Abstract
The effect of aging on the expression of alpha 2u-globulin was studied in liver tissue from 6-30-month-old male Fischer F344 rats. The synthesis of alpha 2u-globulin by suspensions of isolated hepatocytes decreased 90% between 6 and 22 months of age. The levels of alpha 2u-globulin mRNA and the transcription of alpha 2u-globulin genes by isolated liver nuclei decreased 80-85% between 5 and 24 months of age. Because alpha 2u-globulin has been suggested to be a "senescence marker protein," the expression of alpha 2u-globulin was measured in rats fed a diet restricted in calories. This dietary restriction procedure has been shown to increase significantly the longevity of rodents. The expression of alpha 2u-globulin was compared in liver tissue from 18-month-old rats fed ad libitum and a restricted diet (40% restriction of total calories). The synthesis, mRNA levels, and transcription of alpha 2u-globulin were 1.8-3-fold higher for liver tissue from restricted rats compared to liver tissue from rats fed ad libitum. Therefore, dietary restriction alters the age-related change in the expression of alpha 2u-globulin. Our results demonstrate that the changes in alpha 2u-globulin expression that arise during aging or dietary restriction are regulated at the level of transcription.
Highlights
The effect of aging on the expression of az.-globulin was studied in liver tissue from 6-30-month-old male
Our results demonstrate that the changes in az.-globulin expression that arise during aging or dietary restriction are regulated at the level of transcription
Preliminary studies by Roy’s laboratory (14, 18) suggest that the decrease in az,globulin synthesis with age is due to changesin mRNA levels, which indicates that agingis acting ata pretranslation site in the regulation of a,-globulin expression
Summary
Animals-Male Fischer F344 rats were used in thisstudy. The rats used to study the effect of aging on the expression of a2u-globulin were obtained from the animal colony maintained by the National Instituteon Aging. Identical results were obtained with poly(A)+ in two groups of 18-month-old ratswas measured: rats fed ad RNA isolated from the livers of 5-29-month-old rats (data libitum and rats thatwere placed on a restricted diet (60% of notshown).,the decline in a,,-globulin mRNA ad libitum) a t 6 weeks of age. The sions of hepatocytes, the synthesisof as,-globulin by hepatolevel of as,-globulin mRNA in hepatic RNA decreased over cytes isolated from rats fed ad libitum and the restricted diet 85% between 6 and 24 months of age. The incorporaobserved with RNA isolated fromyoung and old male C57B1/ tion of ['Hlvaline into as,-globulin was significantly greater 6J mice (data not shown).T o determine whether the change for hepatocytes isolated from the restricted rats.
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