Siglec receptors impact mammalian lifespan by modulating oxidative stress

Flavio Schwarz, Oliver M.T. Pearce, Xiaoxia Wang, Annie N. Samraj, Heinz Läubli, Javier O. Garcia, Hongqiao Lin, Xiaoming Fu, Andrea Garcia-Bingman, Patrick Secrest, Casey E. Romanoski, Charles Heyser, Christopher K. Glass, Stanley L. Hazen, Nissi Varki, Ajit Varki, Pascal Gagneux

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Article numbere06184
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Apr 7 2015
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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