The ageing systemic milieu negatively regulates neurogenesis and cognitive function

Saul A. Villeda, Jian Luo, Kira I. Mosher, Bende Zou, Markus Britschgi, Gregor Bieri, Trisha M. Stan, Nina Fainberg, Zhaoqing Ding, Alexander Eggel, Kurt M. Lucin, Eva Czirr, Jeong Soo Park, Sebastien Couillard-Després, Ludwig Aigner, Ge Li, Elaine R. Peskind, Jeffrey A. Kaye, Joseph F. Quinn, Douglas R. GalaskoXinmin S. Xie, Thomas A. Rando, Tony Wyss-Coray

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822 Scopus citations

Abstract

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines-including CCL11 (also known as eotaxin)-the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalNature
Volume477
Issue number7362
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

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    Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., Stan, T. M., Fainberg, N., Ding, Z., Eggel, A., Lucin, K. M., Czirr, E., Park, J. S., Couillard-Després, S., Aigner, L., Li, G., Peskind, E. R., Kaye, J. A., Quinn, J. F., ... Wyss-Coray, T. (2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477(7362), 90-96. https://doi.org/10.1038/nature10357