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Efficacy of Ghrelin as a Therapeutic Approach for Age-Related Physiological Changes

Ghrelin Research Project, Translational Research Center (H.A., H.I., T.A.), Kyoto University Hospital, and Department of Endocrinology and Metabolism (G.Y., K.N.), Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; and Department of Biochemistry (K.K.), National Cardiovascular Center Research Institute, Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Hiroyuki Ariyasu, Ghrelin Research Project, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan. E-mail: ariyasu{at}kuhp.kyoto-u.ac.jp.

Aging is associated with decreases in food intake and GH secretion, termed the anorexia of aging and somatopause, respectively. The mechanisms underlying these phenomena are not fully understood. Although many approaches have attempted to improve these age-related physiological changes, none have achieved satisfactory results. Ghrelin, a 28-amino-acid acylated peptide, was identified as an endogenous ligand for the GH secretagogue receptor. Ghrelin stimulates GH secretion and food intake in animals and humans. Previous studies have demonstrated that the mean plasma concentrations of ghrelin in normal-weight elderly people were lower than those in younger people. We hypothesized that ghrelin administration might improve the metabolic and physiological changes that accompany the anorexia of aging and somatopause. First, 75-wk-old mice fasted for 72 h, after which they resumed feeding with sc administration of ghrelin (360 µg/kg) twice daily for 4 d. Multiple administrations of ghrelin after a 72-h fast increased food intake and hastened body weight recovery with a high lean body mass ratio. Next, 50-wk-old mice were sc injected with rat ghrelin (40 µg/kg) twice weekly from 50–80 wk of age. Long-term administration of ghrelin kept aged mice with low body weight and low adiposity. These results suggest that ghrelin might be a novel approach for the therapy of age-related metabolic and physiological changes.

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