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Here we present ADH-1 as a unique anti-aging molecule. It is unique because it is not possible to live longer without ADH-1. It is also unique because activating ADH-1 is all that is needed to live longer. We found both of these claims to be true in yeast and the nematode C. elegans, but we also have strong clues suggesting that ADH1 may be necessary and sufficient for heathy aging and long life in mammals including humans. 

O'Rourke Eyleen C elegans Obesity Aging Lab University of Virginia

A lysosome-centered view of nutrient homeostasis

Here we describe the role of the lysosome in nutrient mobilization and signalling other organelles, distant tissues, and even themselves to ensure energy homeostasis inspite of fluctuations in energy intake. Altogether, we provide an integrated view on how lysosomes contribute to organismal homeostasis and health.

O'Rourke Eyleen C elegans Obesity Aging Lab University of Virginia
Nature Cell Biology, 2013

MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability

Energy is stored in the form of fat when food is available. When food becomes scarce organims activate genetic programs that maximize their chances of survival until food becomes again available. Unbiased genome searches allow us to discover a molecular switch that promotes fat accumulation while food is availble and fat utilization during fasting. Animals that cannot activate this survival program die prematurely of starvation. This program orchestrated by the transcription factors mxl-3 and hlh-30 is conserved in worms, flies, mice and human cells in culture. Therefore, this ancient metabolic program could become a target for the treatment of metabolic disease in humans.

O'Rourke Eyleen C elegans Obesity Aging Lab University of Virginia

Omega-Polyunsaturated Fatty Acids Increase Lifespan through the Activation of Autophagy

In this paper we described that feeding omega-6 fatty acids to C. elegans or adding them to cultured human cells activates a cellular renewal process called autophagy and extends lifespan. Autophagy is a process by which defective or worn-out cellular components and molecules are broken down for removal or recycling. Autophagy becomes less efficient as we age leading to several important diseases of aging ranging from cancer to neurodegeneration. We thus uncover how these commonly used dietary supplements, omega-3 and omega-6 fatty acids, act to improve human health. We would also like to direct you to read the recommendations from the American Heart Association  about NOT reducing the consumption of omega-6 fatty acids (AHA button below).

O'Rourke Eyleen C elegans Obesity Aging Lab University of Virginia
Science, 2009

Fat Metabolism Links Germline Stem Cells and Longevity in C.elegans

We here describe the first direct link between fat metabolism and aging. We discovered and characterized a lipase (enzyme breaking down fats) whose activation is sufficient to extend lifespan. We also show that this lipase, that we named LIPL-4, is activated in long-lived mutant animals, and that knock-down of the lipase gene in the long-lived mutants attenuates their longevity. This suggests that drug-triggered activation of this lipase or dietary supplemetation with its degradation products could extend lifespan.


CORRIGENDUM: This paper claims glp-1 mutant animals are lean. We showed this is not the case in O'Rourke & Soukas et al, Cell Metabolism 2010.

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