Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 375

Ghrelin stimulates feeding and growth hormone release. It is present in the hypothalamus, but the main site of production is the gastric mucosa.³⁰ Circulating ghrelin concentrations increase with fasting and diet‐induced weight loss in obese subjects and are elevated in underweight, undernourished young and older subjects. In contrast, circulating concentrations decrease after food ingestion, particularly fat and carbohydrate, and are reduced in obese people. These changes are consistent with compensatory responses to, rather than causes of, these altered nutritional states. It therefore seems unlikely that reduced ghrelin activity contributes significantly to anorexia and weight loss in markedly undernourished older subjects. Nevertheless, the effects of ageing and undernutrition on sensitivity to ghrelin have not been reported, and ghrelin resistance may occur in these states. In support of this, older subjects are less sensitive to the growth hormone (GH)‐releasing effects of intravenous ghrelin (i.v. ghrelin) than young adults.⁵³ The effect of healthy ageing on circulating ghrelin concentrations has not yet been clarified. A possible rationale for a decline in ghrelin levels with age, particularly in men, is the positive association between circulating testosterone and ghrelin concentrations and the increase in plasma ghrelin concentrations that occurs in hypogonadal men in response to testosterone therapy.⁵⁴ As normal ageing is accompanied by reductions in circulating androgen levels (see the following section), this might have the effect of reducing ghrelin concentrations and thus food intake. One study found a rise in plasma ghrelin concentrations with increasing age, but there was no relationship with age per se when a multivariate analysis was performed, and the study did not include subjects older than 64.⁵⁵ Two small studies have reported circulating ghrelin concentrations 20%⁵⁶ and 35%⁵⁷ lower in healthy older adults (69–87 and 67–91 years, respectively) than young adults, the latter reduction being statistically significant. However, increasing body fat, as indicated by BMI, is associated with decreasing ghrelin concentrations, and the older subjects had higher BMIs than the young subjects in both studies. Neither study included detailed body composition analysis, so the lower ghrelin levels in older subjects may have been because of differences in body composition. Another study found no difference in fasting and postprandial serum ghrelin concentrations between healthy older (mean age 78) and young adults. On balance, the effect of healthy ageing on circulating ghrelin concentrations has not yet been clarified but is probably minimal.⁵⁸