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Calorie restriction delays age-dependent loss in androgen responsiveness of the rat liver
B Chatterjee1, G Fernandes, B P Yu
1Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Abstract:
We have shown that restricted calorie intake retards age-associated loss in androgen responsiveness of the rat liver. Sustained androgen receptivity delays age-dependent decline in the synthesis of the androgen-inducible alpha 2u globulin and derepression of the androgen-repressible senescence marker protein (SMP-2). Quantitation of mRNAs for alpha 2u globulin and SMP-2 in the liver of animals of various ages maintained on either ad libitum or restricted diets revealed that, although the 27-month-old ad libitum-fed rat had only 5% as much alpha 2u mRNA as the 6-month-old rat, the mRNA level was as high as 45% in the 27-month-old food-restricted rat. Conversely, the 27-month-old food-restricted rat had a much reduced amount (45%) of SMP-2 mRNA compared to the age-matched control that was allowed unlimited access to food. Furthermore, we have correlated the effect of dietary restriction on age-dependent changes in specific gene expression with the hepatic level of the immunoreactive cytoplasmic androgen-binding (CAB) protein. We observed that senescence in the male causes a substantial decrease in the circulating level of testosterone. However, dietary restriction does not retard the rate of decline in the plasma level of the male hormone during aging. These results indicate that age-dependent changes in the expression of androgen-responsive genes (alpha 2u globulin and SMP-2) reflect changing androgen sensitivity and that food restriction may directly influence the androgen receptivity of the liver.
Insights
Restricted calorie intake maintains liver androgen sensitivity in aging rats, preserving key gene expression. This dietary strategy delays age-related declines in specific protein synthesis and gene regulation.
Area of Science:
- Gerontology
- Molecular Biology
- Endocrinology
Background:
- Aging is associated with a decline in liver androgen responsiveness.
- This decline affects the synthesis of androgen-inducible proteins like alpha 2u globulin and the regulation of androgen-repressible proteins such as senescence marker protein (SMP-2).
Purpose of the Study:
- To investigate the effect of dietary restriction on age-dependent changes in androgen responsiveness in the rat liver.
- To determine if food restriction can mitigate the age-associated decline in androgen receptor sensitivity and specific gene expression.
Main Methods:
- Quantification of alpha 2u globulin and SMP-2 mRNA levels in liver tissues of young and aged rats under ad libitum feeding and dietary restriction.
- Measurement of cytoplasmic androgen-binding (CAB) protein levels.
- Correlation of gene expression changes with circulating testosterone levels.
Main Results:
- Food restriction significantly preserved alpha 2u globulin mRNA levels in aged rats compared to ad libitum-fed controls.
- Dietary restriction reduced the age-dependent increase in SMP-2 mRNA levels.
- While aging decreased circulating testosterone, dietary restriction did not alter this decline, suggesting a direct effect on liver androgen sensitivity rather than hormone levels.
Conclusions:
- Age-dependent changes in androgen-responsive gene expression reflect altered androgen sensitivity in the liver.
- Dietary restriction can maintain androgen receptivity in the aging rat liver, influencing the expression of key androgen-regulated genes.
- Food restriction may offer a therapeutic strategy to counteract age-related molecular changes in the liver.