Dataset Information

Decoupling of mRNA and protein expression in aging brains reveals the age-dependent adaptation of specific gene subsets

ABSTRACT: During aging, changes in gene expression are associated with decline in physical and cognitive abilities. Here, we investigated the connection between changes of mRNA and protein expression in the brain by comparing the transcriptome and proteome of the mouse cortex during aging. Our transcriptomic analysis revealed that aging mainly triggers gene activation in the cortex. We showed that increase of mRNA expression correlates with protein expression, specifically in the anterior cingulate cortex where we also observed an increase of cortical thickness during aging. Genes exhibiting an aging-dependent increase of mRNA and protein levels are involved in sensory perception and immune functions. Our proteomic analysis also identified changes in protein abundance in the aging cortex and highlighted a subset of proteins that were differentially enriched but exhibited stable mRNA levels during aging, implying the contribution of aging-related post transcriptional and post-translational mechanisms. These specific genes were associated with general biological processes such as translation, ribosome assembly and protein degradation, but also important brain functions related to neuroplasticity. By decoupling mRNA and protein expression, we have thus characterized distinct subsets of genes that differentially adjust to cellular aging in the cerebral cortex.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Benoit Laurent

LAB HEAD: Benoit Laurent

PROVIDER: PXD038179 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets.

Khatir Inès I Brunet Marie A MA Meller Anna A Amiot Florent F Patel Tushar T Lapointe Xavier X Avila Lopez Jessica J Guilloy Noé N Castonguay Anne A Husain Mohammed Amir MA Germain Joannie St JS Boisvert François-Michel FM Plourde Mélanie M Roucou Xavier X Laurent Benoit B

Cells 20230214 4

During aging, changes in gene expression are associated with a decline in physical and cognitive abilities. Here, we investigate the connection between changes in mRNA and protein expression in the brain by comparing the transcriptome and proteome of the mouse cortex during aging. Our transcriptomic analysis revealed that aging mainly triggers gene activation in the cortex. We showed that an increase in mRNA expression correlates with protein expression, specifically in the anterior cingulate co ...[more]

PMID: 36831282

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Project description:Age-related methylation changes have been identified in various tissues and organisms, yet the underlying DNA methylation alterations in muscle aging process have not been clearly clarified. Whilst, many studies revealed that the structural and functional changes in skeletal muscle during aging process started from the mid-point of lifespan. In this study, we used pigs aged 0.5 year and 7 years, representing young and middle-aged periods. Using methylated DNA immunoprecipitation sequencing, we performed comprehensive genome-wide DNA methylation profiling for longissimus dorsi muscle in young and middle-aged pigs. We found more genes showed differently methylated in genebody. In details, 185 human ortholog genes contained DMRs that located in the promoter region, while 657 genes and 1063 genes with DMRs in gene body showed hypermethylation and hypomethylation in MA pigs, respectively. From the gene enrichment analysis, genebody hypermethylated genes showed significant enrichment for several molecular functions such as M-bM-^@M-^XGTPase regulator activityM-bM-^@M-^Y, M-bM-^@M-^XATP bindingM-bM-^@M-^Y and M-bM-^@M-^Xprotein kinase activityM-bM-^@M-^Y. Notably, genebody hypomethylated genes showed significant enrichment for various proteolysis and protein catabolic process. However, genes with DMR in their promoter region were not significantly enriched in any biology process. Proteolysis-associated genes, such as FOXO3 and FGFR1, showed different genebody methylation and mRNA expression level in two age groups, which may contribute to muscle atrophy during aging. Especially, other tumorigenesis-associated genes including GPI and GRB2, exhibited increasing mRNA level in middle-aged pigs, suggesting the possible higher risk of having cancer in human middle-aged period. Our results will serve as a valuable resource in aging studies, promote pig as a model organism for human aging research and accelerate the considerable 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 and the genome-wide gene expression profile between the two age periods. This submission represents transcriptome component of study.

Dataset Information

Decoupling of mRNA and protein expression in aging brains reveals the age-dependent adaptation of specific gene subsets

Publications

Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets.

Similar Datasets

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