FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans.

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.

An alternative food source for metabolism and longevity studies in Caenorhabditis elegans.

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.

Role of hemoglobin in hemoglobin-based remediation of the crude oil-contaminated soil.

This study investigated the changes in the indigenous microbial community structure with hemoglobin (Hb) application to determine the role of Hb in Hb-based remediation of crude oil-contaminated soil. The phylogenetic diversity of the bacterial community showed that the Hb addition selected surfactants-producing species, thereby, promoting TPH degradation. The significant increase in the CO2 generation, which can be related to the increase in the bacterial abundance inferred from the 16S rRNA gene copy number, supports the enhanced TPH degradation with Hb application. The similar residual TPH concentrations in the presence of only hydrogen peroxide (H2O2) and both Hb and H2O2 suggested that the role of Hb as a catalyst was not as significant as the role of Hb as a nutrient. Also, in the presence of H2O2, a greater recovery of the microbial community structure was observed with the double Hb injection than the single Hb injection. Overall, this study shows that the Hb-based remediation strategies via microbial metabolism can be successfully applied to remediate the crude-oil contaminated Kuwaiti soil.