Scientists recently discovered a number of "super-mutations" that exist in human cells from birth that could potentially years of a person''s life. Genes and the environment Scientists estimate that each of these DNA variants are most likely inherited from parents and can reduce life span by up to six months. The various combinations of these can also determine people''s longevity even before they develop age-related diseases such as cancer, diabetes and dementia.
A person''s genes alone do not determine a certain normal age, as diet and many other factors play large roles as well. Studies show that variants of DNA methylation can influence the aging process. Biologists place less than a third of this effect on genes that humans inherit. The source of other differences in DNA that affects lifespan is the environment, such as sun damage, exposure to chemicals, and other forms of harm that thousands of random mutations. Each cell group differs from these environmental mutations, and most do not significantly affect a person''s lifespan.
Rare mutations
Searching for rare mutations, which are found in less than one in 10,000 people, requires a significant team effort. Harvard geneticist Vadim Gladyshev, one of the senior co-authors of the new study published on eLife in April 2020, has partnered with his academic colleagues and the Russian biotechnology company in Moscow, Gero LLC, to research the ''British Biobank'', which is considered a base. Public data containing the genotypes of approximately 500,000 people, which facilitated investigation of the relationship between genetics and longevity.
Although it is not yet possible to directly study longevity with data in the UK Biobank, several genome-wide association studies have used this data to study native life-span characteristics such as parental age and individual health.
Life span is defined as the number of years an individual lived in the absence of major chronic diseases. These studies have been reasonably successful in identifying new genetic variants that affect human lifespan, but they can only explain 5 percent of the inheritance of age-related traits.
Likewise, Gurs Dillen, a researcher from the Max Planck Institute for Aging Biology in Germany, says in a study of more than 40,000 individuals and published on eLife in April 2020 that carrying a small number of extremely rare genetic variants is associated with a longer lifespan.
It is possible that rare variants are able to explain what is sometimes called "missing heritability."
Gene blocking
A type of rare gene variant called the "protein truncation variant PTVs" can greatly affect gene expression (that is, the activity of genes in protein production) by disrupting the reading of the protein''s gene sequence. Gladyshev''s team counted the number of these rare protein truncation variants that were present in each individual''s genome, and found that they were negatively associated with health and age. This indicates that individuals with a small number of them are more likely to have a longer, healthier life.
As for harmful mutations and their role in aging, the researchers noted that on average, each person is born with six different options that can reduce the life span and life span, and as the team reported, the greater the number of mutations, the greater the person''s likelihood of developing an age-related disease at a younger age or dying early.
It appeared that the rare, harmful inherited mutations accumulating throughout life contribute to the aging process. Gladyshev adds that although the exact composition is important, but in general, each mutation reduces six months of the life span and two months of the recovery period from diseases.
Scientific controversy
The results are based on what is already known about aging known as "family genes." But instead of studying common mutations found in long-lived people, researchers can now target rare variants found in everyone. Gladyshev hopes that this information will be used in clinical trials to classify participants according to their mutations, as well as things like gender and actual age.
These results may be controversial because they reduce the perceptible contribution to aging due to "physical" environmental mutations acquired throughout life. In addition, changes in hormones and changes in gene expression also come with age. And they all contribute to the aging process and not because of any of them alone.
Jan Vij, a geneticist at Albert Einstein College of Medicine in the United States who studies the role of physical mutations in aging, agrees with Gladyshev despite saying that physical mutations can cause diseases like skin cancer. It reduces the life span. He adds that there may be a limit to the life span of humans, based on what was previously published in the magazine "Nature", where the maximum longevity was set at 115 years. But Alexis Patel, a biomedical engineer at the Johns Hopkins University School of Medicine in the United States, has important reservations about Jan Feige’s statement that the new research only looks at the “exome,” which is 1 percent of the genome that actively builds proteins. Which directs cells, the rest is largely unknown although mounting evidence shows that it can influence gene expression.
Finally, from the foregoing, we conclude that the genetic variants identified so far can explain only a small part of inheritance in humans, and that rare harmful mutations inherited and accumulated throughout life contribute to the aging process.
