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Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart
Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104701/ https://www.ncbi.nlm.nih.gov/pubmed/35277432 http://dx.doi.org/10.1101/gr.275672.121 |
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author | Gerdes Gyuricza, Isabela Chick, Joel M. Keele, Gregory R. Deighan, Andrew G. Munger, Steven C. Korstanje, Ron Gygi, Steven P. Churchill, Gary A. |
author_facet | Gerdes Gyuricza, Isabela Chick, Joel M. Keele, Gregory R. Deighan, Andrew G. Munger, Steven C. Korstanje, Ron Gygi, Steven P. Churchill, Gary A. |
author_sort | Gerdes Gyuricza, Isabela |
collection | PubMed |
description | Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process. |
format | Online Article Text |
id | pubmed-9104701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91047012022-06-04 Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart Gerdes Gyuricza, Isabela Chick, Joel M. Keele, Gregory R. Deighan, Andrew G. Munger, Steven C. Korstanje, Ron Gygi, Steven P. Churchill, Gary A. Genome Res Research Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process. Cold Spring Harbor Laboratory Press 2022-05 /pmc/articles/PMC9104701/ /pubmed/35277432 http://dx.doi.org/10.1101/gr.275672.121 Text en © 2022 Gerdes Gyuricza et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by/4.0/This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Gerdes Gyuricza, Isabela Chick, Joel M. Keele, Gregory R. Deighan, Andrew G. Munger, Steven C. Korstanje, Ron Gygi, Steven P. Churchill, Gary A. Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title | Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title_full | Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title_fullStr | Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title_full_unstemmed | Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title_short | Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
title_sort | genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104701/ https://www.ncbi.nlm.nih.gov/pubmed/35277432 http://dx.doi.org/10.1101/gr.275672.121 |
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