Siglec receptors impact mammalian lifespan by modulating oxidative stress

Flavio Schwarz; Oliver MT 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

doi:10.7554/eLife.06184

eLife (Apr 2015)

Siglec receptors impact mammalian lifespan by modulating oxidative stress

Flavio Schwarz,
Oliver MT 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

Affiliations

Flavio Schwarz: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Oliver MT Pearce: ORCiD; Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Xiaoxia Wang: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Annie N Samraj: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Heinz Läubli: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Javier O Garcia: Department of Psychology, University of California, San Diego, San Diego, United States
Hongqiao Lin: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States
Xiaoming Fu: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States
Andrea Garcia-Bingman: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Patrick Secrest: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Casey E Romanoski: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Charles Heyser: Department of Neurosciences, University of California, San Diego, San Diego, United States
Christopher K Glass: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Stanley L Hazen: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States
Nissi Varki: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Pathology, Division of Comparative Pathology and Medicine, University of California, San Diego, San Diego, United States
Ajit Varki: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Medicine, University of California, San Diego, San Diego, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
Pascal Gagneux: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States; Department of Pathology, Division of Comparative Pathology and Medicine, University of California, San Diego, San Diego, United States

DOI: https://doi.org/10.7554/eLife.06184
Journal volume & issue: Vol. 4

Abstract

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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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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