Nervous System Ageing

Bénard, Claire; Doitsidou, Maria

doi:10.1007/978-3-319-44703-2_8

Cited by 9 publications

(11 citation statements)

References 156 publications

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“…The Caenorhabditis elegans nervous system is not an exception and undergoes morphological and functional deterioration under these conditions. Morphological phenotypes indicative of neurodegeneration in this roundworm include somatic outgrowth, distorted soma, branched and wavy dendrites, and dendritic beading [ 2 , 8 , 12 – 18 ]. For instance, degenerative axonal beading has been observed and identified previously in various neurons such as ALM, PLM, and HSN [ 8 , 19 – 22 ], and in dopaminergic neurons upon exposure to genotoxins [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock

2020

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Background Access to quantitative information is crucial to obtain a deeper understanding of biological systems. In addition to being low-throughput, traditional image-based analysis is mostly limited to error-prone qualitative or semi-quantitative assessment of phenotypes, particularly for complex subcellular morphologies. The PVD neuron in Caenorhabditis elegans, which is responsible for harsh touch and thermosensation, undergoes structural degeneration as nematodes age characterized by the appearance of dendritic protrusions. Analysis of these neurodegenerative patterns is labor-intensive and limited to qualitative assessment. Results In this work, we apply deep learning to perform quantitative image-based analysis of complex neurodegeneration patterns exhibited by the PVD neuron in C. elegans. We apply a convolutional neural network algorithm (Mask R-CNN) to identify neurodegenerative subcellular protrusions that appear after cold-shock or as a result of aging. A multiparametric phenotypic profile captures the unique morphological changes induced by each perturbation. We identify that acute cold-shock-induced neurodegeneration is reversible and depends on rearing temperature and, importantly, that aging and cold-shock induce distinct neuronal beading patterns. Conclusion The results of this work indicate that implementing deep learning for challenging image segmentation of PVD neurodegeneration enables quantitatively tracking subtle morphological changes in an unbiased manner. This analysis revealed that distinct patterns of morphological alteration are induced by aging and cold-shock, suggesting different mechanisms at play. This approach can be used to identify the molecular components involved in orchestrating neurodegeneration and to characterize the effect of other stressors on PVD degeneration.

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Section: Introductionmentioning

confidence: 99%

Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock

2020

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“…The nervous system in C. elegans undergoes morphological and functional decline due to aging 14,18 . Morphological changes in PVD include dendritic outgrowth and beading, which become more common as animals age, as evidenced in Figure 3a.…”

Section: Deep Phenotyping Of Age Induced Pvd Neurodegenerationmentioning

confidence: 99%

“…The Caenorhabditis elegans nervous system is not an exception and undergoes morphological and functional deterioration under these conditions. Morphological phenotypes indicative of neurodegeneration in this roundworm include somatic outgrowth, distorted soma, branched and wavy dendrites, and dendritic beading 2,8,[12][13][14][15][16][17][18] . The ability of neurons to recover from degeneration has also been studied.…”

Section: Introductionmentioning

confidence: 99%

Deep learning-enabled phenotyping reveals distinct patterns of neurodegeneration induced by aging and cold-shock

Saberi-Bosari

Flores

San-Miguel

2020

Preprint

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Access to quantitative information is crucial to obtain a deeper understanding of biological systems. In addition to being low-throughput, traditional image-based analysis is mostly limited to error-prone qualitative or semi-quantitative assessment of phenotypes, particularly for complex subcellular morphologies. In this work, we apply deep learning to perform quantitative imagebased analysis of complex neurodegeneration patterns exhibited by the PVD neuron in C. elegans. We apply a Convolutional Neural Network algorithm (Mask R-CNN) to identify neurodegenerative sub-cellular protrusions that appear after cold-shock or as a result of aging. A multiparametric phenotypic profile captures the unique morphological changes induced by each perturbation. We identify that acute cold-shock-induced neurodegeneration is reversible and depends on rearing temperature, and importantly, that aging and cold-shock induce distinct neuronal beading patterns.

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“…control of ageing and longevity. The nervous system acts via diverse pathways to modulate organismal ageing and lifespan and itself undergoes age-dependent deterioration of its function and structure 91,92 . A full understanding of the causative relationships between agedependent decline of cells in the brain, organismal aging and longevity remains elusive.…”

Section: While Cellular Mechanisms Of Ageing Have Been the Focus Of Imentioning

confidence: 99%

Gap junctions in theC. elegansnervous system regulate ageing and lifespan

Vladis

Fischer

Digalaki

et al. 2019

Preprint

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The nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits in Caenorhabditis elegans have extensive and diverse impacts on lifespan. Loss of the neural innexin unc-9 increases longevity by a third and also strongly benefits healthspan. Unc-9 acts specifically in a glutamatergic circuit linked to mechanosensation. Absence of unc-9 depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal of unc-9 requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.is currently unknown whether gap junction coupling as a key intercellular communication channel contributes to the regulation of ageing and longevity.Here we set out to explore if gap junctions affect ageing using the nematode Caenorhabditis elegans, an outstanding model for studies on ageing 14,15 . We assayed the lifespan of loss-offunction mutants of most of the 25 C. elegans innexins and discovered that innexins have a significant impact on lifespan, some leading to an extension of lifespan while others shorten it. Surprisingly, most null mutations of neural innexins extended lifespan, with loss of unc-9, the most widely expressed innexin in the nervous system, increasing longevity by a third. Its selective removal from glutamatergic neurons led to an increase in lifespan and points to a mechanosensory circuit where UNC-9 regulates ageing. Our results show that UNC-9 alters the age-dependent decline of touch-sensing neurons and depends on functional touch sensation as well as reactive oxygen species to modulate lifespan. This study gives strong evidence to suggest an important and previously unknown role for gap junction intercellular communication in shaping ageing and longevity. ResultsThe C. elegans gap junction genes regulate longevity As there is extensive intercellular gap junction coupling in all organs of C. elegans, we hypothesised that gap junction channels may play specific roles in organismal ageing and longevity. The channel subunits encoded by 25 innexin genes show diverse, highly combinatorial, plastic and dynamic expression in virtually all organs and cells of this animal.The gap junction channels these innexins form play key roles in intercellular communication [16][17][18] . We asked if innexins influence longevity, which has not been known. To this end we performed lifespan assays in loss-of-function mutants of all innexins except inx-3, inx-12 and inx-13; these genes are essential for embryonic development or osmoregulation and their loss confers a lethal phenotype 18,19 . Loss-of-function mutants are availab...

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Nervous System Ageing

Cited by 9 publications

References 156 publications

Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock

Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock

Deep learning-enabled phenotyping reveals distinct patterns of neurodegeneration induced by aging and cold-shock

Gap junctions in theC. elegansnervous system regulate ageing and lifespan

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