The broad objective of the Metabolic Assessment Core is to help investigators achieve both their own Project aims and these two key Program goals: to elucidate pathways and mechanisms that regulate aging rate and lifelong metabolic output in several species; and to establish a """"""""metabolic profile of longevity"""""""" (select assays, results of which correlate with longevity even for young adults, unified under a rational sample-preparation scheme) that may be applied across taxa. There are two underlying hypotheses: that a genetic predisposition for longevity manifests itself in the metabolic and oxidative protection pathways of youthful adults, and that predictors of longevity and vigor that generalize across phyla will relate also to human health. The former will be tested through joint efforts of this Core and the five Projects, whereas testing the latter is clearly beyond the scope of this proposal. Core B will be structured as a flail-service resource core, offering two services:
The Specific Aims """""""" (1) Chromatography Service: Quantify intermediary metabolites, damage markers, protective agents, energy charge and indices of redox status by high-performance liquid chromatography (HPLC) with coulometric-array electrochemical (HPLC-EC), fluorescence (HPLC-F), and UV (HPLC-UV) detection options; integrate our results and those of others within a searchable database. (2) Respirometry Service: Measure oxygen (O2) and carbon dioxide (CO2) respiration of rodents, flies and worms by flow and constant-volume respirometry to assess metabolic rate and lifetime metabolic output; monitor dissolved O2 in cell, tissue and whole-animal suspensions to assess mitochondrial O2 utilization pathways and bioenergetic parameters; and enter respirometry data into a database managed by the Chromatography Service. The strategy for achieving overall and specific goals includes purchases of a HPLC system with coulometric, fluorescence and UV detectors, relational database software, and a respirometry system with O2 and CO2 analyzers. Core B will not charge Projects for assessments but will train Project personnel to assume hands-on responsibility for validated, routine assays. New findings emerging from Projects in the Program as well as findings and methodologies from the community at large will be relevant to a metabolic profile for longevity. Core B is charged with adapting methodologies underlying such findings the model systems and sample types in the Program, thus permitting tests of the generality of such findings across phyla and elucidation of a global metabolic profile of longevity giving insight into life-span regulation.
Showing the most recent 10 out of 18 publications
