Aging alters hepatic expression of insulin receptor and c-jun mRNA in the mouse.

The clear association between species and life span suggests that aging, like development, is genetically orchestrated. To explore this hypothesis, the expression of mRNA for a number of transcription regulatory and signal transduction proteins was investigated during aging of B10.RIII, C57BL/10 and B10.BR mice. mRNA for glucocorticoid receptor, CCAAT and enhancer binding protein, transcription factor Sp1 and RNA polymerase II elongation factor S-II were unchanged between 4 and 24 months of age in these mice. These factors are required for the normal transcription of many genes, perhaps explaining their steady rates of expression throughout life. Insulin-like growth factor I mRNA also remained unchanged. By contrast, mRNA for the insulin receptor and transcription factor c-jun changed significantly during aging. c-Jun mRNA decreased approximately 55% between 4 and 12 months of age and then increased by 24-25 months of age to levels approximately equal to those found in young mice. Insulin receptor mRNA increased approximately 30% by 24-25 months of age in all strains of mice. These results suggest that factors determining the steady state level of these mRNAs are altered in level or activity during aging. Assessing the causes and significance of these changes will require further study. However, our results demonstrate that alterations in the expression of specific regulatory genes occur during aging.