Previous work has shown that reduction-of-function mutations in the genes
daf-2 and
age-1 can increase adult life (Age phenotype) of Caenorhabditis elegans and that certain
daf-12 alleles considerably amplify this effect in
daf-2;
daf-12 doubles. We have measured the light production potential (LPP) and alkaline phosphatase (ALP) and protein tyrosine kinase (PTK) activity levels as suitable biochemical markers to further investigate genetic interactions between these genes. The light production assay measures superoxide anion production by freeze-thawed worms in assay medium containing sufficient amounts of nicotineamide adenine dinucleotide, reduced form (NADH) and nicotineamide adenine dinucleotide phosphate, reduce form (NADPH) to drive the chemiluminescent reaction at maximal speed, and 5 mM cyanide to fully repress cytosolic superoxide dismutase (SOD). This assay thus provides an estimate of the maximum output of the metabolic pathways involved at the instant of freeze-fixation, and under the conditions of the assay. LPP and PTK activities decreased similarly in
daf-12(
m20), and a control strain that had wild-type alleles of
daf-12,
age-1, and
daf-2. The age-dependent decrease of LPP and PTK was reduced in
age-1(
hx542) and
age-1(
hx542);
daf-2(
e1370), and virtually absent in
daf-2(
e1370) and
daf-2(
e1370);
daf-12(
m20) mutant worms. ALP activity increased with age in non-Age genotypes and showed little, if any, age-dependent alteration in
daf-2(
e1370) and
daf-2(
e1370);
daf-12(
m20) mutant worms. Mutation in both
age-1 and
daf-2 caused no stronger phenotype than a single mutation as estimated by LPP, PTK, and ALP. We propose that (a)
daf-2 is the major effector of metabolic activity during adult life, (b)
daf-2 downregulates metabolic activity with increasing age, and (c)
daf-12 stimulates oxygen consumption independently of
daf-2.