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

Abstract

To better understand metabolic correlates of longevity, we used a graphical technique to compare the adult temporal patterns of several markers of metabolic 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 declined with time, and when their logarithms were plotted against time, appeared reasonably linear for most of the duration of the experiments. The profiles for ammonia output conformed well to parallel regression lines; those for the other metabolic parameters varied widely in slope as originally plotted by the authors, but much less so when replotted as logarithms against adjusted time, scaled by the reciprocal of strain longevity. This is consistent with coregulation of life span, respiration rate, ATP levels, lucigenin reactivity, but not ammonia excretion, by a physiological clock distinguishable from chronologic time. Plots, scaled appropriately for equalized slopes, highlighted y-axis intercept differences among strains. On rescaled plots, these constitute deviations from the expectation based on 'strain-specific clock' differences alone. With one exception, y-intercept effects were observed only for mutants in an insulin-like signaling pathway.