Biogerontology, Год журнала: 2023, Номер 24(5), С. 679 - 708
Опубликована: Июль 10, 2023
Язык: Английский
Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(7), С. 499 - 515
Опубликована: Фев. 21, 2022
Язык: Английский
Процитировано
987
Journal of Extracellular Vesicles, Год журнала: 2021, Номер 10(12)
Опубликована: Окт. 1, 2021
Cellular senescence is a persistently hypoproliferative state with diverse stressors in specific aging microenvironment. Senescent cells have double-edged sword effect: they can be physiologically beneficial for tissue repair, organ growth, and body homeostasis, pathologically harmful age-related diseases. Among the hallmarks of senescence, SASP, especially SASP-related extracellular vesicle (EV) signalling, plays leading role transmission via paracrine endocrine mechanisms. EVs are successful intercellular interorgan communication microenvironment They detrimental effects on downstream targets at levels immunity, inflammation, gene expression, metabolism. Furthermore, obtained from different donors also promising materials tools antiaging treatments used regeneration rejuvenation cell-free systems. Here, we describe characteristics cellular microenvironment, concentrating production function diseases, provide new ideas therapy EVs.
Язык: Английский
Процитировано
126
Biogerontology, Год журнала: 2023, Номер 24(5), С. 609 - 662
Опубликована: Июль 30, 2023
Язык: Английский
Процитировано
75
The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(4)
Опубликована: Фев. 22, 2024
Cellular senescence is a critical stress response program implicated in embryonic development, wound healing, aging, and immunity, it backs up apoptosis as an ultimate cell-cycle exit mechanism. In analogy to replicative exhaustion of telomere-eroded cells, premature types senescence—referring oncogene-, therapy-, or virus-induced senescence—are widely considered irreversible growth arrest states well. We discuss here that entry into full-featured not necessarily permanent endpoint, but dependent on essential maintenance components, potentially transient. Unlike binary state switch, we view with its extensive epigenomic reorganization, profound cytomorphological remodeling, distinctive metabolic rewiring rather journey toward condition variable strength depth. Senescence-underlying maintenance-essential molecular mechanisms may allow reentry if continuously provided. Importantly, senescent cells resumed proliferation fundamentally differ from those never entered senescence, hence would reflect reversion dynamic progression post-senescent comes distinct functional clinically relevant ramifications.
Язык: Английский
Процитировано
33
Redox Biology, Год журнала: 2024, Номер 70, С. 103048 - 103048
Опубликована: Янв. 17, 2024
The redox process and cellular senescence are involved in a range of essential physiological functions. However, they also implicated pathological processes underlying age-related neurodegenerative disorders, including Alzheimer's disease (AD). Elevated levels reactive oxygen species (ROS) generated as result abnormal accumulation beta-amyloid peptide (Aβ), tau protein, heme dyshomeostasis is further aggravated by mitochondria dysfunction endoplasmic reticulum (ER) stress. Excessive ROS damages vital components such proteins, DNA lipids. Such damage eventually leads to impaired neuronal function cell death. Heightened oxidative stress can induce via activation the senescence-associated secretory phenotype exacerbate inflammation tissue dysfunction. In this review, we focus on how changes system contribute AD affected perturbations metabolism mitochondrial function. While potential therapeutic strategies targeting have received some attention, more research necessary bring them into clinical application.
Язык: Английский
Процитировано
26
Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101057 - 101057
Опубликована: Янв. 21, 2024
Язык: Английский
Процитировано
21
Cellular and Molecular Life Sciences, Год журнала: 2021, Номер 78(19-20), С. 6557 - 6583
Опубликована: Авг. 30, 2021
Язык: Английский
Процитировано
82
Antioxidants, Год журнала: 2022, Номер 11(8), С. 1426 - 1426
Опубликована: Июль 22, 2022
The nuclear factor erythroid 2-related 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed this pleiotropic transcription that regulates hundreds genes. After 40 years in-depth research key discoveries, NRF2 is now at center vast regulatory network, revealing signalling increasingly complex. It widely recognized reactive oxygen species (ROS) play role human physiological pathological processes such ageing, obesity, diabetes, cancer, neurodegenerative diseases. high consumption associated with levels free iron oxidizable unsaturated lipids make brain particularly vulnerable oxidative stress. A good stability activity thus crucial maintain redox balance therefore homeostasis. In review, we gathered recent data about contribution pathway healthy well during metabolic diseases, ageing-related We also discuss promising therapeutic strategies need for better understanding cell-type-specific these different fields.
Язык: Английский
Процитировано
45
Cancers, Год журнала: 2023, Номер 15(9), С. 2660 - 2660
Опубликована: Май 8, 2023
Resistance to cancer therapies remains a clinical challenge and an unsolved problem. In previous study, we characterized new colon cell line, namely HT500, derived from human HT29 cells resistant clinically relevant levels of ionizing radiation (IR). Here, explored the effects two natural flavonoids, quercetin (Q) fisetin (F), well-known senolytic agents that inhibit genotoxic stress by selectively removing senescent cells. We hypothesized biochemical mechanisms responsible for radiosensitising these senolytics could intercept multiple pathways signal transduction correlated death resistance. Radioresistant HT500 modulate autophagic flux differently than secrete pro-inflammatory cytokines (IL-8), commonly associated with senescence-related secretory phenotypes (SASP). Q F PI3K/AKT ERK pathways, which promote p16INK4 stability resistance apoptosis, but they also activate AMPK ULK kinases in response at early stage. summary, combination IR activates forms death: apoptosis inhibition ERKs lethal autophagy dependent on kinase. Our study confirms senescence partially overlap, share common modulatory reveal how flavonoids can play important role processes.
Язык: Английский
Процитировано
23
Aging Cell, Год журнала: 2024, Номер 23(5)
Опубликована: Апрель 29, 2024
Abstract Senescence is a heterogenous and dynamic process in which various cell types undergo cell‐cycle arrest due to cellular stressors. While senescence has been implicated aging many human pathologies, therapeutic interventions remain inadequate the absence of comprehensive set biomarkers context‐dependent manner. Polyphenols have investigated as senotherapeutics both preclinical clinical settings. However, their use hindered by limited stability, toxicity, modest bioavailability, often concentration at target sites. To address these limitations, nanocarriers such polymer nanoparticles lipid vesicles can be utilized enhance efficacy senolytic polyphenols. Focusing on widely studied agents—specifically fisetin, quercetin, resveratrol—we provide concise summaries physical chemical properties, along with an overview findings. We also highlight common signaling pathways potential toxicities associated agents. Addressing challenges linked nanocarriers, we present examples senotherapeutic delivery types, without nanocarriers. Finally, continued research development agents are encouraged reduce undesirable effects different organs. This review underscores need for establishing reliable sets that could assist evaluating effectiveness current future candidates
Язык: Английский
Процитировано
13