The website of Science Daily published an article on May 4, 2021, stating that according to a paper published in the journal eLife on the same day, researchers have found that people who live to be 105 years old or older often have a unique genetic background that makes their bodies more efficient in DNA repair. This is the first time that the genomes of “super – long – lived” people have been decoded in such detail, which helps us understand why they can live so long and avoid age – related diseases.
The first author of the paper, Paolo Garagnani, an associate professor in the Department of Experimental, Diagnostic and Specialty Medicine at the University of Bologna, Italy, said, “Aging is a common risk factor for many chronic diseases. We chose to study the genetic status of people over 105 years old and compared them with a group of relatively young and healthy adults from the same region in Italy.”
Garagnani’s team, in collaboration with several research institutions in Italy and the research team of Patrick Demombe of the Nestlé Research Center in Lausanne, Switzerland, recruited 81 semi – super – centenarians (over 105 years old) and super – centenarians (over 110 years old) from all over the Italian Peninsula. They compared these people with 36 healthy people with an average age of 68 from the same region.
They collected blood samples from all the participants and performed whole – genome sequencing to look for genetic differences between the older and younger groups. Then, they compared the latest research results with the genetic data in another previously published paper, which analyzed the data of 333 Italians over 100 years old and 358 people around 60 years old.
The researchers found that there were five common genetic changes in the group of people over 105/110 years old, involving two genes called COA1 and STK17A. Through comparison with the published data, they found that the same variants also existed in the group of people over 100 years old. Data prediction from computational analysis showed that this genetic variability could probably regulate the expression of three genes.
The most frequent genetic change was related to the increased activity of the STK17A gene in some tissues. This gene is involved in three aspects that are very important for cell health: coordinating the cell’s response to DNA damage, encouraging damaged cells to enter programmed cell death, and controlling the amount of dangerous reactive oxygen species in the cell. These are all important processes related to the occurrence and development of many diseases such as cancer.
The most frequent genetic change was also related to the decreased activity of the COA1 gene in some tissues. It is known that this gene is very important for the normal interaction between the nucleus and mitochondria. Mitochondria are the energy – producing factories in human cells, and their dysfunction is a key factor in aging.
In addition, the same region of the genome was also associated with the increased expression of BLVRA in some tissues. BLVRA can eliminate dangerous reactive oxygen species and is therefore very important for cell health.
The corresponding author of the study, Cristina Giuliani, a senior assistant professor in the Molecular Anthropology Laboratory of the Department of Biological, Geological and Environmental Sciences at the University of Bologna, said, “Previous studies have shown that DNA repair is one of the mechanisms that prolong the lifespan of various species. We have proved that this is also the case in humans. The data shows that the natural uniqueness of these long – lived elderly people in the last few decades of their lives is to a certain extent related to genes. This genetic change gives semi – super – centenarians the unique ability to efficiently manage cell damage throughout their lives.”
The team also measured the number of natural variations accumulated by people in each age group during their lifetimes. They detected seven genes and found that in the group of people over 105 and 110 years old, the burden of variation in six genes was much lighter. These people seemed to avoid the increase in age – related destructive mutations, which might have helped them resist diseases such as heart disease.
Another first author of the paper, Massimo Deledone, a full professor at the University of Verona, said, “This study is the first to conduct whole – genome sequencing on a wide – coverage group of super – long – lived people, which enables us to explore the genetic and natural genetic changes in the elderly.”
Another corresponding author, Claudio Franceschi, an emeritus professor of immunology at the University of Bologna, concluded, “Our research results show that the DNA repair mechanism and the low – variation burden of specific genes protect super – long – lived elderly people from age – related diseases.”
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