Cross-species functional modules link proteostasis to human normal aging.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_DB3E6C72F674
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cross-species functional modules link proteostasis to human normal aging.
Journal
PLoS computational biology
Author(s)
Komljenovic A., Li H., Sorrentino V., Kutalik Z., Auwerx J., Robinson-Rechavi M.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
15
Number
7
Pages
e1007162
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
The evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan, such as caloric restriction, suggests that aging-related research in model organisms is directly relevant to human aging. Since human lifespan is a complex trait, a systems-level approach will contribute to a more comprehensive understanding of the underlying aging landscape. Here, we integrate evolutionary and functional information of normal aging across human and model organisms at three levels: gene-level, process-level, and network-level. We identify evolutionarily conserved modules of normal aging across diverse taxa, and notably show proteostasis to be conserved in normal aging. Additionally, we find that mechanisms related to protein quality control network are enriched for genes harboring genetic variants associated with 22 age-related human traits and associated to caloric restriction. These results demonstrate that a systems-level approach, combined with evolutionary conservation, allows the detection of candidate aging genes and pathways relevant to human normal aging.
Keywords
Adult, Aged, Aging/genetics, Aging/metabolism, Animals, Caenorhabditis elegans, Caloric Restriction, Computational Biology, Drosophila melanogaster, Evolution, Molecular, Female, Gene Expression Profiling, Genetic Markers, Humans, Longevity/genetics, Longevity/physiology, Male, Mice, Middle Aged, Models, Biological, Proteostasis/genetics, Species Specificity, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
04/07/2019 12:10
Last modification date
30/04/2021 6:15
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