Siglec receptors impact mammalian lifespan by modulating oxidative stress.
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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.
AuthorsSchwarz, F; Pearce, OMT; Wang, X; Samraj, AN; Läubli, H; Garcia, JO; Lin, H; Fu, X; Garcia-Bingman, A; Secrest, P; Romanoski, CE; Heyser, C; Glass, CK; Hazen, SL; Varki, N; Varki, A; Gagneux, P
- College Publications