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Metabolic flexibility: breaking down food effectively to prolong life

Project description

Revealing metabolic processes to prolong healthy lifespan

The world’s aging population poses a significant burden on healthcare, societies and economies due to the prevalence of age-associated diseases. While reduced caloric intake and increased exercise have shown potential in improving the health of seniors, there is a need for more effective methods. In line with this goal, the EU-funded MetaFlex project aims to identify new pathways for anti-ageing treatments and shed light on the connection between metabolism and ageing. The project builds upon recent discoveries regarding the dysregulation of fat metabolism in aged mice, which leads to weight gain and glucose intolerance. Through experimental research, the project will investigate how the breakdown of nutrients can enhance metabolic flexibility, ultimately supporting healthy ageing.

Objective

Aging has long been considered a passive process. More recently studies have defined an important, active role for metabolic pathways in aging and age-related diseases. I have previously demonstrated a marked dysregulation of fat metabolism in aged mice that contributes to their overweight and glucose intolerance. Here, I propose a model that links healthy aging to efficient processing of nutrients, a state termed metabolic flexibility: reducing protein or carbohydrate metabolism will strongly stimulate fat breakdown. I suggest that improved metabolic flexibility will thus prevent the accumulation of lipids and protect against its detrimental effects.

In this project, I aim to elucidate how nutrient breakdown is regulated and can be adapted to improve metabolic flexibility and promote healthy aging. I will use C. elegans, as well as mammalian models and human population studies. Specifically, I aim to (1) dissect the molecular actors of metabolic aging pathways; (2) identify genes that translate nutritional cues to lifespan variation; (3) find novel genetic regulators that prevent toxicity and accelerated aging caused by fat-rich diets; (4) identify associations between variants in genes involved in metabolic flexibility and aging phenotypes in humans.

This set of experiments should clarify the role of nutrient breakdown and metabolic flexibility in aging. Better understanding of these processes can lead to a prolonged healthy state of aged individuals.

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Host institution

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Net EU contribution
€ 1 499 446,25
Address
MEIBERGDREEF 15
1105AZ Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 446,25

Beneficiaries (1)