Most everyone knows about proteins, that product loved by bodybuilders and steak lovers alike. But how are they made? Ribosomes are the tiny factories responsible for churning out each and every protein that is used to build us up, carry out the reactions that keep us running, and enable us to move around. They take small amino acid building blocks and assemble these into chains of varying length that fold into their correct protein form. Ribosomes play a role in maintaining protein homeostasis in the body and therefore optimization of the ribosomal machinery is necessary to promote longevity. Previous studies have proven that, as with any other factory, over-working ribosomes and demanding large amounts of protein production decreases translational efficiency and accuracy. Therefore, obtaining the correct amount of functional ribosomal machinery is very important for proper protein production. A recent study conducted by Mathis, et al. investigated how the ribosome is turned over to maintain normal protein synthesis and whether diet affects ribosomal efficiency.  

       Ribosomes are micro-structures that are affected by our macro-diets; the body reacts to nutrient signals to regulate new ribosome assembly and ribosomal component exchange. Mathis, et al. sought to discover whether caloric intake affected ribosome efficiency, so they studied the effects of diet restriction in mouse livers. They extracted the ribosomes via a sucrose gradient (the ribosomes were centrifuged out based on their density in viscous fluid). The researchers found that the number of ribosomes remained constant between the two groups, yet the activity varied: the diet-restricted group’s ribosomal activity was significantly lower. This demonstrates that there were fewer lower number of ribosomes actively producing protein. The team then measured the incorporation of isotopes (atoms that differ only by their number of neutrons) into ribosomes. Isotopes allow you to mark newly synthesized structures with a signature or tag, allowing easy differentiation between old structures and new ones. From this experiment, the researchers were effectively looking the rate at which the ribosomes are changing and switching out their parts. Ribosomes are multi-unit assemblies composed of two substances: RNA (a structure that differs from DNA by one oxygen atom) and proteins. The team looked at the turnover rates of both of these materials in the ribosome. With both groups, as expected, the new rRNA was increasing over time with no significant change between the two groups.

       Their second measurement of ribosome activity came from studying the ribosomal protein turnover, consisting of synthesis and degradation rates. Although there was no significant differences in the data, they did observe slower median protein turnover with the diet-restricted mice. When they took a closer look, they found that many of the rates of protein turnover matched rates of RNA turnover in both experimental and control groups. According to this data, it suggested that entire subunits of the ribosome, including RNA plus protein, were being switched out. What was surprising was that the rate of ribophagy (ribosome degradation) was higher in diet-restricted mice. In fact, the ribosome turnover rate was 37 times greater relative to cell proliferation as compared to 25 times greater in the control. This means that with greater turnover, the ribosome’s most essential parts are being replaced more frequently, improving cellular fitness and whole organism lifespan. In essence, the shorter the lifespan of the ribosome and the less protein it’s responsible for cranking out, the more proficient and accurate the protein it creates will be. In addition, the researchers are finding that the parts of the ribosome that are being replaced with the greatest frequency and are the areas that are involved in the actual catalytic ability of creating the strings of amino acids, affirming the idea that greater turnover in these areas leads to more effective and higher quality production of proteins.

       As they delve further into the subject and continue linking causes for longevity with defined cellular process such as protein synthesis, they may help identify mechanisms of aging.


REFERENCES

Mathis, A. D., Naylor, B. C., Carson, R. H., Evans, E., Harwell, J., Knecht, J., … Price, J. C. (2017). Mechanisms of In Vivo Ribosome Maintenance Change in Response to Nutrient Signals. Molecular & Cellular Proteomics : MCP, 16(2), 243–254. http://doi.org/10.1074/mcp.M116.063255

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