Dietary calorie restriction could prolong female fertility and prevent genetic disorders that occur in eggs as they age, according to a mouse study published by the Proceedings of the National Academy of Sciences.
Thanks to this, it would be possible to preserve fertility longer without increasing the risk of birth defects in offspring, such as, for example, Down’s syndrome, which is the result of an additional copy of chromosome 21 appearing in the eggs as they age (chromosome is the structure in which DNA is packed in cells). – PAP).
We found that this way (i.e. by limiting calories – PAP) can – at least in mice – completely prevent virtually every aspect of the deterioration in egg quality typical of aging females, comments Dr Jonathan Tilly of Massachusetts General Hospital in Boston, who led the study.
His team also identified a gene that could be manipulated to improve egg quality in females on normal diets in a similar way to calorie restriction. This gives rise to hope that in the future it will be possible to prolong fertility with drugs that mimic the effect of a less nutritious diet.
So far, studies in various species of animals, including mammals, have shown that adults who are reduced in caloric intake – in such a way as to avoid malnutrition – live longer, age more slowly and have a lower risk of developing age-related diseases compared to with animals with unlimited access to food.
Human studies are currently underway to test the effects of long-term calorie restriction, but the results will not be known for some time. From observations conducted, among others however, on the group of Polish centenarians it appears that all of them went through longer or shorter periods of hunger in their lives.
Previous experiences of the team of Dr. Tilly has shown that female mice kept on a low-calorie diet for most of their adult life remain fertile at a very advanced age, even when allowed to eat freely at some point.
In this latest study, researchers tracked the fertility of two groups of mice from 3 months to 1 year of age, that is, from early adulthood to the age where the fertility and egg quality of these rodents typically decline significantly.
One group had free access to food during adulthood, while the other group was reared on a low-calorie diet for approximately seven months and had free access to food restored in the last month of the study.
As expected, the number of eggs released from the ovaries during ovulation decreased with age in mice at will, but fewer were mature and ready for fertilization.
In contrast, the cells of mice on a low calorie diet more closely resembled the healthy eggs of young females in their most fertile period of life.
Moreover, serious abnormalities in the number of chromosomes, such as an extra copy of one of the chromosomes, or the absence of one, were found in rodents’ eggs, which during adulthood had free access to food. There were no such age-related changes in the eggs of the females eating less.
Normally, in the production of reproductive cells – eggs and sperm – the number of chromosomes is reduced by half. The idea is for the egg and sperm to combine in the process of fertilization to give rise to a normal organism that has a double set of chromosomes – one from the mother and one from the father.
Cell division, during which the number of chromosomes in reproductive cells is reduced, is called meiosis.
Abnormalities during meiosis occur more frequently in the eggs of aging female mammals (including females). The result of this may be, for example, the complete absence of a copy of one chromosome, or an excess copy of another. As a consequence, there is a decline in fertility, an increased risk of miscarriage and of birth defects in offspring, such as the most famous Down syndrome, which is the result of an extra copy of chromosome 21 in a woman’s egg.
Dr. Tilly and his colleagues also observed that in the eggs of mice eating less, mitochondria, or structures that act as cell power plants, did not clump together and there was a decrease in energy production associated with it. This is typical of aging eggs.
Interestingly, it turned out that the eggs of freely eating mice can retain just as good quality as female eating less if they switch off the gene called PGC-1 alpha. It regulates the activity of genes in cells responsible for the control of the number and function of mitochondria, which means that it has a significant impact on cell metabolism.
The combination of a less caloric diet with inactivation of the PGC-1 alpha gene did not increase the effect of each of these methods used separately. This suggests that caloric restriction exerts its effects on fertility through the PGC-1 alpha gene.
While most of the research on the effects of calorie restriction has been carried out in mice and other laboratory animals, numerous studies in recent years have confirmed that the health benefits of it also apply to aging monkeys and possibly humans who chose to cut down on calories, comments Dr. Tilly.
In his opinion, if a way could be found to safely reproduce the effect observed in recent experiments in humans, it would be possible both to increase the chances of women getting pregnant later in life and to improve the quality of eggs in order to reduce, if not eliminate, the associated age disorders in the number of chromosomes. It is also important for those women who will still need to use assisted reproductive techniques, i.e. in vitro fertilization.
Joanna Morga (PAP)