Aging is the single most important factor determining the onset of human disease in developed countries.  With current demographic trends indicating that the number of individuals over the age of 65 in the US will rise from 35 million in the year 2000 (13% of the total population) to 70 million in the year 2030 (1 in 20) it is clear that an understanding of the processes that underpin aging and age-related disease represents a key challenge in the biomedical sciences.  

In recent years there have been huge advances in our understanding of the aging process and many of these have stemmed from genetic analysis of the nematode Caenorhabditis elegans (C. elegans). These studies have identified endocrine signaling pathways conserved between worms and mammals that include receptors whose endogenous ligands are small, lipid-derived hormones that cannot be identified by genetic approaches alone.  These hormone pathways are also tractable drug targets and thus the identification of small molecule regulators of their activity could lead to rational drug development for aging and age-related disease.  Given the conservation of aging pathways between species, this approach is likely to open up new therapeutic avenues for combating human aging and age-related disease. 

My lab uses an interdisciplinary approach that combines chemical screens, analytical chemistry, biochemistry and genetics to identify small molecule regulators of aging in C. elegans and determine their molecular mechanism of action.  Using this approach we have recently identified a group of lipid signaling molecules called N-acylethanolamines (NAEs) in the worm, one of which shows similarity to mammalian endocannabinoids and affects nematode lifespan by modulating pathways involved in nutrient sensing and dietary restriction.  Endocannabinoid pathways in mammals are well known to be involved in nutrient sensing and energy balance but a role in the aging process has not yet been demonstrated.  The discovery of NAEs and endocannabinoids in C. elegans not only provides a means of further investigating the role of these important signaling molecules in lifespan determination but also brings a powerful genetic system to the study of NAE physiology.