Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans

Abstract

Clk mutants of Caenorhabditis elegans are characterised by an overall slow down of temporal processes and increase in life span. It was hypothesised that Clk mutations slow down the pace of many cellular functions and lower the rate of energy metabolism, possibly resulting in slower production of reactive oxygen species which in turn could result in slower ageing [1–3]. We tested this hypothesis by measuring respiration rates, light production capacities [4] (a measure of metabolic potential) and ATP levels in various strains harbouring mutant alleles of the Clk genes clk-1 and gro-1 and of three other genes that interact with the Clk genes. We found a mild reduction of oxygen consumption rates but little alteration of metabolic capacities in the single Clk mutants during the first 4–5 days of their adult lives, relative to the wild-type strain. This difference tended to fade away with increasing age, however, and aged Clk mutants eventually retained higher metabolic capacities than the wild-type control strain N2. These profiles are suggestive of physiological time being retarded, relative to chronological time in Clk mutants. Ageing clk-1 and gro-1 mutants also retained substantially elevated ATP levels relative to the N2 strain, and the simultaneous presence of mutations in daf-2 or age-1 – genes that affect longevity – boosted this effect. Thus, energy production and consumption appear to be uncoupled in these mutants. Mutation in the transcription factor daf-16 suppressed the Age and ATP phenotypes, but not the reduction of respiration rate imparted by mutation in clk-1.