Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.

Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling.

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MethodsWe utilized two methods for our university travel GHG emissions accounting, both of which utilize emission factors, Great Circle Distances (GCDs), and ground vehicle miles. The first method (EPA method) relied on CO2, CH4, and N2O emission factors from the EPA. 3 Ground vehicle emission factors were based on data from the EPA's Inventory of U.S. Greenhouse Gas Emissions and Sinks: 1990-2015 and the Federal Highway Administration Highway Statistics 2015. Car and bus emission factors were standardized to vehicle miles while train emission factors were standardized to passenger-miles. Air travel emission factors, standardized to passenger-miles, were based on 2017 Guidelines to Defra/DECC's GHG Conversion Factors for Company Reporting. These air travel emission factors were segmented based on travel distance, with different factors for trips <300 miles, trips between 300 and 2,300 miles, and trips >2,300 miles. Additionally, the most recent global warming potentials (GWPs) were used to convert all emissions to GHG units of tCO2e. The second method (SIMAP method) relied on CO2, CH4, and N2O emission factors from SIMAP. 4 SIMAP is a GHG accounting tool designed by the University of New Hampshire and commonly used by other organizations. Its ground vehicle emission factors, standardized to vehicle miles, are based on U.S. Department of Transportation fleet emission factors and fuel economies. Its air travel emission factors, standardized to passenger-miles, were calculated using the EPA's National Emission Inventory for combustion factors and passenger-mile data from the U.S. Bureau of Transportation Statistics.