Genetically altered organisms lacking an insulin receptor live longer. The related processes of insulin and growth hormone signaling are one of the better-studied areas of biochemistry in the context of aging as a result, largely focused on loss of function mutants and why they are long-lived. Here, however, researchers investigate the normal function of insulin receptors, attempting to expand our understanding of the way in which natural variations in longevity are determined by the operation of cellular metabolism.
Early in evolution, sugar intake and the regulation of life span were linked with each other. The hormone insulin is crucial here. It reduces blood sugar levels by binding to its receptor on the cell surface. However, many processes for stress management and survival are shut down at the same time. When there is a good supply of food, they appear unnecessary to the organism, although this reduces life expectancy over the long term. The insulin receptor thus acts like a brake on life expectancy. Genetically altered laboratory animals in which the insulin receptor no longer functions actually live much longer than normal. But how is the insulin receptor normally kept in check in our cells and tissue? A recent study answers this fundamental question.
The team of researchers shows that the protein CHIP plays a crucial role here. It acts like a disposal helper, in that it supplies the insulin receptor to the cellular breakdown and recycling systems by affixing the molecule ubiquitin onto the receptor. The life expectancy brake is thus released and CHIP unfurls anti-aging activity. CHIP fulfils this function in nematodes, as well as in fruit flies and in humans. The findings were initially very surprising, as CHIP had so far been associated with completely different breakdown processes. Specifically, CHIP also disposes of faulty and damaged proteins, which increasingly occur at an older age and the accumulation of which leads to dementia and muscle weakness. The researchers actually recreated such degenerative illnesses in the nematode and in human cells and observed that there was no longer enough CHIP available to break down the insulin receptor. Premature aging is the result.
Can the dream of a fountain of youth be made a reality and life extended in that researchers encourage cells to form more CHIP? Unfortunately, it’s not that easy. When there is too much CHIP, undamaged proteins are also recycled and the organism is weakened. However, the researchers are already looking for mechanisms that control CHIP when breaking down the insulin receptor and that could one day also be used for new treatments.