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The ageing systemic milieu negatively regulates neurogenesis and cognitive function.
Saul A Villeda1, Jian Luo, Kira I Mosher
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|September 3, 2011
Summary
Aging impairs brain stem cell activity and memory. Blood factors from old mice reduce neurogenesis and cognitive function in young mice, identifying CCL11 as a key molecule. This suggests blood-borne factors contribute to age-related cognitive decline.
Area of Science:
- Neuroscience
- Aging Research
- Stem Cell Biology
Background:
- Aging leads to decreased neural stem/progenitor cells and neurogenesis in the central nervous system.
- Cognitive functions decline with age, but can be improved by factors like exercise.
- The role of systemic factors in age-related neurogenesis decline is not fully understood.
Purpose of the Study:
- To investigate the impact of systemic, blood-borne factors on adult neurogenesis and cognitive function in an age-dependent manner.
- To identify specific molecules in the blood that influence neurogenesis and learning during aging.
Main Methods:
- Heterochronic parabiosis in mice to study the effects of young and old systemic environments.
- Assessment of synaptic plasticity, contextual fear conditioning, and spatial learning and memory.
- Measurement of plasma and cerebrospinal fluid chemokine levels, specifically CCL11 (eotaxin).
- In vivo manipulation of CCL11 levels in young mice.
Main Results:
- Exposure to an old systemic environment or old mouse plasma reduced neurogenesis, synaptic plasticity, and cognitive performance in young mice.
- Plasma levels of the chemokine CCL11 correlated with reduced neurogenesis in parabionts and aged mice.
- CCL11 levels were elevated in the plasma and cerebrospinal fluid of healthy aging humans.
- Increased peripheral CCL11 in young mice decreased neurogenesis and impaired learning and memory.
Conclusions:
- Blood-borne factors in the systemic milieu can inhibit adult neurogenesis in an age-dependent manner.
- The chemokine CCL11 is identified as a key blood-borne factor contributing to age-related decline in neurogenesis and cognitive function.
- These findings suggest that targeting blood-borne factors may offer therapeutic strategies for age-related cognitive impairments.
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