Is Gaf1 the key to longevity?
Nowadays, people are living longer than ever before. But along with this increase in life expectancy, the number of age-related diseases, including cancer and dementia, is growing. Understanding the biology of aging, as well as knowledge of the function of genes and proteins involved in these processes, will help to increase the body's health reserve – a period when people can live in a healthy and productive state without age-related diseases.
An international group of scientists investigated the anti-aging properties of a relatively little-studied protein Gaf1 (Rodríguez-López et al., The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1 // Cell Reports, 2020). It controls protein metabolism, a process that plays a key role in aging and many diseases. Researchers have shown that without Gaf1, cells have a shorter lifespan.
Aging and diet
Aging is a complex process and depends on both genes and environmental factors, including nutrition. It is widely known that a calorie-restricted diet can increase life expectancy. This has been proven for a variety of organisms, including yeast, rats, and monkeys. Short-term studies show that judgment is also true for humans.
However, now scientists understand that in fact, the number of certain amino acids, and not the number of calories consumed, may be associated with life expectancy.
Each cell has a protein that is sensitive to the amount of nutrients in the environment. Such a protein is the target of rapamycin (TOR), an enzyme that determines the amount of amino acids present in the body and available to cells.
When there are a lot of amino acids in cells, TOR actively interferes with metabolism and forces them to grow, synthesizing a lot of proteins. But if the amount of amino acids is limited, TOR puts the body into a state of mild stress. It has been proven that it is useful for cells and the body as a whole, while increased translation (protein synthesis) and protein metabolism are harmful, because longevity is closely related to the body's ability to effectively cope with internal and external stresses. In other words, a cell that is "in a state of readiness" is able to cope with stress factors better than a cell that spends its energy on protein synthesis and growth, thus reducing protection.
In a recent study, scientists analyzed protein metabolism in the cells of different animals with a lifespan of four to 200 years. They found that in animals with longer lifespans, protein metabolism is much slower and energy requirements are lower.
Gaf1 and aging
The Gaf1 protein is a transcription factor, it is able to bind to the DNA of a cell and activate or suppress certain genes. When TOR is active, Gaf1 is detected in the cytoplasm of the cell and does not bind to DNA. However, when TOR is inactivated by food restriction or medication, Gaf1 can move into the nucleus and bind to DNA.
In an article in Cell Reports, the authors showed that when TOR binds to DNA, Gaf1 stops all the genes responsible for creating transport RNA and other genes necessary for translation. Gaf1 forces the cell not to waste energy on translation, preventing the creation of components necessary for this process. However, this is a temporary effect, it is reversible when amino acids become available.
The researchers also found that cells without Gaf1 are not durable. As already mentioned, TOR signals cells to grow, accelerating their aging. But when TOR is inhibited by food restriction or medication, growth stops, and cell lifespan increases. In other words, Gaf1 mediates some beneficial effects of food restriction.
Although the study was devoted to yeast (the TORC1 complex shown in the figure consists of TOR1 and three other proteins common to all eukaryotes), proteins similar to Gaf1 have been found in many animals, including humans. These proteins have been shown to regulate the process of stem cell development, the violation of which is important for the development of malignant neoplasms. Perhaps these proteins have the same function in humans as Gaf1 in yeast.
TOR function, cell growth and protein production are important for human health, but can also contribute to the development of certain diseases, such as cancer or Alzheimer's disease. This study has shown how dietary restriction alters intracellular metabolism at the gene level. This information will allow us to investigate how certain medications or diets can change the metabolism of cells for the health of the whole body.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to The Conversation: 'Anti-aging' protein shown to slow cell growth is key in longevity – new research.