Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans
Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model fo...
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Published in | Disease models & mechanisms Vol. 14; no. 11 |
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Language | English |
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01.11.2021
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Abstract | Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of ageing myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens in this model organism to identify modulators that mitigate age-related muscle frailty and thus improve healthspan. |
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AbstractList | Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of ageing myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens in this model organism to identify modulators that mitigate age-related muscle frailty and thus improve healthspan. ABSTRACT Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of ageing myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens in this model organism to identify modulators that mitigate age-related muscle frailty and thus improve healthspan. Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of ageing myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens in this model organism to identify modulators that mitigate age-related muscle frailty and thus improve healthspan. Summary: A tool for quantitative image analysis of muscle deterioration that allows predicting healthspan in the nematode model Caenorhabditis elegans and may lead to the first C. elegans -based high-throughput sarcopenia screening platform. |
Author | Braeckman, Bart P Dhondt, Ineke Verschuuren, Clara Zečić, Aleksandra De Vos, Winnok H Loier, Tim |
AuthorAffiliation | 2 Laboratory of Cell Biology and Histology, Department of Veterinary Sciences , University of Antwerp , 2610 Antwerp , Belgium 1 Biology Department , Ghent University , K.L. Ledeganckstraat 35, B-9000 Ghent , Belgium |
AuthorAffiliation_xml | – name: 2 Laboratory of Cell Biology and Histology, Department of Veterinary Sciences , University of Antwerp , 2610 Antwerp , Belgium – name: 1 Biology Department , Ghent University , K.L. Ledeganckstraat 35, B-9000 Ghent , Belgium |
Author_xml | – sequence: 1 givenname: Ineke surname: Dhondt fullname: Dhondt, Ineke organization: Biology Department, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium – sequence: 2 givenname: Clara surname: Verschuuren fullname: Verschuuren, Clara organization: Biology Department, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium – sequence: 3 givenname: Aleksandra orcidid: 0000-0003-4883-7881 surname: Zečić fullname: Zečić, Aleksandra organization: Biology Department, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium – sequence: 4 givenname: Tim surname: Loier fullname: Loier, Tim organization: Biology Department, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium – sequence: 5 givenname: Bart P surname: Braeckman fullname: Braeckman, Bart P organization: Biology Department, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium – sequence: 6 givenname: Winnok H orcidid: 0000-0003-0960-6781 surname: De Vos fullname: De Vos, Winnok H organization: Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium |
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Keywords | Sarcopenia C. elegans Image analysis Healthspan Phenotype prediction Ageing |
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Snippet | Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan... ABSTRACT Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable... |
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SubjectTerms | Age ageing Aging Aging - physiology Animals Automation Biomarkers c. elegans C. Elegans as a Disease Model Caenorhabditis elegans - genetics Caenorhabditis elegans Proteins - genetics Genotype & phenotype healthspan Humans image analysis Longevity - genetics Morphology Muscles Nematodes phenotype prediction Sarcopenia Trends |
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Title | Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans |
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