Siglecs are a family of sialic acid–binding receptors with generally immunoinhibitory functions. In eLife, Gagneux et al. investigate whether the substantial variability in Siglec members in both expression and type contributes to the differences between species in aging. In many, varied mammalian species, the authors find a positive correlation between the number of Siglec-encoding genes and species lifespan. Furthermore, mice deficient in one member, Siglec-E, have a significantly shorter lifespan. Siglec-E-deficient mice have no overt alteration in phenotype other than accelerated cognitive and physical decline. Siglec-E is expressed mainly by phagocytes, and Siglec-E-deficient mice have enhanced production of reactive oxygen species (ROS) and immunological activation in the liver. This enhancement in ROS is correlated with increased signs of DNA damage, as well as oxidation of lipids and proteins, classic signs of aging. These data suggest that if it is not 'buffered' appropriately, activation of the innate immune system may lead at least in part to more rapid aging.

eLife (7 April 2015) doi:10.7554/eLife.06184