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Article

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

by
Inès Khatir
1,2,†,
Marie A. Brunet
3,4,†,
Anna Meller
5,†,
Florent Amiot
1,2,
Tushar Patel
1,2,
Xavier Lapointe
3,4,
Jessica Avila Lopez
1,2,
Noé Guilloy
2,
Anne Castonguay
2,
Mohammed Amir Husain
1,6,
Joannie St. Germain
1,2,
François-Michel Boisvert
4,5,
Mélanie Plourde
1,6,
Xavier Roucou
2,4,7 and
Benoit Laurent
1,2,*
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
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2023, 12(4), 615; https://doi.org/10.3390/cells12040615
Submission received: 26 January 2023 / Revised: 7 February 2023 / Accepted: 12 February 2023 / Published: 14 February 2023
(This article belongs to the Special Issue Protein Biology of the Aging Process)
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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.
Keywords: aging; brain; cortex; mRNA; transcriptome; protein; proteome aging; brain; cortex; mRNA; transcriptome; protein; proteome

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MDPI and ACS Style

Khatir, I.; Brunet, M.A.; Meller, A.; Amiot, F.; Patel, T.; Lapointe, X.; Avila Lopez, J.; Guilloy, N.; Castonguay, A.; Husain, M.A.; et al. Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets. Cells 2023, 12, 615. https://doi.org/10.3390/cells12040615

AMA Style

Khatir I, Brunet MA, Meller A, Amiot F, Patel T, Lapointe X, Avila Lopez J, Guilloy N, Castonguay A, Husain MA, et al. Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets. Cells. 2023; 12(4):615. https://doi.org/10.3390/cells12040615

Chicago/Turabian Style

Khatir, Inès, Marie A. Brunet, Anna Meller, Florent Amiot, Tushar Patel, Xavier Lapointe, Jessica Avila Lopez, Noé Guilloy, Anne Castonguay, Mohammed Amir Husain, and et al. 2023. "Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets" Cells 12, no. 4: 615. https://doi.org/10.3390/cells12040615

APA Style

Khatir, I., Brunet, M. A., Meller, A., Amiot, F., Patel, T., Lapointe, X., Avila Lopez, J., Guilloy, N., Castonguay, A., Husain, M. A., Germain, J. S., Boisvert, F.-M., Plourde, M., Roucou, X., & Laurent, B. (2023). Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets. Cells, 12(4), 615. https://doi.org/10.3390/cells12040615

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