FoxO3 and oxidative stress: a multifaceted role in cellular adaptation

Journal of Molecular Medicine, Год журнала: 2023, Номер 101(1-2), С. 83 - 99

Опубликована: Янв. 4, 2023

Язык: Английский

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SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 256, С. 114872 - 114872

Опубликована: Апрель 5, 2023

Manganese (Mn), as one of the environmental risk factors for Parkinson's disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible causative issue Mn neurotoxicity, molecular mechanism parkinsonism caused by not explored clearly. The results in vivo vitro experiments showed that overexposure to impairment dysfunction, accompanied increase IL-1β, IL-6, TNF-α mRNA expression, nerve cell apoptosis, microglia activation, NF-κB poor neurobehavior performance. This is due Mn-induced downregulation SIRT1. Upregulation SIRT1 could alleviate neuroinflammation, yet these beneficial effects were abolished following 3-MA administration. Furthermore, we found interfered with acetylation FOXO3 BV2 cells, leading a decrease nuclear translocation FOXO3, its binding LC3B promoter transcription activity. be antagonized upregulation Finally, it proved SIRT1/FOXO3-LC3B signaling involves impairment.

Язык: Английский

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Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Янв. 23, 2024

Abstract Background CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, persistently high level of promotes longevity and ameliorates an age-related skin phenotype transgenic mice. Here we translate the genetic evidence into pharmaceutical application using potent activator, hesperetin, which enhances expression HEK001 human keratinocytes from older person. We also treated naturally aged mice order to study activator’s anti-aging efficacy. Methods studied biological effects hesperetin on aging using, firstly, cell-based platform, namely keratinocyte cell line established Secondly, used mouse model, old at 21-month old. In latter case, investigate efficacy ultraviolet B (UVB)-induced photoaging skin. identify underlying mechanisms potential pathways involved this process carried out transcriptomic analysis. Finally, knockdown Cisd2 knockout were Cisd2-dependent Results Four findings are pinpointed. Firstly , skin, mainly expressed proliferating epidermal basal layer and, furthermore, sun-exposed epidermis. Secondly person, mitochondrial function protects against reactive oxygen species-induced oxidative stress via increased expression; enhancement CISD2-dependent. Additionally, alleviates UVB-induced damage suppresses matrix metalloproteinase-1 expression, being major indicator keratinocytes. Thirdly analysis revealed that modulates panel differentially genes associated with function, redox homeostasis, inflammation attenuate senescence. Intriguingly, activates two known longevity-associated regulators, FOXO3a FOXM1, suppress senescence-associated secretory phenotype. Finally ameliorate occurs mechanism involving CISD2. Most strikingly, late-life treatment started lasting for 5 months, able retard rejuvenate Conclusions Our results reveal pharmacological elevation stage feasible approach effectively mitigating both intrinsic extrinsic could act as functional food or skincare product fighting

Язык: Английский

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Dietary Polyphenols as Geroprotective Compounds: From Blue Zones to Hallmarks of Ageing

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102733 - 102733

Опубликована: Март 1, 2025

Язык: Английский

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Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols

Advances in Nutrition, Год журнала: 2023, Номер 14(5), С. 1111 - 1130

Опубликована: Июнь 2, 2023

Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as cellular defense mechanism from acquiring potentially harmful genetic faults. However, recent studies highlight that senescent might also alter the local tissue environment and concur chronic inflammation cancer risk by secreting inflammatory matrix remodeling factors, senescence-associated secretory phenotype (SASP). Indeed, during aging age-related diseases, amass mammalian tissues, likely contributing inevitable loss function we age. thus become one potential target tackle age-associated diseases well development. One important aspect characterizing is their telomere length. Telomeres shorten consequence multiple replications, gradually leading arrest, known replicative senescence. Interestingly, large majority cells, escape strategy length maintained telomerase, favoring initiation tumor survival. There growing evidence showing how (poly)phenols can impact maintenance through molecular mechanisms depending on dose phenotypes. Although normally, maintain support telomerase activity, this activity negatively modulated, accelerating attrition promoting death. Some have shown exert senolytic suggesting both antiaging (directly eliminating cells) anticancer (indirectly, via SASP inhibition) potentials. In review, analyze selective (poly)phenol discriminate between vitro vivo human applications considering bioavailability, influence gut microbiota, dose-response effects.

Язык: Английский

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Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Food Frontiers, Год журнала: 2024, Номер 5(2), С. 267 - 310

Опубликована: Янв. 10, 2024

Abstract The revolution in aging research through the past decade has driven progress interventions that promote longevity. Dissection of “old” hallmarks provided solid data for definition at least three “new” ones, opening avenues development novel hallmark‐targeted pro‐longevity approaches. quest geroprotectors is enormous interest with ultimate goal finding alchemical stone induces healthy and increases lifespan, pushing limits human longevity or even uncovering absence such limits. Several well‐appreciated are recognized as promoters natural origin metformin, resveratrol, aspirin, spermidine. As search pharmacological modulators healthspan lifespan continues, numerous studies focusing on potential plant secondary metabolites. current review attempts to critically assess available breakthrough discoveries field over decade. Correspondingly, approaches targeting have been outlined, future goals enlightened. Special emphasis placed plant‐derived compounds agents.

Язык: Английский

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Potent FOXO3a Activators from Biologically Active Compound Library for Cancer Therapeutics: An in silico Approach

Applied Biochemistry and Biotechnology, Год журнала: 2023, Номер 195(8), С. 4995 - 5018

Опубликована: Апрель 5, 2023

Язык: Английский

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circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood–brain barrier integrity and cognitive function in uremic encephalopathy

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Апрель 17, 2024

Abstract Uremic encephalopathy (UE) poses a significant challenge in neurology, leading to the need investigate involvement of non-coding RNA (ncRNA) its development. This study employed ncRNA-seq and RNA-seq approaches identify fundamental ncRNAs, specifically circRNA miRNA, pathogenesis UE using mouse model. In vitro vivo experiments were conducted explore circRNA-PTPN4/miR-301a-3p/FOXO3 axis effects on blood–brain barrier (BBB) function cognitive abilities. The research revealed that circRNA-PTPN4 binds inhibits miR-301a-3p, an increase FOXO3 expression. upregulation results alterations transcriptional regulation ZO-1, affecting permeability human brain microvascular endothelial cells (HBMECs). also influences growth, proliferation, migration HBMECs. Mice with exhibited deficits, which reversed by overexpression circRNA-PTPN4, whereas silencing exacerbated these deficits. Furthermore, uremic mice showed neuronal loss, inflammation, dysfunction BBB, expression demonstrating therapeutic effects. conclusion, plays role promoting sequestering ultimately ZO-1 restoration BBB UE. process contributes Graphical 1. is identified as key regulator integrity encephalopathy. 2. sequestration miR-301a-3p enhances expression, improved permeability. 3. Overexpression restores abilities reduces loss inflammatory infiltration.

Язык: Английский

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20(S)-ginsenoside Rg3 protects against diabetic muscle atrophy by promoting myoblastic differentiation and protecting mitochondrial function

Phytomedicine, Год журнала: 2024, Номер 134, С. 155964 - 155964

Опубликована: Авг. 15, 2024

Язык: Английский

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Epigenetic factors and inflammaging: FOXO3A as a potential biomarker of sarcopenia and upregulation of DNMT3A and SIRT3 in older adults

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 17, 2025

Background Epigenetic factors influence inflammaging and geriatric disorders such as sarcopenia frailty. It is necessary to develop a biomarker/panel of biomarkers for fast easy diagnostics. Currently, hard-to-access equipment required diagnose sarcopenia. The development will prevent many older adults from being excluded the diagnostic process. Methods In this study, we analyzed selected gene expression profiles, namely, SIRT1 , SIRT3 SIRT6 DNMT3A FOXO1 FOXO3A ELAVL1 in whole blood. study included 168 subjects divided into five groups: patients hospitalized at Geriatrics Clinic Polyclinic with sarcopenia, frailty syndrome, or without those (geriatric control), non-hospitalized healthy controls (HC) aged 25 30 years over 50 years. Results We revealed lower mRNA level (p<0.001) sarcopenic compared controls. Furthermore, detected upregulation (p=0.003) (p=0.015) HC old Interestingly, observed 2 cluster formations during correlation analysis ( ). also noted correlations clinical parameters levels group, vitamin D (r=0.64, p=0.010), creatine kinase (r=–0.58, p=0.032) (r=–0.59, p=0.026), creatinine (r=0.57, erythrocyte sedimentation rate (ESR) (r=0.69, p=0.004), lactate dehydrogenase (LDH) (r=–0.86, p=0.007). syndrome appendicular skeletal muscle mass (ASMM) (r=0.59, p=0.026) level. controls, serum iron (r=–0.79, p=0.036). Conclusions Our potential biomarker high epigenetic ) adults.

Язык: Английский

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