title: Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.
abstract: As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.
authors.affiliation: 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 Francisco, California, USA. [4] Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA. [5] Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, California, USA. [6] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Saul A
authors.initials: SA
authors.lastname: Villeda
authors.affiliation: 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].
authors.forename: Kristopher E
authors.initials: KE
authors.lastname: Plambeck
authors.affiliation: 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2].
authors.forename: Jinte
authors.initials: J
authors.lastname: Middeldorp
authors.affiliation: 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2].
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Castellano
authors.affiliation: 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].
authors.forename: Kira I
authors.initials: KI
authors.lastname: Mosher
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jian
authors.identifier: 0000000220648467
authors.initials: J
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Lucas K
authors.initials: LK
authors.lastname: Smith
authors.affiliation: 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 Medicine, Stanford, California, USA. [4] Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bieri
authors.affiliation: 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 Francisco, California, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berdnik
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Wabl
authors.affiliation: 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, San Francisco, California, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Udeochu
authors.affiliation: 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 San Francisco, San Francisco, California, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Wheatley
authors.affiliation: AfaSci Research Laboratory, Redwood City, California, USA.
authors.forename: Bende
authors.identifier: 0000000229073102
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Simmons
authors.affiliation: AfaSci Research Laboratory, Redwood City, California, USA.
authors.forename: Xinmin S
authors.initials: XS
authors.lastname: Xie
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Longo
authors.affiliation: 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, VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001803:Blood Transfusion / Q000379:methods*; D015153:Blotting, Western; D002460:Cell Line; D003072:Cognition Disorders / Q000503:physiopathology* / Q000628:therapy*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009473:Neuronal Plasticity / Q000502:physiology*; D010227:Parabiosis / Q000379:methods; D016133:Polymerase Chain Reaction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers