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. 2007 Aug;42(8):745-52.
doi: 10.1016/j.exger.2007.04.007. Epub 2007 Apr 24.

Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus

Benedek Erdös  1 , Christopher S Broxson, Tessa Landa, Philip J Scarpace, Christiaan Leeuwenburgh, Yi Zhang, Nihal Tümer
Affiliations

Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus

Benedek Erdös et al. Exp Gerontol. 2007 Aug.

Abstract

We examined if life-long mild caloric restriction (CR) alone or with voluntary exercise prevents the age-related changes in catecholamine biosynthetic enzyme levels in the adrenal medulla and hypothalamus. Ten-week-old Fisher-344 rats were assigned to: sedentary; sedentary+8% CR; or 8% CR+wheel running. Rats were euthanized at 6 or 24 months of age. Tyrosine hydroxylase (TH) mRNA expression was 4.4-fold higher in the adrenal medullae and 60% lower in the hypothalamus of old sedentary rats compared to young (p<0.01). Life-long CR reduced the age-related increase in adrenomedullary TH by 50% (p<0.05), and completely reversed the changes in hypothalamic TH. Voluntary exercise, however, had no additional effect over CR. Since angiotensin II is involved in the regulation of catecholamine biosynthesis, we examined the expressions of angiotensin II receptor subtypes in the adrenal medulla. AT(1) protein levels were 2.8-fold higher in the old animals compared to young (p<0.01), and while AT(1) levels were unaffected by CR alone, CR+wheel running decreased AT(1) levels by 50% (p<0.01). AT(2) levels did not change with age, however CR+wheel running increased its level by 42% (p<0.05). These data indicate that a small decrease in daily food intake can avert age-related changes in catecholamine biosynthetic enzyme levels in the adrenal medulla and hypothalamus, possibly through affecting angiotensin II signaling.

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Figures

Fig. 1
Fig. 1
Changes in TH mRNA (panel A) and protein (panel B) levels in the adrenal medulla with age and in response to caloric restriction (CR) and exercise (Ex) as measured with Northern and Western blot analysis and expressed in percentage of the 6-month-old control group. TH mRNA and protein levels increased significantly with age, but CR and CR plus exercise reduced the age-related TH upregulation. *p<0.05, **p<0.01 vs. 6-month-old control. #p<0.05 vs. 24-month-old control.
Fig. 2
Fig. 2
Changes in DβH mRNA levels in the adrenal medulla with age and in response to caloric restriction (CR) and exercise (Ex) as measured with Northern blot analysis and expressed as percentage of DβH mRNA in the 6-month-old control group. DβH mRNA increased significantly with age, but CR and CR plus exercise prevented the age-related DβH upregulation. *p<0.05 vs. 6-month-old control. #p<0.05 vs. 24-month-old control.
Fig. 3
Fig. 3
Changes in AT1 (panel A) and AT2 (panel B) receptor protein levels in the adrenal medulla with age and in response to caloric restriction (CR) and exercise (Ex) as measured with Western blot analysis and expressed in percentage of the 6-month-old control group. AT1 protein increased significantly with age. 8% CR alone had no effect on AT1 levels, however CR in combination with voluntary wheel running prevented the age-related upregulation of AT1. AT2 protein levels did not change with age. However, 8% CR alone or in combination with exercise increased the levels of this receptor subtype. **p<0.01 vs. 6-month-old control. #p<0.05, ##p<0.01 vs. 24-month-old control.
Fig. 4
Fig. 4
Changes in TH (panel A) and DβH (panel B) mRNA levels in the hypothalamus with age and in response to caloric restriction (CR) and exercise (Ex) as measured with Northern blot analysis and expressed in percentage of the 6-month-old control group. Both TH and DβH mRNA levels decreased significantly with age, but CR and CR plus wheel running prevented the age-related TH downregulation. **p<0.01 vs. 6-month-old control. ##p<0.01 vs. 24-month-old control.
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