomeres, nucleic acids (DNAs), lipids, proteins, cytoplasmic organelles. As result, cycle arrest pathways, lipid peroxidation, content dysfunctional mitochondria, SASP synthesis occur. Furthermore, cells increases p16INK4A p53 inhibitors Rb CDks, which important for maintaining cycle. also promotes inactivation mTOR-mediated autophagic apoptotic leading senescence. markers alone cannot establish state senescence, multiple analyses encouraged confirmation. An updated more comprehensive approach investigating should include further assays ox-inflammatory molecular pathways consolidate cutaneous
Language: Английский
Citations
4
Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)
Published: June 4, 2024
Abstract Background The aberrant amplification of mammary luminal progenitors is at the origin basal-like breast cancers associated with BRCA1 mutations. Integrins mediate cell–matrix adhesion and transmit mechanical chemical signals that drive epithelial stem cell functions regulate tumor progression, metastatic reactivation, resistance to targeted therapies. Consistently, we have recently shown laminin-binding integrins are essential for expansion differentiation in physiological conditions. As over-expression α6 integrin (Itgα6) poor prognosis reduced survival cancer, here investigate role Itgα6 tumorigenesis. Methods We used Blg-Cre; Brca1 F/F ; Trp53 mice, a model phenocopies human cancer generated mutant mice proficient or deficient expression followed formation. Mammary tumors pretumoral tissues were characterized by immunohistochemistry, flow cytometry, RT-qPCR, Western blotting organoid cultures. Clonogenicity from preneoplastic glands was studied 3D Matrigel Results show Itga6 deletion favors activation p16 cycle inhibitor tissue. Subsequently, progenitors, Brca1-deficient tumors, restrained Itgα6-deficient gland. In addition, partial EMT program operating Brca1/p53-deficient epithelium attenuated absence Itgα6. consequence these events, formation delayed mice. After formation, lack does not affect growth but rather alters their differentiation, resulting basal markers. Conclusions Our data indicate has pro-tumorigenic developing tumors. particular, reveal required progenitor precedes
Language: Английский
Citations
4
Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 226 - 226
Published: Feb. 5, 2025
The occurrence and severity of periodontitis (PD) tend to increase with age, yet the underlying mechanisms remain unclear. Immune senescence is known be triggered in mice humans as they age. Experimental PD has been shown induce biomarkers p16 INK4a p21, dysfunction antigen-presenting cells (APCs), activation senescence-associated secretory phenotype (SASP). However, causal links experimental are not established. This study aims elucidate role at a level. P16-3MR mouse model harbors p16INK4a (Cdkn2a) promoter, driving vivo expression synthetic Renilla luciferase, monomeric red fluorescent protein (mRFP), herpes simplex virus-1 thymidine kinase (HSV-TK). facilitates identification cellular level consequences selective elimination p16INK4a-positive by ganciclovir (GCV) treatment. Mice were treated with/without GCV for two weeks during ligature-induced PD. In bioluminescence imaging quantified activation, while Western blot immunofluorescence analyses assessed key inflammatory markers (p16, p53, Cyclin D1, p-H2A.X, IL17, IL1β). Alveolar bone volume was analyzed micro-CT histomorphometry. Our findings demonstrate that clearance senescent subjected alleviates inflammation mitigates loss. These results suggest pathology, raising future prospect senolytic agents therapeutic intervention
Language: Английский
Citations
0
Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 81, P. 101228 - 101228
Published: March 9, 2025
Language: Английский
Citations
0