Abstract:
A new study by American researchers found that long-term reduction of food intake may not only affect lifespan and aging rate, but also change the way DNA mutations accumulate in body tissues. In one experiment with mice, mice that consumed 30% fewer calories per day accumulated fewer DNA mutations in multiple tissues than their counterparts that had free access to food. The discovery provides new clues to understanding how diet affects aging and disease risk.
This study was completed by researchers from NYU Langone Medical Center, University Hospitals of Cleveland, University of Texas Southwestern Medical Center, and the National Institutes of Health. The research paper was published in the journal Cell.
DNA is the molecule that stores genetic information, but it doesn't always stay the same. As we age, cells continue to experience DNA damage, replication errors, and deviations in the repair process, gradually accumulating somatic mutations. Most mutations will have no significant impact, but some mutations may interfere with the normal function of genes and increase the risk of cancer and other diseases. Therefore, figuring out which factors can slow down mutation accumulation is an important research direction in aging biology.
Scientists have previously found in a variety of animal experiments that caloric restriction may extend lifespan and slow down some age-related physiological changes. However, it has not been fully understood yet whether reducing caloric intake also affects genome-wide mutation accumulation.
To study this issue, the team used high-precision DNA sequencing technology to compare the genetic changes in the two groups of mice. One group of mice was allowed to eat freely, while the other group was subject to long-term caloric restriction, and their intake was about 30% less than that of the free-feeding group. The researchers then analyzed DNA mutations in different tissues to see whether dietary changes affected the accumulation of genetic damage.
The results showed that caloric restriction was associated with a reduction in a variety of DNA mutations, including base substitutions, and insertions and deletions of DNA segments. Base substitution means that one genetic letter in the DNA sequence is replaced by another letter; insertion and deletion mean that part of the genetic sequence is added or lost respectively.
However, this change is not equally evident in all organs. Liver cells responded relatively prominently to caloric restriction, while kidney and brain tissue showed varying degrees of change. This suggests that the effects of diet on DNA mutations may depend on the physiological characteristics of specific tissues, rather than reducing genetic damage to the same extent in all cells throughout the body.
The study also found unexpected differences in the effects of caloric restriction on different regions of the genome. In liver and kidney cells, the areas where mutations were most reduced tended to be parts of the gene with less activity. These regions may contain no genes or genes that are rarely used in the corresponding cells.
The researchers suggested that differences in DNA repair activity may be one reason. Gene regions in cells that are actively functioning are often subject to more frequent DNA repair, so the additional protection that caloric restriction can bring may be relatively limited. In contrast, areas with less normal repair activity may be more likely to show differences caused by dietary changes.
However, this is still an explanation that needs to be verified. The research team has not determined the specific mechanism by which caloric restriction reduces mutations, and cannot rule out the possibility that other cellular metabolic processes are involved. The researchers plan to further compare different diet regimens and analyze DNA mutations in more tissues and cell types to search for the underlying biological mechanisms.
Study co-author Gilad Evroni, associate professor at NYU Grossman School of Medicine, pointed out that the findings not only reveal a possible link between diet and lifespan, but also indicate that diet is related to the accumulation of mutations throughout the genome. He believes that understanding this connection is important because DNA mutations play a role in the development of cancer and many other diseases.
However, the researchers emphasized that this result cannot currently be directly translated into human dietary recommendations. The experimental subjects were mice, not humans; even if clear biological changes occur in animal experiments, it cannot be concluded that humans can achieve the same effect by reducing caloric intake by 30%.
In addition, long-term severe restriction of caloric intake is difficult to adhere to and may also lead to nutritional deficiencies, muscle loss and other health risks. Cutting calories doesn't mean you can skip protein, vitamins, minerals and other essential nutrients. In humans, further research remains to be done on exactly how much caloric reduction is needed, for how long, and whether this approach can actually reduce cancer rates or extend lifespan.
The research team hopes that the next step will be to find the key mechanism by which caloric restriction reduces DNA mutations, so as to develop intervention methods that do not rely on extreme dieting. If scientists can identify the molecular pathways that are truly protective, they may be able to reduce the accumulation of genetic damage during aging through drugs, nutritional strategies or other interventions in the future.
The significance of this study is not to prove that people should eat 30% less immediately, but to reveal the possible deep connection between diet and genome stability. It provides new directions for studying aging, cancer and other age-related diseases, but it is still a long way from clinically proven human health solutions.
Comments