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The effect of age on protein synthesis in mouse liver
Abstract:
1. A system of microsomes and 105000g supernatant from livers of old mice is less able to promote the incorporation of [(14)C]phenylalanine into protein than a similar system from livers of young animals. 2. The decrease in [(14)C]phenylalanine incorporation is attributable to changes in microsomes from old animals rather than in the cell-sap fraction. 3. Decreased synthetic ability is found in various classes of microsomes from older animals, namely unfractionated, light and heavy microsomes, but not in detergent-washed ribonucleoprotein particles. 4. Deletions of certain detergent-soluble microsomal proteins accompany the decreased synthetic ability of microsomes from older animals. 5. Microsomes from old mice are less responsive to a synthetic messenger RNA, polyuridylic acid, and this is partly due to a higher rate of hydrolysis in the presence of cell sap from animals of extreme age. 6. Other more direct evidence, from the priming of a cell-free protein-synthesizing system from bacteria and the examination of ribonucleoprotein particles on sucrose density gradients, suggests that senescence is accompanied by a decrease in messenger RNA content.
Insights
Protein synthesis declines in old mice due to changes in liver microsomes, not cell sap. This age-related decrease in protein synthesis is linked to reduced messenger RNA content and altered microsomal proteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Gerontology
Background:
- Cellular aging is associated with a decline in protein synthesis.
- The specific mechanisms underlying age-related decreases in protein synthesis in mammalian liver are not fully understood.
Purpose of the Study:
- To investigate the age-dependent changes in protein synthesis in mouse liver.
- To identify whether the decline in protein synthesis is localized to microsomes or the cell-sap fraction.
Main Methods:
- In vitro protein synthesis assays using liver microsomes and supernatant from young and old mice.
- Fractionation of microsomes and analysis of ribonucleoprotein particles.
- Assessment of messenger RNA (mRNA) content and activity.
Main Results:
- Liver systems from old mice showed reduced incorporation of [(14)C]phenylalanine into protein compared to young mice.
- The decreased synthetic ability was attributed to changes in microsomes, not the cell-sap fraction.
- Old mouse microsomes were less responsive to polyuridylic acid (a synthetic mRNA), and senescence correlated with decreased mRNA content.
Conclusions:
- Aging in mice leads to a decline in liver microsomal protein synthesis.
- This decline is associated with alterations in microsomal composition, including deletions of detergent-soluble proteins and reduced mRNA content.
- The findings suggest that decreased mRNA availability and/or function contributes to age-related protein synthesis impairment.