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

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge, Ma : Cell Press
      Original Publication: Cambridge, MIT Press.
    • Subject Terms:
      Caenorhabditis elegans*/genetics ; Caenorhabditis elegans*/physiology ; Aging*/genetics ; Gene Regulatory Networks* ; Transcriptome*/genetics ; Longevity*/genetics; Animals ; Caenorhabditis elegans Proteins/metabolism ; Caenorhabditis elegans Proteins/genetics ; RNA, Messenger/metabolism ; RNA, Messenger/genetics
    • 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.
      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.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Caenorhabditis elegans; aging; complex systems; computational biology; gene regulation; individual variation; non-genetic individuality; quantitative biology; statistical modeling
    • Accession Number:
      0 (Caenorhabditis elegans Proteins)
      0 (RNA, Messenger)
    • Publication Date:
      Date Created: 20240622 Date Completed: 20240727 Latest Revision: 20240727
    • Publication Date:
      20240729
    • Accession Number:
      10.1016/j.cell.2024.05.050
    • Accession Number:
      38908368