In a recent study, the novel anti-aging protein Gaf1 was identified, it was found to control protein metabolism which has been implicated in aging and disease; cells without Gaf1 were found to have a shorter lifespan.
The complex process of aging depends on genetic and environmental factors such as diet. Calorie restricted diets have been shown to promote prolonged lifespans, and this holds true for a variety of organisms with short term studies suggesting that it also helps to improve human health.
Emerging evidence now suggests that it may actually be the quantity of specific nutrients such as amino acids that are linked to the increased longevity rather than the amount of calories consumed. Cells can sense the amount of nutrients in their environment through specific molecules within the cells such as TOR which senses the amount of amino acids that are present in the body and available to the cells.
Amino acids are the building blocks of proteins, when our body has an ample supply the TOR enzyme will trigger our metabolism to instruct the cells to grow by making a lot of proteins, this process is called protein translation. However, if amino acids are low TOR will instruct the body to be on alert which is referred to as a mild stress response that is thought to be beneficial for the cells and the organism overall while increased protein translation and turnover is detrimental.
Longevity is related to an organism’s ability to find a way to effectively manage both internal and external stressors. Cells that are on alert have been shown to cope better, as when a cell invests in protein translation and growth it lowers its defenses and is not able to cope with stress as effectively.
A recent study analyzing the turnover of proteins within cells of different animals with lifespans ranging from 4-200 years found that the longer lived animals had lower protein turnover and energy demand within their cells as compared to the shorter lived animals.
DNA carries genetic information, genes are pieces of DNA and many are responsible for making proteins. For a protein to be made the cell needs to produce a mRNA copy of the corresponding gene through a transcription process; mRNA guides the cell ribosomes on the order that amino acids should be linked together to make proteins.
Cells also require ATP energy, amino acids, and small tRNA molecules for protein translation which takes a lot of energy; each cell may need tens of thousands of ribosomes to translate its proteins. The more food a cell has the more active TOR will be instructing the cell to grow and divide. When TOR is inactive as in dietary restriction it will stop translation by preventing existing ribosomes from functioning, as well as stopping the production of new ribosomes.
Scientists recently discovered new function of the Gaf1 protein which is a transcription factor that is able to bind on cell DNA and activate/repress specific genes. When TOR is active Gaf1 can be found in the cytoplasm of the cell and it does not bind on the DNA, but when TOR is inactivated Gaf1 can travel to the nucleus and bind to DNA. When it binds to DNA it stops all the genes that are responsible for making tRNAs as well as other genes needed for translation. This is done by controlling a network of genes that are responsible for providing all of the building blocks for making proteins to stop the cell from putting energy into translation by preventing it from making the components needed for the process; but this is only temporary as when amino acids are available this halt is reversed.
Cells lacking in Gaf1 have been found to be short-lived; TOR signals cells to grow which contributes to aging, but when TOR is inhibited the growth is halted and extends lifespan. When Gaf1 is not present growth is not halted and the observed extension in lifespan is not taking place fully, meaning a molecule was found by the scientists that mediates some of the beneficial effects of dietary restriction.
This study was examining yeasts, but proteins similar to Gaf1 exist in many animals which includes humans, and they have been shown to control development as well as stem cells which are important in whether we develop diseases. It may be possible that these proteins have the same functions in humans that were observed with Gaf1 in yeast.
TOR function, cell growth and protein production are important to physiology and healthspan but they can also contribute to the development of certain diseases. This study has demonstrated how dietary restriction is controlled down to the cell’s genes, and the findings may allow for the examination of how specific drugs or diets can work to enhance the function of these factors for beneficial effects that may even increase human healthspan.
