Life‐long food restriction and volunt1ary exercise reverses age‐related changes in hypothalamic and adrenal medullary tyrosine hydroxylase biosynthesis

Abstract

Tyrosine hydroxylase (TH) biosynthesis increases in adrenal medulla (AM) and decreases in the hypothalamus with age. We examined if food restriction or voluntary exercise prevents these age-related alterations. 10 wk-old Fisher-344 rats were assigned to: sedentary; sedentary + 8% food restriction; or 8% food restriction + wheel running. Rats were euthanized at 6 or 24 months of age. TH expression and levels of AP-1 and CREB transcription factors were analysed in the AM and hypothalamus. TH expression was more then 4 times higher in the AM of 24 month-old rats compared to 6 month-old (p<0.01). This increase in TH was reduced by 30% with food restriction (p<0.05), but voluntary wheel running had no additional effect over food restriction. In the hypothalamus, TH expression decreased by 60% with age (p<0.01), but food restriction completely prevented this age-related decrease in TH. Voluntary exercise, however, had no additional effect over food restriction. Changes in AP-1 and CREB levels did not parallel those of TH. Both AP-1 and CREB were significantly lower in the 24 compared to 6 month-old rats, and food restriction or wheel running had no effect on AP-1 and CREB levels. In conclusion, TH expression increases in the AM and decreases in the hypothalamus with age, and food restriction reduces these age-related changes. Voluntary wheel running, however, has no additional effect above that of 8% food restriction. Supported by the Medical Research Service of the Department of VA and NIA.