Calorie restriction and life-extending mutation downregulate miR-34a to facilitate lipid metabolism in the liver

Experimental Gerontology, Год журнала: 2024, Номер 194, С. 112506 - 112506

Опубликована: Июль 10, 2024

Ames dwarf mice (df/df) display delayed aging relative to their normal (N) siblings, living approximately 40-60 % longer. As such, investigating the mechanisms that enable these organisms have extended lifespan is useful for development of interventions slow and deter age-related disease. Nonalcoholic fatty liver disease (NAFLD) a condition characterized by accumulation excess adipose tissue in liver. Previous studies highlight potential calorie restriction (CR) promoting longevity, but little known about its effects on biomolecular processes govern NAFLD. In this study, we examined role 6-month CR genes regulating lipid metabolism livers long-living df/df N littermates. Importantly, our findings showed significant downregulation miR-34a-5p N-CR regardless dietary regimen. Alongside, RT-PCR results indicated correlated with expression metabolism-associated mRNAs involved modulating de novo lipogenesis (DNL), acid oxidation (FAO), very-low density lipoprotein transport (VLDL-T), reverse cholesterol (RCT). To further verify metabolic processes, transfected human cancer (HepG2) cell line miR-34a mimic, studied effect direct targets Sirt1, Ampk, Ppara as well downstream genes. Our suggest life extending mutation are robust drivers signaling pathway prevent pathogenesis diseases improving overall homeostasis.

Язык: Английский

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Hippocampal microRNA-181a overexpression participates in anxiety and ethanol related behaviors via regulating the expression of SIRT-1

Physiology & Behavior, Год журнала: 2025, Номер unknown, С. 114839 - 114839

Опубликована: Фев. 1, 2025

Язык: Английский

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MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute loss, but high treatment burden and efficacy with chronic therapy highlight need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as key regulator aging age-related diseases, its role neovascular AMD unclear. In an injury-induced murine CNV model, we discovered miR-34a promoted pathological angiogenesis, without altering expression Vegfa or receptor Kdr, canonical regulators CNV. Mechanistically, directly targets inhibits transcription KLF2 thereby upregulating pro-angiogenic factors CXCR4 CXCL12. Finally, show exacerbates aged mice expressed lesions excised from wet patients. These findings establish causal link between AMD. Identification molecular mechanism involved pathogenesis prevalent debilitating ocular disease.

Язык: Английский

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MicroRNA‐34a Mediates the Aldosterone‐Induced Acceleration of Endothelial Senescence

International Journal of Hypertension, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Inappropriate aldosterone production relative to sodium status is known induce arterial hypertension and cause detrimental effects on endothelium vascular remodeling. This study investigated whether microRNAs (miRs) serve as key mediators of aldosterone's endothelial dysfunction. Using human umbilical vein cells (HUVECs) a model system, we demonstrated that treatment suppressed cellular proliferation migration while promoting senescence. Mechanistically, observed exposure significantly upregulated miR-34a expression in HUVECs. The functional significance was confirmed when specific inhibitors reversed antiproliferative prosenescence effects. To elucidate the underlying molecular pathway, performed comprehensive biological analyses, which revealed target genes were predominantly associated with Notch signaling pathway. Western blot analysis further validated promotes senescence HUVECs through negative regulation NOTCH1. Collectively, our findings identify crucial mediator aldosterone-induced cell via NOTCH1 suggesting its potential therapeutic for aldosterone-related diseases.

Язык: Английский

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Endothelial miR-34a deletion guards against aneurysm development despite endothelial dysfunction

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167812 - 167812

Опубликована: Март 1, 2025

Язык: Английский

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