iScience
Volume 24, Issue 11, 19 November 2021, 103275
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Article
An exercise “sweet spot” reverses cognitive deficits of aging by growth-hormone-induced neurogenesis

https://doi.org/10.1016/j.isci.2021.103275Get rights and content
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Highlights

  • Only specific periods of exercise restores spatial learning in aged mice

  • Increased growth hormone (GH) mediates improved learning by activating neurogenesis

  • Neurogenesis is required for exercise-mediated improvement in learning

  • Identification of mechanisms regulating GH-mediated improvements in learning

Summary

Hippocampal function is critical for spatial and contextual learning, and its decline with age contributes to cognitive impairment. Exercise can improve hippocampal function, however, the amount of exercise and mechanisms mediating improvement remain largely unknown. Here, we show exercise reverses learning deficits in aged (24 months) female mice but only when it occurs for a specific duration, with longer or shorter periods proving ineffective. A spike in the levels of growth hormone (GH) and a corresponding increase in neurogenesis during this sweet spot mediate this effect because blocking GH receptor with a competitive antagonist or depleting newborn neurons abrogates the exercise-induced cognitive improvement. Moreover, raising GH levels with GH-releasing hormone agonist improved cognition in nonrunners. We show that GH stimulates neural precursors directly, indicating the link between raised GH and neurogenesis is the basis for the substantially improved learning in aged animals.

Subject areas

Age
Endocrine system physiology
Neuroscience

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report the original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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