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

Abstract

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 microg/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 microg/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.

Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy

“…Also, the plasma acylated ghrelin concentration was shown to be significantly increased after rikkunshito treatment [15]. Ghrelin stimulates food intake [9] and triggers a positive energy balance through a central mechanism involving hypothalamic neuropeptides [9][10][11][12]. Taken together, these reports suggest that the induction of ghrelin could be In the present study, however, the administration of rikkunshito did not increase the ghrelin concentration per se.…”

“…During metabolic processing, a fraction of desacyl-ghrelin is acylated in position 3 (serine) to form variants of acyl-ghrelin. Acyl-ghrelin displays dosedependent GH-releasing activity [8,9], stimulates food intake, triggers a positive energy balance [10][11][12], and is considered to be the active form of ghrelin [11,[35][36][37]. Actually, several components of rikkunshito demonstrate inhibitory activity against ghrelin desacylating enzymes [38].…”

“…Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, displays dose-dependent GH-releasing activity [8,9]. Ghrelin, which is predominantly secreted by gastric endocrine cells, stimulates food intake and triggers a positive energy balance through a central mechanism involving hypothalamic neuropeptides [10][11][12]. In our previous study, we reported that intravenous administration of ghrelin enhanced oral feeding and was effective against weight loss after total gastrectomy [13] and esophagectomy [14] in cancer patients.…”

Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats

“…Moreover, ghrelin decreases energy expenditure in rodents, thus increasing adiposity and facilitating weight gain (Tschop et al, 2000). Ghrelin concentrations have been reported to be decreased in elderly people (Rigamonti et al, 2002;Sturm et al, 2003), and old rats failed to upregulate the levels of circulating ghrelin during food deprivation (Wolden-Hanson et al, 2004), indicating that inadequate ghrelin response might contribute to the anorexia of aging (Kmiec, 2010 endogenous ghrelin significantly contributes to the regulation of food intake in humans (Lippl et al, 2012), exogenous administration of ghrelin or its receptor agonists has been suggested as a potential therapeutic approach for anorexia and other age-related physiological changes (Ariyasu et al, 2008;Muccioli et al, 2002). Moreover, this approach has also been considered in the treatment of cachexia associated with chronic illnesses, including cancer, heart failure, chronic kidney disease, and acquired immunodeficiency syndrome (DeBoer, 2008;Deboer et al, 2008;DeBoer et al, 2007).…”

Growth Hormone Secretagogues Exert Differential Effects on Skeletal Muscle Calcium Homeostasis in Male Rats Depending on the Peptidyl/Nonpeptidyl Structure

“…A growing number of studies highlight the possible therapeutic effects of these molecules in diseases associated with muscle wasting, including anorexia nervosa, chronic obstructive pulmonary disease (COPD), functional dyspepsia and chronic heart failure (4 -6), despite the necessity to assess the long-term efficacy and safety of GHSs therapies. Furthermore, the use of GHSs has been proposed to either prevent or treat the effects of aging and disuse on skeletal muscles (7)(8)(9)(10).…”