Abstract

Healthy aging and human longevity are determined by a successful combination of genetic and non-genetic factors. Family studies have shown that about 25% of the variations in human life expectancy are due to genetic factors. The study of the genetic and molecular foundations of aging has led to the discovery of genes associated with cell maintenance and basic metabolism, which affect individual variations of the aging phenotype as the main genetic factors. Plus, studies of calorie restriction and gene variability associated with the transmission of signals about nutrients have shown that a low-calorie diet and / or a genetically efficient metabolism of nutrients can affect life expectancy, which leads to the effective maintenance of cells and the body. Recently, epigenetic studies have shown that epigenetic changes (patterns of epigenetic inheritance — changes in gene expression or cell phenotype caused by mechanisms that do not affect the DNA sequence), modulated by both the genetic structure and lifestyle, are very sensitive to the aging process and can either be a so-called biological marker of the quality of aging, or affect the speed and quality of aging.

Research

Biological aging is characterized by a progressive decrease in the ability to maintain homeostasis, which eventually leads to the development of age-related diseases and, finally, to death. However, we all age in different ways: some die before the age of 60 from chronic diseases, while others can live to a very old age and often do not have any serious health problems. Scientists from the University of Edinburgh and the Max Planck Institute for the Biology of Aging in Germany found out what this may depend on. Their study is published in the journal Nature Communications.

"The phenotypes of aging, such as healthy years of life, the total number of years lived and longevity, are of interest to all of us, but require exceptionally large sample sizes for genetic study. We took the existing summary statistics on the general genome <...> and identified 10 genomic loci that affect all three phenotypes, " the authors write.

They combined information from three publicly available datasets

• Zenodo,
• Edinburgh Databare
• Longevity Genomics

to perform the analysis in unprecedented detail. The array of information was equivalent to the study of 1.75 million lives or more than 60 thousand centenarians. According to biologists, most of these ten loci (the location of a certain gene on the genetic or cytological map of the chromosome) were associated with cardiovascular diseases, and some affect the expression of genes that are known to change their activity with age.

In particular, the genomic loci responsible for normal iron levels were represented in all three “aging phenotypes”. To confirm this, the scientists used a statistical method known as” Mendelian randomization " (uses genetic information to establish causal relationships between potential risk factors and the disease).

“We assume that the evidence for the participation of this factor in human aging is quite reliable. With age, heme synthesis (complex compounds of porphyrins with divalent iron, carrying one or two axial ligands. - Ed.) decreases, and its deficiency leads to the accumulation of iron, oxidative stress and mitochondrial dysfunction. In turn, iron accumulation helps pathogens maintain infection, which is consistent with a known increase in susceptibility to infection with age. In the brain, abnormal iron homeostasis is usually observed in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases and multiple sclerosis,” the scientists add.

Therefore, the genes involved in the metabolism of iron in the blood are partially responsible for a healthy and long life. The iron content in the blood depends on our diet, and abnormally high or low levels of it are associated with age-related ailments. In addition, among the signs of iron deficiency anemia (when the body cannot produce enough hemoglobin): weakness, rapid fatigue, shortness of breath, dizziness, brittle hair and nails, cold limbs, pallor.

"We are very excited about these data, as they strongly suggest that high levels of iron in the blood shorten our healthy life, and monitoring this indicator can prevent age-related disorders. We assume that our findings on iron metabolism will help explain why an excessive predominance of red meat too rich in iron in the diet is associated with age — related conditions, such as heart disease,” said Dr. Paul Timmers from the Usher Institute at the University of Edinburgh.

Conclusion

In addition, biologists are sure that the results of their research will open the way to the development of drugs to reduce the risk of developing age-related diseases, promote health and increase the chances of living to old age without diseases. The creation of a drug that could mimic the effect of genetic variability on iron metabolism may be a future step to overcome some of the consequences of aging. However, this will require further scientific research.