Aging - protein turnover
General information about C. elegans and aging can be found here.
In order to study the role of energy metabolism and stress defense in the aging process of Caenorhabditis elegans, we developed and adapted several assays during the last few years. Apart from direct measurements of metabolic rate (oxygen consumption, heat generation), we used techniques that quantify ATP-levels, superoxide production potential (lucigenin assay), and bioreduction capacity (XTT assay) (Braeckman et al., 2002a). Microtiterplate assays for superoxide dismutase (Lenaerts et al., 2002) and catalase activities (two reactive oxygen species scavengers) were developed.
In contrast to general anticipation, metabolic rates of long-lived mutants tested in our lab, were not lower compared to wild type. Mutation in daf-2 can lead to extreme longevity (Kenyon et al., 1993). The metabolic rate of daf-2 mutants is not decreased as a whole. Instead a shift towards higher catabolic efficiency seems to occur (low heat output, unchanged oxygen consumption and high ATP levels)(Braeckman et al., 2002b). We also found a remarkable increase of catalase and SOD activity in this mutant (Houthoofd et al., 2003). These high activities probably protect the mutant against oxidative damage and might lead to the observed life span extension. Life span extension in Clk (clock) mutants is less prominent compared to daf-2. In Clks (clk-1, clk-2, clk-3, gro-1) we found wild-type levels for most of the energy metabolism and ROS scavenger activities (Braeckman et al., 1999; 2002c). The exact molecular mechanism of Clk longevity remains unclear.
Another way to cope with molecular damage
is increased breakdown of damaged molecules together with increased de
novo synthesis. We are currently interested in the role of
turnover in life-span determination of C. elegans.