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

By Saul A. Villeda, Kristopher E Plambeck, J. Middeldorp, Joseph M. Castellano, Kira I. Mosher, Jian Luo, L. K. Smith, Gregor Bieri, Karin Lin, D. Berdnik and 8 more. Nature Medicine, 2014

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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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/c326e4261f7ebe508d29cdca9fbdf0f5a8d958e0

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Citations in the corpus

Inflammaging and 'Garb-aging'. (2017, background): “In animal models, strong evidence in favor of the propagation hypothesis of the ageing phenotype emerges from the heterochronic parabiosis experiments in rodents, where an aged phenotype was induced in young mice by connecting their circulatory system to that of old animals [71,72].”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “A study using a parabiosis mouse model comprising young and old mice indicates that blood from young mice may rejuvenate organs, where old mice showed improvements in synaptic plasticity and cognitive behavior [520].”
Measuring biological age using omics data (2022, background): “…studies 10–14 as well as multiple experimental paradigms, such as caloric restriction, heterochronic parabiosis and partial epigenetic reprogramming , have demonstrated that it is possible to manipulate ageing biology to ‘reju-venate’ physiological functioning in complex model organisms 15–28 .”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “In contrast, the systemic milieu from young animals can increase adult neurogenesis and improve synaptic plasticity as well as hippocampus-dependent cognitive performance, likely through the CREB pathway [103].”
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “Recent heterochronic parabiosis experiments demonstrated that introduction of young blood in old mice led to increased neurogenesis and dendritic spine density, and improved agerelated cognitive impairment, (Katsimpardi et al., 2014; Villeda et al., 2014).”
Role of ROS and RNS Sources in Physiological and Pathological Conditions (2016, result): “Recent findings from Villeda demonstrated a significant improvement in hippocampal learning exercises and contextual fear conditioning tasks when old mice were given plasma from young mice [411].”
The blood-brain barrier. (2015, background): “…between the blood and the CNS. Recently, systemic proteins have been im- plicated in regulating neurogenesis differently in youth and during aging (Villeda et al. 2011, 2014; Katsimpardi et al. 2014); however, it remains unclear whether this is because of specific transport, localized…”
Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. (2016, background): “Even though anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β, have been shown to improve the process of brain restoration following damage (Iadecola and Anrather, 2011), a comprehensive understanding of the endogenous protective mechanisms has yet to be demonstrated despite the findings th”