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Comprehensive transcriptome analysis of skeletal muscle in the NADS knockout mice.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD+) is a pivotal molecule involved in various biological processes, including energy production, protein post-translational modification, DNA repair, calcium mobilization, and 5’-capping of mRNA. Accumulating evidence has revealed that NAD+ declines with age by disturbing the balance between its synthesis and degradation. Decreased NAD+ levels result in deterioration of physiological functions in multiple tissues, including the liver, muscle, kidney, and brain. Contrarily, the repletion of NAD+ levels by supplementation of NAD+ precursors have beneficial effects on lifespan, physiological aging, and aging-associated diseases. However, it is unknown whether declined NAD+ levels in young age affect aging processes. Therefore, in this study, to better understand the effect of NAD+ levels on the aging processes, we performed the RNA-sequencing using skeletal muscle samples from young and old wild-type and NAD synthetase (NADS)-deficient mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE274297 | GEO | 2025/12/16

REPOSITORIES: GEO

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Project description:Background: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. Results: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. Conclusions: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference between the two age periods.

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Comprehensive transcriptome analysis of skeletal muscle in the NADS knockout mice.

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