Mouse May Hold Clues to Human Ageing

A study by scientists at UCL (University College London) shows that mice lacking the insulin receptor substrate (IRS)-1 are more resistant to ageing than normal mice. The research adds to a growing body of work showing the importance of insulin signalling

University College London (UCL) scientists have just released the results of a study that demonstrate that that mice lacking the insulin receptor substrate (IRS)-1 are more resistant to ageing than normal mice. There is a growing body of work that is showing the importance of insulin signaling pathways as an ageing mechanism in mammals and potentially humans. This latest study adds to this work. Mice, referred to as knock-out mice, which were engineered to lack either insulin receptor substrate (IRS)-1 or -2, were studied. (IRS)-1 or -2 are proteins that are activated by insulin, a hormone that regulates glucose and fat metabolism, informing the body’s cells when the animal is well fed. Mice that lack IRS-1 had an average lifespan increase of 20 per cent when compared to normal mice. In female mice lacking IRS-1 this figure was even higher, averaging 30 per cent. The average life-span of a mouse is approximately 25 months, one of the IRS-1 deficient mice in this research lived for 38 months; this is 66 per cent longer than a normal mouse. The mice, that did not have IRS-1, in addition to living longer, experienced better health than the normal mice as they aged. These mice had brighter eyes, were more alert and were much healthier overall. Mice that lacked IRS-2 were shorter-lived than the normal mice and displayed signs of obesity and type 2 diabetes. Professor Dominic Withers, who works with the UCL Centre for Research on Ageing and is lead author of the study, said: “Our provisional results indicate that mice lacking IRS-1, particularly female mice, are more long-lived and show resistance to a range of markers that indicate ageing – including skin, bone, immune, and motor dysfunction. “What’s more, these improvements were seen despite the fact that removing IRS-1 made the mice resistant to insulin throughout their lives. These results suggest that IRS-1 is a pathway conserved by evolution that regulates the lifespan of mammals, and it may point to methods of potentially delaying ageing in humans. “We do not yet fully understand why lacking IRS-1 leads to longer life in mice. One possible explanation is that it makes them only mildly insulin resistant and that this, rather than having a negative effect on health, increases stress resistance, protects from damage and generally triggers other reactions in the body which extend life without compromising health.” Dr David Gems, another of the study’s authors, added: “Other research has shown that mutations in single genes in the insulin pathway can extend the life of animals. However, our research adds new information because it shows that not only does manipulation of this pathway regulate how long animals live, it also shows that these effects allow the mice to stay healthier for longer. In these animals we see delay in the onset of age-related illnesses such as osteoporosis, diabetes and immune dysfunction. Obviously it’s much harder to study these mechanisms in humans because our life expectancy is so much longer, but this study and our other work on ageing are laying crucial scientific groundwork.”