An Exercise "sweet Spot" Reverses Cognitive Deficits of Aging by Growth-hormone-induced Neurogenesis

Overview

Journal iScience

Publisher Cell Press

Date 2021 Nov 11

PMID 34761193

Citations 14

Authors

Daniel G Blackmore

Frederik J Steyn

Alison Carlisle

Imogen OKeeffe

King-Year Vien

Xiaoqing Zhou

Odette Leiter

Dhanisha Jhaveri

Jana Vukovic

Michael J Waters

Perry F Bartlett

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Spatial transcriptomic clocks reveal cell proximity effects in brain ageing.

Sun E, Zhou O, Hauptschein M, Rappoport N, Xu L, Navarro Negredo P Nature. 2024; 638(8049):160-171.

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Spatiotemporal transcriptomic profiling and modeling of mouse brain at single-cell resolution reveals cell proximity effects of aging and rejuvenation.

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Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain.

Chauquet S, Willis E, Grice L, Harley S, Powell J, Wray N Aging Cell. 2024; 23(7):e14172.

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The effects of peripheral hormone responses to exercise on adult hippocampal neurogenesis.

Kraemer R, Kraemer B Front Endocrinol (Lausanne). 2023; 14:1202349.

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Cognitive performance during senescence in untreated congenital isolated GH deficiency.

Batista V, Kellner M, Salvatori R, Lisboa W, Faro A, Santos L Endocr Connect. 2023; 13(1).

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