Dataset Information

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

ABSTRACT: Polyamines have been shown to delay cellular and organismal aging and to provide cardiovascular protection in humans. Because age-related cardiovascular dysfunction is often accompanied by impaired mitochondrial biogenesis and function, we explored the ability of spermidine (SPD), a major mammalian polyamine, to attenuate cardiac aging through activation of mitochondrial biogenesis. Cardiac polyamine levels were reduced in aged (24-month-old) rats. Six-week SPD supplementation restored cardiac polyamine content, preserved myocardial ultrastructure, and inhibited mitochondrial dysfunction. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated, respectively, in the myocardium of older rats. These changes were paralleled by age-dependent downregulation of components of the sirtuin-1/peroxisome proliferator-activated receptor gamma coactivator alpha (SIRT1/PGC-1?) signaling pathway, an important regulator of mitochondrial biogenesis. SPD administration increased SIRT1, PGC-1?, nuclear respiratory factors 1 and 2 (NRF1, NRF2), and mitochondrial transcription factor A (TFAM) expression; decreased ROS production; and improved OXPHOS performance in senescent (H₂O₂-treated) cardiomyocytes. Inhibition of polyamine biosynthesis or SIRT1 activity abolished these effects. PGC-1? knockdown experiments confirmed that SPD activated mitochondrial biogenesis through SIRT1-mediated deacetylation of PGC-1?. These data provide new insight into the antiaging effects of SPD, and suggest potential applicability to protect against deterioration of cardiac function with aging.

SUBMITTER: Wang J

PROVIDER: S-EPMC6977682 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

Wang Junying J Li Shaoqi S Wang Ju J Wu Feixiang F Chen Yuhan Y Zhang Hao H Guo Yubo Y Lin Yan Y Li Lingxu L Yu Xue X Liu Ting T Zhao Yajun Y

Aging 20200106 1

Polyamines have been shown to delay cellular and organismal aging and to provide cardiovascular protection in humans. Because age-related cardiovascular dysfunction is often accompanied by impaired mitochondrial biogenesis and function, we explored the ability of spermidine (SPD), a major mammalian polyamine, to attenuate cardiac aging through activation of mitochondrial biogenesis. Cardiac polyamine levels were reduced in aged (24-month-old) rats. Six-week SPD supplementation restored cardiac p ...[more]

PMID: 31907336

Similar Datasets

Project description:Purpose:RNA-Seq analysis was performed on mouse hearts with or without hispidulin treatment 4 weeks after arotic banding or sham surgery to determining the effect of hispidulin on pressure overload induced cardiac hypertrophy. Methods: the mRNA profiles of mouse hearts underwent sham or arotic banding surgery with treatment of hispidulin or DMSO were generated by RNA-seq analysis in triplicate. The expression level of gene was calculated by RSEM(v.1.2.12). Differential expression analysis was performed using the DESeq2(V 1.4.5). Results: RNA isolation, library construction, and sequencing were performed on a BGISEQ-500 (Beijing Genomic Institution, www.genomics.org.cn, BGI). For the gene expression analysis, the fold changes were also estimated according to the fragments per kilobase of exon per million fragments mapped (FPKM) in each sample. The significance of different gene expression was defined by the following filter criteria: false discovery rate (FDR) ≤0.001 and log2-ratio 1. After comparing of DMSO+AB group and hispidulin+AB group, we found that 113 genes were significantly differentially expressed. Gene ontology and cluster analysis indicated that alternated genes were enriched in fatty acid oxidation, glucose metabolism, TCA cycle, oxidative phosphorylation, hypertrophic cardiomyopathy, ECM organism, oxidative stress and unfolded protein binding. This result indicated that hispidulin improved mitochondrial function. Conclusions: Our study represents the first detailed analysis of heart transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

Dataset Information

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

Publications

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure