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Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

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.

Pubmed ID: 24793238


  • Villeda SA
  • Plambeck KE
  • Middeldorp J
  • Castellano JM
  • Mosher KI
  • Luo J
  • Smith LK
  • Bieri G
  • Lin K
  • Berdnik D
  • Wabl R
  • Udeochu J
  • Wheatley EG
  • Zou B
  • Simmons DA
  • Xie XS
  • Longo FM
  • Wyss-Coray T


Nature medicine

Publication Data

June 6, 2014

Associated Grants

  • Agency: NIA NIH HHS, Id: 1F31-AG034045-01
  • Agency: NIA NIH HHS, Id: AG03144
  • Agency: NIA NIH HHS, Id: AG045034
  • Agency: NIH HHS, Id: DP5 OD012178
  • Agency: NIH HHS, Id: DP5-OD1217
  • Agency: NICHD NIH HHS, Id: T32 HD007470
  • Agency: NIMH NIH HHS, Id: T32 MH020016
  • Agency: NCRR NIH HHS, Id: UL1-RR025744
  • Agency: NCATS NIH HHS, Id: UL1-TR000004

Mesh Terms

  • Age Factors
  • Aging
  • Animals
  • Blood Transfusion
  • Blotting, Western
  • Cell Line
  • Cognition Disorders
  • Cyclic AMP Response Element-Binding Protein
  • DNA Primers
  • Hippocampus
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Neuronal Plasticity
  • Parabiosis
  • Polymerase Chain Reaction