Abstract
ABSTRACTSarcopenia 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.
Highlights
Aging is a complex phenomenon, which can be defined as a progressive deterioration of cell and tissue functions in living organisms with age (Gems, 2014)
We have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms
We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and improve healthspan in C. elegans
Summary
Aging is a complex phenomenon, which can be defined as a progressive deterioration of cell and tissue functions in living organisms with age (Gems, 2014). Former studies relied almost exclusively on manual scoring of myofilament organization and the appearance of muscle defects (Ben-Zvi et al, 2009; Brehme et al, 2014; Glenn et al, 2004; Herndon et al, 2002; Karady et al, 2013; Lamarche et al, 2018; Meissner et al, 2009; Meissner et al, 2011). Such quantifications are prone to observer bias and are not very sensitive. To prove its potential for screening, we validated our model on a biologically relevant mutant displaying delayed sarcopenia (Depuydt et al, 2013; Herndon et al, 2002; Wang et al, 2019)
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