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

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 mut...

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Autores principales: Oswal, Natasha, Martin, Olivier M. F., Stroustrup, Sofia, Bruckner, Monika Anna Matusiak, Stroustrup, Nicholas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524676/
https://www.ncbi.nlm.nih.gov/pubmed/36178967
http://dx.doi.org/10.1371/journal.pcbi.1010415
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author Oswal, Natasha
Martin, Olivier M. F.
Stroustrup, Sofia
Bruckner, Monika Anna Matusiak
Stroustrup, Nicholas
author_facet Oswal, Natasha
Martin, Olivier M. F.
Stroustrup, Sofia
Bruckner, Monika Anna Matusiak
Stroustrup, Nicholas
author_sort Oswal, Natasha
collection PubMed
description 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.
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spelling pubmed-95246762022-10-01 A hierarchical process model links behavioral aging and lifespan in C. elegans Oswal, Natasha Martin, Olivier M. F. Stroustrup, Sofia Bruckner, Monika Anna Matusiak Stroustrup, Nicholas PLoS Comput Biol Research Article 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. Public Library of Science 2022-09-30 /pmc/articles/PMC9524676/ /pubmed/36178967 http://dx.doi.org/10.1371/journal.pcbi.1010415 Text en © 2022 Oswal et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Oswal, Natasha
Martin, Olivier M. F.
Stroustrup, Sofia
Bruckner, Monika Anna Matusiak
Stroustrup, Nicholas
A hierarchical process model links behavioral aging and lifespan in C. elegans
title A hierarchical process model links behavioral aging and lifespan in C. elegans
title_full A hierarchical process model links behavioral aging and lifespan in C. elegans
title_fullStr A hierarchical process model links behavioral aging and lifespan in C. elegans
title_full_unstemmed A hierarchical process model links behavioral aging and lifespan in C. elegans
title_short A hierarchical process model links behavioral aging and lifespan in C. elegans
title_sort hierarchical process model links behavioral aging and lifespan in c. elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524676/
https://www.ncbi.nlm.nih.gov/pubmed/36178967
http://dx.doi.org/10.1371/journal.pcbi.1010415
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