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

Author:

Khatir Inès12,Brunet Marie A.34ORCID,Meller Anna5ORCID,Amiot Florent12,Patel Tushar12,Lapointe Xavier34,Avila Lopez Jessica12ORCID,Guilloy Noé2,Castonguay Anne2,Husain Mohammed Amir16,Germain Joannie St.12,Boisvert François-Michel45,Plourde Mélanie16,Roucou Xavier247ORCID,Laurent Benoit12ORCID

Affiliation:

1. Research Center on Aging, Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie-Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC J1H 4C4, Canada

2. Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada

3. Department of Pediatrics, Medical Genetics Service, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada

4. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Sherbrooke, QC J1H 5N4, Canada

5. Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Québec, QC J1H 5N4, Canada

6. Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada

7. Quebec Network for Research on Protein Function, Structure, and Engineering, PROTEO, Québec, QC G1V 0A6, Canada

Abstract

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 cortex, where we also observed an increase in 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, and 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.

Funder

Canadian Institutes of Health Research

Faculty of Medicine and Health Sciences at the Université de Sherbrooke

Fonds de Recherche du Québec-Santé

Publisher

MDPI AG

Subject

General Medicine

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