We propose to investigate the mechanism by which nutritional restriction increases the lifespan and slows aging, using as a model system the small, genetically tractable and short-lived nematode Caenorhabditis elegans. We have constructed a multiparametric index of physiological age for this animal and will use it to determine the effects of various perturbations (nutritional restriction, altered growth temperature, inhibitors of energy metabolism) on the """"""""rate of aging"""""""". We will also measure the effects of nutritional restriction on a series of biochemical and metabolic parameters related to energy generation and utilization (adenylate energy charge, levels of storage compounds, key metabolic intermediates), in the hope of identifying which of these are most closely correlated with aging rate. We propose to isolate new mutants with possibly altered rates of aging, determine which of these suffer from nutritional deprivation by reason of reduced food intake resulting from the mutational lesion and attempt to identify a class of mutants which ages more slowly despite normal rates of food intake. The specific classes of mutants to be sought are: a) Slow growing mutants; b) Stage-specific developmental arrest mutants and C) Mutants which show unusual longevity in the already long-lived """"""""dauer- larva"""""""" state.
| Russell, R L; Seppa, R I (1987) Genetic and environmental manipulation of aging in Caenorhabditis elegans. Basic Life Sci 42:35-48 |
| Clokey, G V; Jacobson, L A (1986) The autofluorescent ""lipofuscin granules"" in the intestinal cells of Caenorhabditis elegans are secondary lysosomes. Mech Ageing Dev 35:79-94 |
