Biogerontology, Год журнала: 2023, Номер 24(5), С. 679 - 708
Опубликована: Июль 10, 2023
Язык: Английский
Aging Cell, Год журнала: 2025, Номер unknown
Опубликована: Фев. 9, 2025
ABSTRACT Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging‐related diseases. It has long been speculated that “rejuvenation molecules” exist in their blood promote extended lifespan. We unexpectedly discovered longevity exhibit erythrocyte oxygen release function similar young individuals, whereas most elderly show reduced capacity. Untargeted metabolomics profiling revealed are characterized by youth‐like metabolic reprogramming these metabolites effectively differentiate the from elderly. Quantification analyses led us identify multiple novel longevity‐related within erythrocytes including adenosine, sphingosine‐1‐phosphate (S1P), glutathione (GSH) related amino acids. Mechanistically, we increased bisphosphoglycerate mutase (BPGM) MFSD2B protein levels of collaboratively work together induce elevation intracellular S1P, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) membrane cytosol, thereby orchestrate glucose toward Rapoport–Luebering Shunt 2,3‐BPG production trigger delivery. Furthermore, glutamine glutamate transporter expression coupled with enhanced metabolism underlie elevated GSH higher anti‐oxidative stress capacity individuals. As such, displayed less systemic hypoxia‐related more antioxidative anti‐inflammatory plasma, healthier clinical outcomes inflammation parameters as well better glucose–lipid metabolism, liver kidney function. Overall, identified youthful enable counteract peripheral tissue thus maintaining healthspan.
Язык: Английский
Процитировано
1
Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)
Опубликована: Март 7, 2025
Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.
Язык: Английский
Процитировано
1
Antioxidants, Год журнала: 2022, Номер 11(3), С. 480 - 480
Опубликована: Фев. 28, 2022
Cell senescence is critical in diverse aspects of organism life. It involved tissue development and homeostasis, as well tumor suppression. Consequently, it tightly integrated with basic physiological processes during On the other hand, gradually being considered a major contributor organismal aging age-related diseases. Increased oxidative stress one main risk factors for cellular damages, thus driver senescence. In fact, there an intimate link between cell response to different types stress. Oxidative occurs when production reactive oxygen species/reactive nitrogen species (ROS/RNS) not adequately detoxified by antioxidant defense systems. Non-coding RNAs are endogenous transcripts that govern gene regulatory networks, impacting both pathological events. Among these molecules, microRNAs, long non-coding RNAs, more recently circular crucial mediators almost all processes, including those implicated responses. Here, we will describe recent data on ROS/RNS-induced current knowledge role program.
Язык: Английский
Процитировано
32
Pharmaceutical Medicine, Год журнала: 2022, Номер 36(6), С. 331 - 352
Опубликована: Сен. 13, 2022
Язык: Английский
Процитировано
30
Molecular Biology Reports, Год журнала: 2023, Номер 50(8), С. 6927 - 6936
Опубликована: Июнь 21, 2023
Язык: Английский
Процитировано
16
Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 279, С. 116461 - 116461
Опубликована: Май 19, 2024
Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat reproductive health. However, exact effects of PS-NPs exposure on testicular cells underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with (80 nm) at different dosages (0, 10, 40 mg/kg/day) for 60 days, GC-1 treated this study. Enlarged seminiferous tubule lumens loose vacuolated layer spermatogenic observed PS-NPs-exposed mice. Spermatogenic which may be one target damage, decreased from group. caused undergo senescence, manifested as elevated SA-β-galactosidase activity activated senescence-related signaling p53-p21/Rb-p16 pathways, induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested key role reactive oxygen species (ROS) PS-NPs-induced result was confirmed by measuring ROS levels. Moreover, inhibition partially attenuated senescence phenotype DNA damage. Using health atlas (MHA) database, Sirt1 filtrated critical molecule regulation senescence. overexpression main generator Nox2, downregulated Sirt1, increased p53 acetylated vivo vitro, whereas these disturbances restored pterostilbene. In addition, pterostilbene intervention significantly alleviated burst. Collectively, our study reveals that can trigger mediated regulating Sirt1/ROS axis. Importantly, promising strategy alleviate
Язык: Английский
Процитировано
6
Chemical Society Reviews, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
This review provides a comprehensive summary of the dysregulation redox metabolism in cancer cells and advantages latest advances nanomaterial-assisted metabolic regulation therapy.
Язык: Английский
Процитировано
6
Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)
Опубликована: Янв. 1, 2021
Mitochondria are the main powerhouse of cell, generating ATP through tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS), which drives myriad cellular processes. In addition to their role in maintaining bioenergetic homeostasis, changes mitochondrial metabolism, permeability, morphology critical cell fate decisions determination. Notably, respiration coupled with passage electrons electron transport chain (ETC) set up a potential source reactive oxygen species (ROS). While low moderate increase intracellular ROS serves as secondary messenger, an overwhelming result either increased production and/or deficient antioxidant defenses is detrimental biomolecules, cells, tissues. Since mitochondria both regulate fate, attention has been drawn involvement various processes carcinogenesis. To that end, link between prooxidant milieu survival proliferation well switch OXPHOS associated recalcitrant cancers provide testimony for remarkable metabolic plasticity important hallmark cancers. this review, regulation redox status by metabolism its implications cancer will be discussed followed significance mitochondria‐targeted therapies cancer.
Язык: Английский
Процитировано
34
Redox Biology, Год журнала: 2022, Номер 51, С. 102282 - 102282
Опубликована: Март 11, 2022
Protein methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues leading to regulation of transcription and splicing programs. Although PRMT5 has emerged as an attractive oncology target, the molecular determinants dependency in cancer remain incompletely understood. Our transcriptomic analysis identified activating factor 4 (ATF4) pathway acute myelogenous leukemia (AML). inhibition resulted expression unstable, intron-retaining ATF4 mRNA that is detained nucleus. Concurrently, decrease spliced cytoplasmic transcript led lower levels protein downregulation target genes. Upon loss functional PRMT5, cells with low displayed increased oxidative stress, growth arrest, cellular senescence. Interestingly, EVI1 oncogene overexpression demonstrated dependence on function. regulated gene signatures were inversely correlated. We show EVI1-high AML have reduced levels, elevated baseline reactive oxygen species sensitivity inhibition. Thus, demonstrate function stress response. Overall, our findings identify PRMT5-ATF4 axis be safeguarding redox balance especially important high states, such those occur overexpression.
Язык: Английский
Процитировано
23
Journal of Ethnopharmacology, Год журнала: 2023, Номер 311, С. 116286 - 116286
Опубликована: Март 23, 2023
Язык: Английский
Процитировано
13