The aging systemic milieu negatively regulates neurogenesis and cognitive function

By Saul A. Villeda, Jian Luo, Kira I. Mosher, Bende Zou, Markus Britschgi, Gregor Bieri, Trisha M. Stan, Nina Fainberg, Zhaoqing Ding, A. Eggel and 13 more. Nature, 2011

1,032 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/bd5427deef432e94daabfe126560e408e6f20241

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Guido Kroemer
2. A. Wagers

In Developmental Neuroscience

1. Thuc M. Le

In Neurology

1. Guido Kroemer
2. Linda Partridge

Citations in the corpus

• The hallmarks of aging. (2013, background): “Furthermore, parabiosis experiments have demonstrated that the decline in neural and muscle stem cell function in old mice can be reversed by systemic factors from young mice (Conboy et al., 2005; Villeda et al., 2011).”
• Growth Differentiation Factor 11 is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy (2013, positive): “Conversely, exposing a young mouse to an old systemic environment can inhibit myogenesis (Brack et al., 2007) and neurogenesis (Villeda et al., 2011) in the young mouse.”
• Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal (2014, background): “Although some extrinsic cellular factors such as an inflammatory microenvironment promote aging (Ergen et al., 2012; Villeda et al., 2011), these impact the hematopoietic stem cells (HSCs), causing cellintrinsic changes that affect the generation of a balanced supply of differentiated blood…”