How and why organisms age
All organisms have a set lifespan, influenced by both genetic and environmental factors. While the causes of ageing are not yet clearly defined, a central component is probably cell and DNA damage that accumulates over time. In most organisms, special 'repair proteins' correct damaged molecules, but with time these repair systems can malfunction, resulting in ageing. The EU-funded PIMT AND SIGNALING (Interaction between the protein repair enzyme L-isoaspartyl methyltransferase and insulin/IGF-1 signaling in mice and worms) project used mice and worms as models to study how organisms' repair systems influence ageing. Scientists looked at an enzyme called protein L-isoaspartyl methyltransferase (PIMT) that nearly all organisms, including bacteria, use to repair damaged proteins. Mice that cannot produce PIMT die prematurely, while flies and worms that produce large amounts of PIMT live longer, suggesting the repair enzyme delays ageing. A hormonal pathway called insulin/insulin-like growth factor-1 signalling (insulin-like signalling) is another molecular system implicated in the ageing process. Confirming both pathways' universal role in ageing, researchers found that PIMT and the insulin-like signalling pathway interact to extend the lifespan of both worms and mice. When researchers stopped mouse brain cells from producing PIMT, 60 % more damaged proteins accumulated in the PIMT-deficient brain cells than in normal cells. They also found that production of growth factor (a substance that promotes cell growth and healing) was affected in PIMT-deficient cells. This suggests there is a link between growth factor and lifespan extension by PIMT. Finally, scientists inactivated the PIMT pathway in zebrafish cells, which are used as models to study epileptic disorders. They observed a twitching movement of embryo tails, a sign of epilepsy in zebrafish. Since PIMT-deficient mice die prematurely from massive epileptic seizures, PIMT AND SIGNALING may have uncovered another role for PIMT: ensuring that brains function normally. PIMT AND SIGNALING demonstrated that model organisms like worms, mice and zebrafish are valuable tools to understand mechanisms of ageing. Ultimately, they may discover ways to reverse or delay the ageing process.
Keywords
Ageing, repair proteins, damaged molecules, protein L-isoaspartyl methyltransferase, insulin-like growth factor-1
