Research Features, Год журнала: 2021, Номер 139
Опубликована: Сен. 15, 2021
Язык: Английский
CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)
Опубликована: Окт. 1, 2024
Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.
Язык: Английский
Процитировано
6
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5332 - 5332
Опубликована: Май 14, 2024
The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, role senescent cells in microenvironment still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence. Mesenchymal stem (MSCs) play a pivotal maintaining homeostasis. A multitude studies have examined cytokine profile that determine their regulatory function. extracellular matrix (ECM) MSCs less studied aspect biology. It has been shown modulate activity neighboring cells. Therefore, investigating age-related MSC matrisome crucial for understanding mechanisms niche ageing. This study conducted broad proteomic analysis separated fractions MSCs, including ECM, conditioned medium (CM), lysate. first time such an conducted. established there shift production towards molecules significant downregulation main structural adhesion proteins particularly collagens, fibulins, fibrilins. Additionally, decrease levels cathepsins, galectins, S100 proteins, other with cytoprotective, anti-inflammatory, antifibrotic properties observed. However, level inflammatory regulators profibrotic pathways increases. upregulation can directly cause prosenescent effects on microenvironmental (SERPINE1, THBS1, GDF15). These confirm negative impact niche, not only through signals but also remodeled ECM.
Язык: Английский
Процитировано
4
Biogerontology, Год журнала: 2025, Номер 26(2)
Опубликована: Фев. 13, 2025
Cellular senescence is a stable cell cycle arrest that occurs in response to various stress stimuli and affects multiple types, including endothelial cells (ECs). Senescent accumulate with age, their removal has been linked reduced age-related diseases. However, some senescent are important for tissue homeostasis. Therefore, understanding the diversity of cell-type-specific manner underlying molecular mechanisms essential. Senescence impairs key ECs functions which necessary vascular homeostasis, leading dysfunction In order gain insights into these mechanisms, we analyzed publicly available RNA-seq datasets identify gene expression changes induced by doxorubicin, irradiation, replication exhaustion. While only few genes were consistently differentially expressed across all conditions, ontologies (GO) shared. Among these, our analysis focused on validating associated matrisome, includes encoding extracellular matrix (ECM) structural components ECM-associated proteins, doxorubicin-induced model. Our results show matrisome transcriptome undergoes significant remodeling cells, regardless specific inducers senescence, highlighting importance how ECM alterations affect senescence.
Язык: Английский
Процитировано
0
Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 315 - 359
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Frontiers in Aging, Год журнала: 2025, Номер 6
Опубликована: Март 28, 2025
Introduction: Aging results in an accumulation of damaged cells, which reduces the health tissues and their regenerative capabilities. In skin, there are both internal external drivers oxidative stress that result aging phenotypes. Oxidative has been used to model senescence vitro; however, a lack research determining whether severity correlates with senescent Methods: this work, we compare cellular secretory responses single (500 μM hydrogen peroxide, 2 hours) or recurring dose peroxide hours + 4 × 300 each 48 hours). Senescence induction was studied using markers including cell morphology, senescence-associated-beta-galactosidase, absence apoptosis, cycle inhibition genes. Next, functional studies effects signaling these cells were completed, such as vascular potential, keratinocyte proliferation, macrophage polarization. Results: Fibroblasts exposed had increased total nucleic area, senescence-associated-beta-galactosidase (SABGAL) expression, they able escape apoptosis - all characteristics cells. Additionally, expressed levels inhibitor genes decreased expression collagen-I, -III, -IV. Cytokine profiling showed stressed more inflammatory profile. However, assays, reduced IL-1β gene unpolarized polarized macrophages. Discussion: The described protocol allows for investigation direct fibroblasts on surrounding healthy These show recurringly represent intense phenotype, can be vitro understand responses.
Язык: Английский
Процитировано
0
Cells, Год журнала: 2025, Номер 14(8), С. 608 - 608
Опубликована: Апрель 17, 2025
Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, tumorigenesis. This review examines SASP’s molecular regulation, dual roles in health pathology, therapeutic potential. The following two main strategies are explored: clearance, which eliminates SASP-producing cells, modulation, refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, cGAS-STING, discussed alongside pharmacological, immunotherapeutic, gene-editing, epigenetic interventions. heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, ethical considerations. modulation emerges as promising strategy oncology, repair, with future advancements relying on multi-omics AI-driven insights optimize clinical outcomes.
Язык: Английский
Процитировано
0
Cell, Год журнала: 2025, Номер 188(8), С. 2043 - 2062
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 12
Опубликована: Апрель 24, 2025
Keratoconus is a bilateral and asymmetric degenerative eye disease that causes corneal thinning bowing, leading to irregular astigmatism vision loss. Although environmental genetic factors contribute the disease’s development, exact cause underlying pathological mechanism remain unknown. In this review, we comprehensively explore latest pathophysiological mechanisms of keratoconus, focusing on oxidative damage inflammation. Senescence emerges as key driver keratoconus pathogenesis. Understanding these common elements enhances our understanding paves way for innovative therapeutic approaches keratoconus.
Язык: Английский
Процитировано
0
G3 Genes Genomes Genetics, Год журнала: 2024, Номер 14(4)
Опубликована: Фев. 16, 2024
Abstract Aging is a multifactorial process that disturbs homeostasis, increases disease susceptibility, and ultimately results in death. Although the definitive set of molecular mechanisms responsible for aging remain to be discovered, epigenetic change over time proving promising piece puzzle. Several post-translational histone modifications have been linked maintenance longevity. Here, we focus on lysine-36 replication-independent protein, H3.3 (H3.3K36). To interrogate role this residue Drosophila developmental gene regulation, generated lysine-to-arginine mutant blocks activity its cognate-modifying enzymes. We found an H3.3BK36R mutation causes significant reduction adult lifespan, accompanied by dysregulation genomic transcriptomic architecture. Transgenic co-expression wild-type H3.3B completely rescues longevity defect. Because known accumulate nondividing tissues, carried out transcriptome profiling young vs aged fly heads. The data show loss H3.3K36 age-dependent misexpression NF-κB other innate immune target genes, as well defects silencing heterochromatin. propose maintains postmitotic epigenomic landscape, supporting regulating both pericentric telomeric retrotransposons suppressing aberrant signaling.
Язык: Английский
Процитировано
3
Metabolites, Год журнала: 2024, Номер 14(3), С. 146 - 146
Опубликована: Фев. 28, 2024
Chronic low back pain, a major cause of disability with great global socioeconomic impact, has been inextricably associated intervertebral disc degeneration. On the other hand, an enhanced number senescent cells identified in aged and degenerated discs their senescence-associated secretory phenotype (SASP) connected qualitative/quantitative alterations extracellular matrix ultimately disturbance tissue homeostasis. Given that selective elimination (by so-called senolytics) or amendment secretome towards less catabolic/inflammatory molecules known as senomorphics) reported to alleviate symptoms several age-associated diseases improve quality during aging, here we will review emerging role senolytic senomorphic agents derived from plants natural products against The mode action these senotherapeutics, well challenges practical application, also be explicitly discussed attempt direct more targeted effective use exclusive combinatorial therapeutic schemes for prevention and/or treatment degenerative disorders.
Язык: Английский
Процитировано
2