Modulation of gut microbiota, up-regulation of ZO-1, and promotion of metabolism as therapeutic mechanisms of indole-3-carbinol against obesity in mice DOI Creative Commons
Xiaolu Mao,

Guliruoyi Paerhati,

Yu-Che Wu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Indole-3-carbinol (I3C) is a compound derived from Cruciferous vegetables. We aim to ascertain whether I3C mediates the relations between mouse gut microbiota, intestinal barrier function, and metabolism treat obesity in mice. The experimental analyses focused on changes lipid distribution, inflammatory cytokines, glucose tolerance, microbiota composition, serum metabolomics of 60 C57BL/6N results demonstrated that reduced body weight, hepatic steatosis, systemic inflammation improved insulin resistance mice high-fat diet (HFD). Furthermore, remarkably enhanced enrichment probiotics Akkermansia Ligilactobacillus as well SCFA-producing bacteria (Eubacterium, Lactococcus, Coprococcus), while reducing abundance Eisenbergiella Rikenellaceae_RC9_gut_group. Also, notably up-regulated levels Claudin4, Occludin, ZO-1 proteins modulated argininosuccinic acid galactose. aforementioned findings suggest exerts significant anti-obesity effect by regulating abnormal microbiome, enhancing improving metabolic disorders.

Language: Английский

Inflammation and aging: signaling pathways and intervention therapies DOI Creative Commons
Xia Li, Chentao Li, Wanying Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 8, 2023

Abstract Aging is characterized by systemic chronic inflammation, which accompanied cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there an urgent need for a systematic organization inflammaging through dimensionality reduction. Factors secreted senescent cells, known as senescence-associated secretory phenotype (SASP), promote inflammation can induce senescence in normal cells. At same time, accelerates immune resulting weakened function inability to clear cells inflammatory factors, creates vicious cycle senescence. Persistently elevated levels organs such bone marrow, liver, lungs cannot be eliminated leading damage aging-related Therefore, has been recognized endogenous factor elimination could potential strategy anti-aging. Here we discuss at molecular, cellular, organ, disease levels, review current aging models, implications cutting-edge single cell technologies, well anti-aging strategies. Since preventing alleviating diseases improving overall quality life are ultimate goals research, our highlights critical features mechanisms along with latest developments future directions providing theoretical foundation novel practical

Language: Английский

Citations

474

Mouse models of sarcopenia: classification and evaluation DOI Creative Commons
Wenqing Xie, Miao He,

Dengjie Yu

et al.

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2021, Volume and Issue: 12(3), P. 538 - 554

Published: May 5, 2021

Sarcopenia is a progressive and widespread skeletal muscle disease that related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities death, its risk increases with age. With the deepening understanding sarcopenia, has become major clinical elderly key challenge healthy ageing. However, exact molecular mechanism this still unclear, selection treatment strategies evaluation effect are not same. Most importantly, early symptoms obvious easy ignore. In addition, manifestations each patient exactly same, which makes it difficult effectively study progression sarcopenia. Therefore, necessary develop use animal models understand pathophysiology sarcopenia therapeutic strategies. This paper reviews mouse can be used in including ageing models, genetically engineered hindlimb suspension chemical induction denervation immobilization models; analyses their advantages disadvantages application scope; finally summarizes models.

Language: Английский

Citations

148

Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid DOI Creative Commons
Junli Ma,

Zekun Liu,

Xinxin Gao

et al.

Pharmacological Research, Journal Year: 2023, Volume and Issue: 189, P. 106687 - 106687

Published: Feb. 4, 2023

Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying dysbiosis-related pathophysiological changes during aging remains largely unclear. In current study, we first performed remodeling on old mice by fecal transplantation (FMT) from young mice, and then characterized bacteria signature that was specifically altered FMT. Our results revealed FMT significantly improved natural systemic disorders, particularly exerted hepatoprotective effects, glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity intestinal barrier. Moreover, increased abundance of A.muciniphila, which almost nondetectable in mice. Interestingly, A.muciniphila supplementation also similar benefits with Notably, targeted metabolomics short chain fatty acids (SCFAs) only acetic acid consistently reversed Then, intervention beneficial actions both Caenorhabditis elegans conclusion, our study demonstrated disorders through its derived acid, suggesting interventions potent stimulative A. muciniphila growth production alternative effective way maintain healthy aging. The data RNAseq 16 S rRNA gene sequencing can be accessed NCBI accession number PRJNA848996 PRJNA849355.

Language: Английский

Citations

73

Galactose-Induced Skin Aging: The Role of Oxidative Stress DOI Creative Commons
Bauyrzhan Umbayev, Sholpan Askarova, Aigul Almabayeva

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 15

Published: June 17, 2020

Skin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable damaging skin's vital components through nonenzymatic glycation, covalent attachment sugar to protein, subsequent production advanced glycation end products (AGEs). This review is focused on role D-galactose in development skin its relation oxidative stress. The interest this problem was dictated by recent findings that used vitro vivo models. highlights advances underlying molecular mechanisms D-galactose-mediated cell senescence cytotoxicity. We have also proposed possible impact galactosemia clinical relevance. understanding mediated can help dermatologists optimize methods for prevention treatment aging-related diseases.

Language: Английский

Citations

80

The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders DOI Open Access
Joana F. Henriques, Diana Serra, Teresa C.P. Dinis

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8653 - 8653

Published: Nov. 17, 2020

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role the prevention treatment of different pathological conditions, which encouraged their consumption around world. exhibit significant neuroprotective role, mainly due to well-recognized antioxidant anti-inflammatory properties. Neuroinflammation is an intricate process relevant both homeostatic circumstances. Since progression several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered promising strategy those conditions. Recent data shown anti-neuroinflammatory abilities many anthocyanins metabolites onset development disorders. In this review, it will be discussed importance applicability these polyphenolic compounds as agents also scrutinized molecular mechanisms underlying modulation neuroinflammation by natural context diseases.

Language: Английский

Citations

70

Nrf2 a molecular therapeutic target for Astaxanthin DOI Creative Commons

Zeynab Kohandel,

Tahereh Farkhondeh, Michael Aschner

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 137, P. 111374 - 111374

Published: Feb. 18, 2021

Astaxanthin (ATX) is a red pigment carotenoid present in shrimp, salmon, crab, and asteroidean. Several studies have corroborated the anti-oxidant efficacy of ATX. In addition, ATX has anti-inflammatory, anti-apoptotic anti-proliferative properties. review, we discuss role Nrf2 mediating anti-cancer, anti-aging, neuroprotective, lung-protective, skin-protective, cardioprotective, hepatoprotective, anti-diabetic muscloprotective effects

Language: Английский

Citations

68

D-galactose-induced liver aging model: Its underlying mechanisms and potential therapeutic interventions DOI
Khairunnuur Fairuz Azman, Afifa Safdar, Rahimah Zakaria

et al.

Experimental Gerontology, Journal Year: 2021, Volume and Issue: 150, P. 111372 - 111372

Published: April 24, 2021

Language: Английский

Citations

66

Anti-aging effect of phlorizin on D-galactose–induced aging in mice through antioxidant and anti-inflammatory activity, prevention of apoptosis, and regulation of the gut microbiota DOI Creative Commons
Huiying Chen, Ling Dong, Xueyan Chen

et al.

Experimental Gerontology, Journal Year: 2022, Volume and Issue: 163, P. 111769 - 111769

Published: March 22, 2022

Aging is an inevitable and complicated process involving many physiological changes. Screening of natural biologically active anti-aging substances a current research hotspot. Phlorizin (PZ), important dihydrochalcone phytoconstituent, has been demonstrated to have antioxidant anti-tumor effects. In this paper, different doses PZ (20 40 mg/kg) were used the protective effect on D-galactose (D-gal)-induced aging mice. Following hematoxylin eosin staining by observing hippocampus, we found that alleviated damage caused D-gal in neuronal cells, while enhanced learning memory abilities mice radical eight-arm maze. order explain reasons for these effects, tested enzyme activity malonic dialdehyde concentration mouse serum, liver, brain tissue. The contents proteins related anti-inflammation apoptosis tissue analyzed, gut microbiota was also analyzed. results indicated improved significantly reducing content. Western blotting analysis suggested effectively neuro-apoptosis via regulating expressions Bax, Bcl-2, caspase-3. exerted effects interleukin-1β/inhibitor nuclear factor kappa B alpha/nuclear kappa-light-chain-enhancer activated B-cells signaling pathways tissues. Importantly, structure diversity microbiota, microbiota-gut-brain axis may hold key role PZ-induced conclusion, can be as potential drug candidate combat aging.

Language: Английский

Citations

52

Oxidation Stress as a Mechanism of Aging in Human Erythrocytes: Protective Effect of Quercetin DOI Open Access

Alessia Remigante,

Sara Spinelli,

Nancy Basile

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7781 - 7781

Published: July 14, 2022

Aging is a multi-factorial process developing through complex net of interactions between biological and cellular mechanisms it involves oxidative stress (OS) as well protein glycation. The aim the present work was to verify protective role Quercetin (Q), polyphenolic flavonoid compound, in d-Galactose (d-Gal)-induced model aging human erythrocytes. anion-exchange capability Band 3 (B3p) measured by rate constant SO42− uptake, thiobarbituric acid reactive substances (TBARS) levels—a marker lipid peroxidation—total sulfhydryl (-SH) groups, glycated hemoglobin (A1c), reduced glutathione/oxidized glutathione (GSH-GSSG) ratio were determined following exposure erythrocytes 100 mM d-Gal for 24 h, with or without pre-incubation 10 µM Q. results confirmed that activated OS pathways erythrocytes, affecting both membrane lipids proteins, denoted increased TBARS levels decreased total respectively. In addition, led an acceleration uptake B3p. Both alteration B3p function damage have been improved pre-treatment Q, which preferentially ameliorated peroxidation rather than oxidation. Moreover, Q prevented A1c formation, while no effect on endogenous antioxidant system observed. These findings suggest could be novel potential target treatments counteract aging-related disturbances. Further studies are needed confirm possible pharmacological strategies against aging.

Language: Английский

Citations

48

circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR DOI Creative Commons
Fengzhi Ding, Lin Lu, Chengjie Wu

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(17), P. 7550 - 7566

Published: Jan. 1, 2022

Rational: Senescence is a major aging process that contributes to the development of cardiovascular diseases, but underlying molecular mechanisms remain largely unknown.One reason due lack suitable animal models.We aimed generate cardiomyocyte (CM)-specific senescent model, uncover mechanisms, and develop new therapies for associated cardiac dysfunction. Methods:The gain/loss circHIPK3 approach was used explore role in (CM) senescence.To investigate function senescence, we generated CM-specific tamoxifen-induced knockout (CKO) mice.We also applied various analyses including PCR, Western blot, nuclear cytoplasmic protein extraction, immunofluorescence, echocardiography, RNA immunoprecipitation assay, RNA-pulldown co-immunoprecipitation.Results: Our novel CKO mice exhibited worse function, decreased expression telomere length shortening heart.The level senescence-inducer p21 hearts significantly increased survival poor compared with control mice.In vitro, CMs by overexpression, silencing.We showed scaffold mRNA-binding HuR E3 ubiquitin ligase β-TrCP.circHIPK3 silencing weakened interaction between β-TrCP, reduced ubiquitination, enhanced mRNA.Moreover, found injected human umbilical cord mesenchymal stem cell-derived exosomes (UMSC-Exos) levels, levels p21, longer length, good function.However, these beneficial effects exerted UMSC-Exos were inhibited circHIPK3.Conclusions: We successfully research.Our results deletion led exaggerated CM senescence function.As scaffold, binding β-TrCP cytoplasm, leading ubiquitination degradation activity.In addition, an anti-senescence cardio-protective effect delivering circHIPK3.These findings pave way

Language: Английский

Citations

44