An exercise “sweet spot” reverses cognitive deficits of aging by growth-hormone-induced neurogenesis
Daniel G. Blackmore,
Frederik J. Steyn,
Alison Carlisle,
Imogen O’Keeffe,
King-Year Vien,
Xiaoqing Zhou,
Odette Leiter,
Dhanisha Jhaveri,
Jana Vukovic,
Michael J. Waters,
Perry F. Bartlett
Affiliations
Daniel G. Blackmore
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Frederik J. Steyn
Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia
Alison Carlisle
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Imogen O’Keeffe
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
King-Year Vien
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Xiaoqing Zhou
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Odette Leiter
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Dhanisha Jhaveri
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Mater Research Institute, The University of Queensland, Brisbane, QLD 4072, Australia
Jana Vukovic
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
Michael J. Waters
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
Perry F. Bartlett
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Corresponding author
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.
