Final Report Summary - NEURONAGE (Molecular Basis of Neuronal Ageing)
Ageing is associated with marked decrease of neuronal function and increased susceptibility to neurodegeneration, in organisms as diverse as the lowly worm Caenorhabditis elegans and humans. Although, age-related deterioration of the nervous system is a universal phenomenon, its cellular and molecular underpinnings remain obscure. What mechanisms are responsible for the detrimental effects of ageing on neuronal function? The aim of the project is to address this fundamental problem. We have implemented an interdisciplinary approach, combining the power of C. elegans, a highly malleable genetic model which offers a precisely defined nervous system, with state-of-the-art microfluidics and optical imaging technologies, to manipulate and monitor neuronal activity during ageing, in vivo. The main outcomes of the project are as follows:
• Development of a microfluidics platform for high-throughput manipulation and imaging of specific neurons in individual animals, in vivo.
• Use the platform for monitor neuronal function during ageing in isogenic populations of wild type animals, long-lived mutants and animals under caloric restriction, a condition known to extend lifespan from yeast to primates
• Elucidation of how ageing modulates susceptibility to neuronal damage in nematode models of human neurodegenerative disorders.
• Identification and characterization of modifiers of resistance to ageing-inflicted neuronal function decline.
Together, these studies promote understanding of age-related breakdown of neuronal function and provide critical insights with broad relevance to human health and quality of life.
• Development of a microfluidics platform for high-throughput manipulation and imaging of specific neurons in individual animals, in vivo.
• Use the platform for monitor neuronal function during ageing in isogenic populations of wild type animals, long-lived mutants and animals under caloric restriction, a condition known to extend lifespan from yeast to primates
• Elucidation of how ageing modulates susceptibility to neuronal damage in nematode models of human neurodegenerative disorders.
• Identification and characterization of modifiers of resistance to ageing-inflicted neuronal function decline.
Together, these studies promote understanding of age-related breakdown of neuronal function and provide critical insights with broad relevance to human health and quality of life.