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Siglec receptors impact mammalian lifespan by modulating oxidative stress.

  • Author(s): Schwarz, Flavio
  • Pearce, Oliver MT
  • Wang, Xiaoxia
  • Samraj, Annie N
  • Läubli, Heinz
  • Garcia, Javier O
  • Lin, Hongqiao
  • Fu, Xiaoming
  • Garcia-Bingman, Andrea
  • Secrest, Patrick
  • Romanoski, Casey E
  • Heyser, Charles
  • Glass, Christopher K
  • Hazen, Stanley L
  • Varki, Nissi
  • Varki, Ajit
  • Gagneux, Pascal
  • et al.
Abstract

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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