Siglec receptors impact mammalian lifespan by modulating oxidative stress.

As we get older, we are more likely to become frail, be less mobile and develop heart disease, diabetes, and other age-related diseases. This is partly due to damage to tissues and organs that accumulates over the course of our lifetime. How quickly we age is controlled both by our genetics and by the environment we live in. It is thought that damage to DNA, proteins, and other molecules in the body caused by chemically active molecules called reactive oxygen species (ROS) can influence aging. ROS are produced during respiration, immune responses, and other important processes in cells, but in excessive amounts they can be extremely harmful. To avoid damage to DNA and other important molecules, cells have several ways to control the levels of ROS. One of the other hallmarks of aging is the development of chronic inflammation in tissues around the body, which is partly triggered by the immune system in response to cell damage. A group of genes called the CD33rSIGLEC genes are involved in controlling inflammation. The genomes of different mammal species carry different numbers of these genes, but it is not clear whether this alters the aging process in these animals. In this study, Schwarz et al. investigated whether the CD33rSIGLEC genes influence the lifespans of mammals. Species with a higher number of CD33rSIGLEC genes generally have a longer lifespan than those with fewer of these genes. Mice that were missing one of these genes and were subjected to inflammation early in life showed signs of accelerated aging and had shortened lifespans compared with normal mice. As predicted, these mice also had higher levels of ROS, which led to a greater amount of damage to the DNA and other molecules in their bodies. Schwarz et al.'s findings suggest that the CD33rSIGLECs co-evolved in mammals to help control the levels of ROS during inflammation, thereby reducing the damage to cells and extending the lifespan of the animals. Given that individual humans have different numbers of working CD33rSIGLEC genes, it would be interesting to see if this influences human lifespan.