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PLoS Comput Biol. 2019 Jul 3;15(7):e1007162. doi: 10.1371/journal.pcbi.1007162. eCollection 2019 Jul.

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

Author information

1
Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland.
2
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Laboratory of Integrative Systems Physiology, EPFL, Lausanne, Switzerland.
4
University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

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