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Central regulation of food intake in ageing

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Energy homeostasis and fuel metabolism undergo significant modifications in the course of ageing. During the second half of life many humans increase their body mass and develop glucose intolerance that may lead to obesity and type 2 diabetes. However, many old people suffer from being underweight, and this "anorexia of elderly" may seriously compromise their health under certain circumstances. Experimental studies into the causes of ageing-related impairments of food intake regulation were performed mainly on rat, and to some extent, on non-human primates. It was found that the expression of NPY, the most potent orexigenic peptide, and of NPY receptors, is highly suppressed in the hypothalamus of old rats. Moreover, the increase of NPY mRNA after fasting was severely blunted in old as compared to young rats. Similar reductions, although of lower magnitude, were reported for other hypothalamic orexigenic compounds such as, AgRP and orexins. Interestingly, ageing does not significantly alter hypothalamic mRNA levels of important anorexigens such as CART and aMSH. The presented findings suggest that, at least in rodents, ageing is associated with the general down-regulation of hypothalamic peptides that stimulate food intake and unchanged expression of anorexigenic peptides. This situation may be responsible for the decreased appetite drive in senescent animals and loss of weight at the end-of-life period. If similar changes of the central control of food intake underly „anorexia of ageing“ observed in some elderly, it is possible that therapeutic intervention at this regulatory level may be possible in the future.
The impairment of homeostatic mechanisms in ageing becomes often apparent upon physiological or pathological stimulation. We have previously shown that fasting and refeeding revealed the existence of age-related changes of carbohydrate and lipid metabolism. Because fuel metabolism is partially controlled by corticosteroids we decided to determine the effects of refeeding on adrenal gland morphometry, ACTH, and corticosterone serum levels in young (5 mo) and (20 mo) old male Wistar rats. Fasting for 48 h did not change serum ACTH and corticosterone in both age groups. ACTH level did not change after 24 h of refeeding in young and old rats. However, in old, but not young animals, refeeding resulted in the decrease of corticosterone serum concentration. The relative weight of adrenal gland (% of body weight) did not change significantly with age (p=0.05). Fasting for 48 h induced in old rats but not in young ones increase of relative adrenal weight, and the volume of the reticular zone. Refeeding reduced adrenal volume, fascicular zone and reticular zone. Refeeding for 24 h decreased the total volume of adrenal gland of old rats due to a decline of the volumes of fascicular and reticular zones. In young rats refeeding reduced the volume of reticular zone. It is concluded that refeeding revealed ageing-dependent decline in the secretion of corticosterone, the key hormone of prolonged stress response.
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