Cells clog up with waste as they age, and a newly discovered delivery route for fat-digesting enzymes could help keep them clean. This matters because the build-up of undegraded material inside cells is linked to age-related diseases, including neurodegeneration and cancer. The lysosome—a cellular compartment that acts as a waste-processing hub—relies on specific enzymes to break down different types of debris. One key group of enzymes, lipases, degrades fats. The researchers have identified a previously unknown mechanism that cells use to deliver lipases to lysosomes. Understanding how this delivery system works, and what goes wrong when it fails, could reveal a fundamental cause of cellular ageing. This is primarily fundamental science. The immediate goal is to map the molecular machinery of this lipase delivery pathway and test whether boosting it can extend lifespan in model organisms. If successful, the work would provide a concrete target for interventions aimed at improving healthy ageing—potentially delaying the onset of age-related disorders. The tools and insights generated will also be useful for other labs studying lysosome biology, fat metabolism, and cellular waste management.
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Aging is associated with a decline in the ability of cells to degrade unwanted material. The build-up of undegraded material in cells can result in their dysfunction and is therefore associated with various aging-related diseases, including neurodegeneration and cancer. One of the major cellular hubs that mediate degradation processes is known as the lysosome. Lysosomes are specialised compartments that can degrade a wide range of substrates through the activities of specific enzymes. This localised activity of enzymes in lysosomes is essential to regulate their function. Therefore, cells have developed various mechanisms to deliver enzymes to lysosomes and ensure their restrained activity. In this proposal, we aim to understand how lipids are degraded in lysosomes. The degradation of lipids is mediated by a subset of enzymes known as lipases. We have identified a novel mechanism in cells that delivers lipases to lysosomes. We aim to understand the molecular bases of this mechanism and what happens in cells when it is disrupted. We will address whether enhancing this lipase delivery pathway can prolong longevity in order to confirm its relevance during aging. This proposal aims to understand mechanisms underlying aging and we predict that our findings may help us improve healthy aging in humans. Our goal is to uncover the molecular details of how our cells function and remain healthy in order to help us design methods to improve healthy aging and delay the onset of disorders in humans. The findings and tools generated during the course of this study will also have wider implications and utilities across multiple research areas.
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