%0 Journal Article %J Elife %D 2015 %T Siglec receptors impact mammalian lifespan by modulating oxidative stress. %A Schwarz, F %A Pearce, OM %A Wang, X %A Samraj, AN %A Laubli, H %A Garcia, JO %A Lin, H %A Fu, X %A Garcia-Bingman, A %A Secrest, P %A Romanoski, CE %A Heyser, C %A Glass, CK %A Hazen, SL %A Nissi M Varki %A Ajit Varki %A Gagneux, P %X

Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan.

%B Elife %V 4 %@ 2050-084X %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/25846707 %M 25846707