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 aging1,2. 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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
We thank A. Eggel, K. Lucin and N. Woodling for critical review and advice, and D. Jing and F. Lee (Cornell University) for Golgi stain reagents. This work was funded by California Institute for Regenerative Medicine (CIRM) fellowships (K.E.P. and K.L.), a Netherlands Organization for Scientific Research (NWO) Rubicon fellowship (J.M.), a Child Health Research Institute fellowship (Stanford National Institutes of Health (NIH)/National Center for Research Resources CTSA-UL1-RR025744, J.M.C.), a Jane Coffin Childs fellowship (J.M.C.), National Science Foundation fellowships (K.I.M. and J.U.), a National Research Service Award fellowship (1F31-AG034045-01, S.A.V.), anonymous (T.W.-C.), Veterans Affairs (T.W.-C.), the National Institute on Aging (AG045034, AG03144, T.W.-C.), CIRM (T.W.-C.), the University of California San Francisco (UCSF) Program for Breakthrough Biomedical Research, the Sandler Foundation (S.A.V.), the UCSF Clinical and Translational Science Institute (UL1-TR000004, S.A.V.) and an NIH Director's Independence Award (DP5-OD12178, S.A.V.).
Supplementary Figures 1–12 and Supplementary Table 1
About this article
Nature Reviews Neuroscience (2018)