TY - JOUR
T1 - Siglec receptors impact mammalian lifespan by modulating oxidative stress
AU - Schwarz, Flavio
AU - Pearce, Oliver M.T.
AU - Wang, Xiaoxia
AU - Samraj, Annie N.
AU - Läubli, Heinz
AU - Garcia, Javier O.
AU - Lin, Hongqiao
AU - Fu, Xiaoming
AU - Garcia-Bingman, Andrea
AU - Secrest, Patrick
AU - Romanoski, Casey E.
AU - Heyser, Charles
AU - Glass, Christopher K.
AU - Hazen, Stanley L.
AU - Varki, Nissi
AU - Varki, Ajit
AU - Gagneux, Pascal
N1 - Publisher Copyright:
© 2015, Schwarz et al.
PY - 2015/4/7
Y1 - 2015/4/7
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.06184
DO - 10.7554/eLife.06184
M3 - Article
C2 - 25846707
AN - SCOPUS:84979852569
VL - 2015
JO - eLife
JF - eLife
SN - 2050-084X
IS - 4
M1 - e06184
ER -