The ageing systemic milieu negatively regulates neurogenesis and cognitive function.

Authors: Villeda SA; Luo J; Mosher KI; Zou B; Britschgi M; Bieri G; Stan TM; Fainberg N; Ding Z; Eggel A; Lucin KM; Czirr E; Park JS; Couillard-Després S; Aigner L; Li G; Peskind ER; Kaye JA; Quinn JF; Galasko DR; Xie XS; Rando TA; Wyss-Coray T

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.

Keywords: Aging; Animals; Chemokine CCL11/blood/cerebrospinal fluid/metabolism/pharmacology; Chemokines/*blood/cerebrospinal fluid/*metabolism; Female; Learning/drug effects/*physiology; Learning Disorders/blood/cerebrospinal fluid/physiopathology; Male; Memory Disorders/blood/cerebrospinal fluid/physiopathology; Mice; Mice, Inbred C57BL; Neurogenesis/drug effects/*physiology; Parabiosis; Plasma/chemistry; Time Factors
Journal: Nature
Volume: 477
Issue: 7362
Pages: 90-4
Date: Sept. 3, 2011
PMID: 21886162
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Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477: 90-4.

Lifespan Factors:
  • CCL11 chemokine (C-C motif) ligand 11
  • CCL11 chemokine (C-C motif) ligand 11
  • CCL2 chemokine (C-C motif) ligand 2

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