A hierarchical process model links behavioral aging and lifespan in C. elegans

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  • dc.contributor.author Oswal, Natasha
  • dc.contributor.author Martin, Olivier M. F.
  • dc.contributor.author Stroustrup, Sofia
  • dc.contributor.author Bruckner, Monika Anna Matusiak
  • dc.contributor.author Stroustrup, Nicholas
  • dc.date.accessioned 2023-01-19T06:56:35Z
  • dc.date.available 2023-01-19T06:56:35Z
  • dc.date.issued 2022
  • dc.description.abstract Aging involves a transition from youthful vigor to geriatric infirmity and death. Individuals who remain vigorous longer tend to live longer, and within isogenic populations of C. elegans the timing of age-associated vigorous movement cessation (VMC) is highly correlated with lifespan. Yet, many mutations and interventions in aging alter the proportion of lifespan spent moving vigorously, appearing to "uncouple" youthful vigor from lifespan. To clarify the relationship between vigorous movement cessation, death, and the physical declines that determine their timing, we developed a new version of the imaging platform called "The Lifespan Machine". This technology allows us to compare behavioral aging and lifespan at an unprecedented scale. We find that behavioral aging involves a time-dependent increase in the risk of VMC, reminiscent of the risk of death. Furthermore, we find that VMC times are inversely correlated with remaining lifespan across a wide range of genotypes and environmental conditions. Measuring and modelling a variety of lifespan-altering interventions including a new RNA-polymerase II auxin-inducible degron system, we find that vigorous movement and lifespan are best described as emerging from the interplay between at least two distinct physical declines whose rates co-vary between individuals. In this way, we highlight a crucial limitation of predictors of lifespan like VMC-in organisms experiencing multiple, distinct, age-associated physical declines, correlations between mid-life biomarkers and late-life outcomes can arise from the contextual influence of confounding factors rather than a reporting by the biomarker of a robustly predictive biological age.
  • dc.description.sponsorship This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 852201), the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), the CERCA Programme/Generalitat de Catalunya, the MEIC Excelencia award BFU2017-88615-P, and an award from the Glenn Foundation for Medical Research to NS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Oswal N, Martin OMF, Stroustrup S, Bruckner MAM, Stroustrup N. A hierarchical process model links behavioral aging and lifespan in C. elegans. PLoS Comput Biol. 2022 Sep 30;18(9):e1010415. DOI: 10.1371/journal.pcbi.1010415
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1010415
  • dc.identifier.issn 1553-734X
  • dc.identifier.uri http://hdl.handle.net/10230/55335
  • dc.language.iso eng
  • dc.publisher Public Library of Science (PLoS)
  • dc.relation.ispartof PLoS Comput Biol. 2022 Sep 30;18(9):e1010415
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/852201
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88615-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88615-P
  • dc.rights © 2022 Oswal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Aging
  • dc.subject.keyword Biomarkers
  • dc.subject.keyword Caenorhabditis elegans
  • dc.subject.keyword Linear regression analysis
  • dc.subject.keyword Markov processes
  • dc.subject.keyword Random walk
  • dc.subject.keyword RNA polymerase
  • dc.subject.keyword Regression analysis
  • dc.title A hierarchical process model links behavioral aging and lifespan in C. elegans
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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