Modulation of ageing by genetic knock-out, phototherapy and drugs in the C. elegans worm

Assisting healthy ageing is a key goal of 21st century healthcare. Caenorhabditis elegans is an attractive model species for ageing studies because of its short life cycle (ca. 3 days), its rapid development, and the homology of its genome with that of humans. Clinical phenotypic studies indicated that different flavin-containing monooxygenase (FMO) and various diol compounds had a role in longevity extension in C. elegans. New, endogenous functions of FMOs in C. elegans were determined, including fmo-4, the loss of which resulted in significant phenotypic differences and enhanced lifespan, compared with wild type worms. Nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of extracts of different C. elegans FMO mutants at different life stages and of diol-treated worms revealed biochemistry that correlated with genotype and influence on lifespan. Meanwhile, as seen in studies with higher model organisms, irradiation of C. elegans with 670 nm red light also increased ATP levels, improved mitochondrial dynamics and enhanced worm motility. Infra-red (1072 nm) exposure was already reported to increase C. elegans lifespan. The effects of the chemical, physical and genetic interventions on C. elegans provide clues about the mechanisms and possible strategies to extend healthy lifespan in human old age.