The biological processes that are associated with the physiological fitness state of a cell comprise a diverse set of molecular events. Reactive oxygen species (ROS), mitochondrial dysfunction, telomere shortening, genomic instability, epigenetic changes, protein aggregation, and down-regulation of quality control mechanisms are all hallmarks of cellular decline. Stress-related and decline-related changes can be assayed, but usually through means that are highly disruptive to living cells and tissues. Biomarkers for organismal decline and aging are urgently needed for diagnostic and drug development. Our goal in this study is to provide a proof-of-concept for a non-invasive assay of global molecular events in the cytoplasm of living animals. We show that Microwave Dielectric Spectroscopy (MDS) can be used to determine the hydration state of the intracellular environment in live C. elegans worms. MDS spectra were correlative with altered states in the cellular protein folding environment known to be associated with previously described mutations in the C. elegans lifespan and stress-response pathways.