Stress responses and dynamic equilibrium: key determinants of ageing in the Caenorhabditis elegans clk-1 mutant

Systems biology offers valuable insights into ageing by integrating experimental data with mathematical models and bioinformatics tools. Long-lived mutants of Caenorhabditis elegans, particularly clk-1, have provided extensive data on the ageing mechanisms. The clk-1 gene, which encodes a ubiquitin precursor, shows a pleiotropic phenotype characterized by slow behaviour, high mitochondrial reactive oxygen species levels, autophagy and metabolic changes. However, the link between these changes and lifespan extension remains unclear. Using a Boolean network, we modelled genetic interactions and derived differential equations for a continuous approach. Our results highlight that aak-2 (AMPK) is crucial for clk-1 lifespan extension owing to its role in stress-response regulation. We introduced a health index based on the attrition of neuromuscular behaviours to assess the health of various strains. Our findings suggest that while stress responses may enhance lifespan, overall health is determined by the extent of the damage.