title: Siglec receptors impact mammalian lifespan by modulating oxidative stress.
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.
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Flavio
authors.initials: F
authors.lastname: Schwarz
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Oliver M T
authors.identifier: http://orcid.org/0000-0003-3953-1629
authors.initials: OM
authors.lastname: Pearce
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Annie N
authors.initials: AN
authors.lastname: Samraj
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Heinz
authors.initials: H
authors.lastname: Läubli
authors.affiliation: Department of Psychology, University of California, San Diego, San Diego, United States.
authors.forename: Javier O
authors.initials: JO
authors.lastname: Garcia
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States.
authors.forename: Hongqiao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Fu
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Garcia-Bingman
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Secrest
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Casey E
authors.initials: CE
authors.lastname: Romanoski
authors.affiliation: Department of Neurosciences, University of California, San Diego, San Diego, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Heyser
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, United States.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.affiliation: Glycobiology Research and Training Center, University of California, San Diego, San Diego, United States.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gagneux
mesh_terms: D000818:Animals; D001835:Body Weight; D006706:Homeostasis; D056747:Immunomodulation; D008136:Longevity; D008297:Male; D008322:Mammals / Q000235:genetics / Q000502:physiology*; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D018384:Oxidative Stress; D010641:Phenotype; D010802:Phylogeny; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000172:deficiency / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C092488:sialic acid receptor
keywords: Siglec; aging; evolutionary biology; genomics; immunology; inflammation; mouse; reactive oxygen species
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