Ammonia, respiration, and longevity in nematodes: Insights on metabolic regulation of life span from temporal rescaling

To better understand metabolic correlates of longevity, we used a graphical technique to compare the adult temporal patterns of several markers of met abolic activity - ammonia elimination, oxygen consumption rate, ATP levels, and (in freeze-permeabilized worms) the rate of NADPH-activated, lucigenin -mediated superoxide formation - as observed by us and others in normal and long-lived mutant Caenorhabditis elegans strains. All of these traits decl ined with time, and when their logarithms were plotted against time, appear ed reasonably linear for most of the duration of the experiments. The profi les for ammonia output conformed well to parallel regression lines; those f or the other metabolic parameters varied widely in slope as originally plot ted by the authors, but much less so when replotted as logarithms against a djusted time, scaled by the reciprocal of strain longevity, This is consist ent with coregulation of life span, respiration rate, ATP levels, lucigenin reactivity, but not ammonia excretion, by a physiological clock distinguis hable from chronologic time. Plots, scaled appropriately for equalized slop es, highlighted y-axis intercept differences among strains. On rescaled plo ts, these constitute deviations from the expectation based on 'strain-speci fic clock' differences alone. With one exception, y-intercept effects were observed only for mutants in an insulin-like signaling pathway.