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Abstract

An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between transcriptome and proteome at soma and synaptic level during aging. Proteomic and transcriptomic data analysis reveal that, in young animals, proteins and transcripts are correlated and synaptic regulation is driven by changes in the soma. During aging, there is a decoupling between transcripts and proteins and between somatic and synaptic compartments. Furthermore, soma-synapse gradient of ribosomal genes changes upon aging, i.e. ribosomal transcripts are less abundant and ribosomal proteins are more abundant in synaptic compartment of old mice with respect to younglings. Additionally, transcriptomics data highlight a difference in the splicing of certain synaptic mRNA with aging. Taken together, our data provide a valuable resource for the study of the aging synapse.

Competing Interest Statement

The authors have declared no competing interest.

Details

1009240
Title
The Aging Synapse: An Integrated Proteomic And Transcriptomic Analysis
Publication title
bioRxiv; Cold Spring Harbor
Publication year
2024
Publication date
Dec 20, 2024
Section
New Results
Publisher
Cold Spring Harbor Laboratory Press
Source
BioRxiv
Place of publication
Cold Spring Harbor
Country of publication
United States
University/institution
Cold Spring Harbor Laboratory Press
Publication subject
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
Document type
Working Paper
ProQuest document ID
3147576530
Document URL
https://www.proquest.com/working-papers/aging-synapse-integrated-proteomic-transcriptomic/docview/3147576530/se-2?accountid=208611
Copyright
© 2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Last updated
2024-12-21
Database
ProQuest One Academic