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

TitreCross-species functional modules link proteostasis to human normal aging.
Publication TypeJournal Article
Year of Publication2019
AuthorsKomljenovic, A, Li, H, Sorrentino, V, Kutalik, Z, Auwerx, J, Robinson-Rechavi, M
JournalPLOS Computational Biology
Volume15
Issue7
Paginatione1007162
Date Published07/2019
DOI10.1371/journal.pcbi.1007162
ISSN1553-7358
Mots-clésBehavior and Systematics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Ecology, Evolution, genetics, Modelling and Simulation, Molecular Biology
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.

Alternate URL

https://www.ncbi.nlm.nih.gov/pubmed/31269015?dopt=Abstract

Alternate JournalPLoS Comput. Biol.
Citation Key / SERVAL ID9637
Peer reviewRefereed
PubMed ID31269015

                         

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