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Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony.

Authors :
Eder M
Martin OMF
Oswal N
Sedlackova L
Moutinho C
Del Carmen-Fabregat A
Menendez Bravo S
Sebé-Pedrós A
Heyn H
Stroustrup N
Source :
Cell [Cell] 2024 Jul 25; Vol. 187 (15), pp. 3919-3935.e19. Date of Electronic Publication: 2024 Jun 21.
Publication Year :
2024

Abstract

In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed. Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans "pan-transcriptome"-a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging.<br />Competing Interests: Declaration of interests H.H. is co-founder of Omniscope and scientific advisory board member of MiRXES. C.M. is scientific consultant member of GLG.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4172
Volume :
187
Issue :
15
Database :
MEDLINE
Journal :
Cell
Publication Type :
Academic Journal
Accession number :
38908368
Full Text :
https://doi.org/10.1016/j.cell.2024.05.050