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

Autor: Ashiqueali SA; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA., Zhu X; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA., Wiesenborn DS; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA; Department of Biotechnology, University of Applied Sciences Kaiserslautern, Zweibrücken, Germany., Gesing A; Department of Endocrinology of Ageing, Medical University of Lodz, Poland., Schneider A; Department of Nutrition, Universidade Federal de Pelotas, Pelotas, RS, Brazil., Noureddine SA; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA., Correa-Garcia CG; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA; Department of Medicine, San Juan Bautista School of Medicine, Caguas, Puerto Rico., Masternak MM; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA; Department of Head and Neck Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland., Siddiqi SA; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA. Electronic address: shadab.siddiqi@ucf.edu.
Jazyk: angličtina
Zdroj: Experimental gerontology [Exp Gerontol] 2024 Sep; Vol. 194, pp. 112506. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1016/j.exger.2024.112506
Abstrakt: 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 to have extended lifespan is useful for the development of interventions to slow aging and deter age-related disease. Nonalcoholic fatty liver disease (NAFLD) is a condition that is characterized by the accumulation of excess adipose tissue in the liver. Previous studies highlight the potential of calorie restriction (CR) in promoting longevity, but little is known about its effects on the biomolecular processes that govern NAFLD. In this study, we examined the role of 6-month CR on genes regulating lipid metabolism in the livers of long-living df/df mice and their N littermates. Importantly, our findings showed significant downregulation of miR-34a-5p in N-CR mice and df/df mice regardless of dietary regimen. Alongside, our RT-PCR results indicated that downregulation of miR-34a-5p is correlated with the expression of metabolism-associated mRNAs involved in modulating the processes of de novo lipogenesis (DNL), fatty acid oxidation (FAO), very-low density lipoprotein transport (VLDL-T), and reverse cholesterol transport (RCT). To further verify the role of miR-34a-5p in regulating metabolic processes, we transfected the human liver cancer (HepG2) cell line with miR-34a mimic, and studied its effect on direct targets Sirt1, Ampk, and Ppara as well as downstream lipid transport regulating genes. Our findings suggest that CR and df/df life extending mutation are robust drivers of the miR-34a-5p signaling pathway and prevent the pathogenesis of age-related diseases by improving overall lipid homeostasis.
Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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