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ß2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis.
Smith, Lucas K; He, Yingbo; Park, Jeong-Soo; Bieri, Gregor; Snethlage, Cedric E; Lin, Karin; Gontier, Geraldine; Wabl, Rafael; Plambeck, Kristopher E; Udeochu, Joe; Wheatley, Elizabeth G; Bouchard, Jill; Eggel, Alexander; Narasimha, Ramya; Grant, Jacqueline L; Luo, Jian; Wyss-Coray, Tony; Villeda, Saul A.
Afiliação
  • Smith LK; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Biomedical Sciences Graduate Program, University of California San Francisco, Sa
  • He Y; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
  • Park JS; 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Department of Biochemistry, Dankook University College of Medicine, Cheonan, Korea.
  • Bieri G; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Department of Neurology and Neurological Sciences, Stanford University School of
  • Snethlage CE; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA.
  • Lin K; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Neuroscience Graduate Program, University of California San Francisco, San Franc
  • Gontier G; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA.
  • Wabl R; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
  • Plambeck KE; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA.
  • Udeochu J; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Biomedical Sciences Graduate Program, University of California San Francisco, Sa
  • Wheatley EG; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Developmental and Stem Cell Biology Graduate Program, University of California S
  • Bouchard J; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA.
  • Eggel A; Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Bern, Switzerland.
  • Narasimha R; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
  • Grant JL; 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
  • Luo J; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
  • Wyss-Coray T; 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA. [3] Center for Tissue Regeneration, Repair and Restoration, Veterans' Affairs
  • Villeda SA; 1] Department of Anatomy, University of California San Francisco, San Francisco, California, USA. [2] The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, USA. [3] Biomedical Sciences Graduate Program, University of California San Francisco, Sa
Nat Med ; 21(8): 932-7, 2015 Aug.
Article em En | MEDLINE | ID: mdl-26147761
ABSTRACT
Aging drives cognitive and regenerative impairments in the adult brain, increasing susceptibility to neurodegenerative disorders in healthy individuals. Experiments using heterochronic parabiosis, in which the circulatory systems of young and old animals are joined, indicate that circulating pro-aging factors in old blood drive aging phenotypes in the brain. Here we identify ß2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. B2M is elevated in the blood of aging humans and mice, and it is increased within the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically, or locally in the hippocampus, impairs hippocampal-dependent cognitive function and neurogenesis in young mice. The negative effects of B2M and heterochronic parabiosis are, in part, mitigated in the hippocampus of young transporter associated with antigen processing 1 (Tap1)-deficient mice with reduced cell surface expression of MHC I. The absence of endogenous B2M expression abrogates age-related cognitive decline and enhances neurogenesis in aged mice. Our data indicate that systemic B2M accumulation in aging blood promotes age-related cognitive dysfunction and impairs neurogenesis, in part via MHC I, suggesting that B2M may be targeted therapeutically in old age.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Microglobulina beta-2 / Cognição / Neurogênese Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Animals / Humans / Middle aged Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Microglobulina beta-2 / Cognição / Neurogênese Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Animals / Humans / Middle aged Idioma: En Ano de publicação: 2015 Tipo de documento: Article