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Modulation of complex lipids to promote healthy aging

Project description

Exploring complex lipid metabolism for healthy ageing

New research reveals that genetic and pharmacological interventions can effectively control the ageing process, thereby reducing the risk of age-related diseases. Dysregulated lipids play a crucial role in age-related conditions. A lipidomics analysis conducted on aged mice uncovered the accumulation of bis(monoacylglycero)phosphate (BMP) in all tissues. This has been linked to PLA2G15, which is involved in BMP production. Knocking down PLA2G15 in worms has resulted in an extended lifespan, suggesting its significance in the ageing process. The MSCA-funded LipidAge project explores how targeting complex lipid metabolism can promote healthy ageing. The project will investigate the role of complex lipids, specifically BMPs, in the ageing process and explore how these pathways and their effects on lysosomal functions influence healthy ageing.

Objective

Aging has long been considered a passive process that could not be reverted. Fortunately, it is now clear from genetic and pharmacological intervention studies that aging is actively regulated and can be influenced to reduce the burden of age-related diseases, such as neurodegenerative and metabolic diseases. Studies in various organisms established the importance of dysregulated lipids in the development of aging and age-related diseases. It remains unclear, however, how complex lipids and lipid metabolism causally affect aging, and the mechanisms are poorly understood. In my preliminary lipidomics analysis in ten different tissues of aged mice, I found a striking accumulation of bis(monoacylglycero)-phosphate (BMP) in all tissues. While little is known about BMPs, one lysosomal enzyme that has been described to contribute to its production is PLA2G15. Remarkably, knocking down Pla2g15 in worms leads to a significant lifespan extension. Together, these findings suggest a causal involvement of Pla2g15 in aging. I hypothesize that targeting complex lipid metabolism could promote healthy aging. Therefore, the main goal of LipidAge is to unravel the role of complex lipids, specifically BMPs in the development of aging, and how these pathways and their downstream effects impinge on lysosomal functions and healthy aging. I will use human and mouse lipid data profiles, worm C. elegans, and apply a combination of molecular, biochemical and phenotypic experiments with a focus on lipids and aging. These experiments will lead to a better understanding of conserved complex lipid changes, and the role of Pla2g15 in the BMP synthesis cascade relevant for health and disease during aging.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

STICHTING AMSTERDAM UMC
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 203 464,32
Total cost

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