Abstract
Ageing is the primary risk factor for cancer, cardiovascular disease, and dementia. While healthy ageing is intimately linked to metabolism and protein homeostasis (proteostasis), the interplay at the heart of this relationship is unknown. Therefore, we will combine fluorescence lifetime imaging, proteostasis sensors, and reporter systems in Caenorhabditis elegans, to study changes in NADH and NADPH levels, mitochondrial morphology, and protein folding capacity, at single-cell resolution, in intact ageing tissues. By combining this approach with genetic screening, gene expression analyses, and readouts of mitochondrial function, it will be possible to establish how age-related metabolic changes converge on proteostasis and disease-susceptibility.
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