Gene aging
Scientists have long been interested in the question of whether somatic (not inherited) mutations play a role in brain aging and the development of neurodegenerative diseases, but technology did not allow them to answer it. To do this, it was necessary to order the genome of a single cell, because each mutation is unique.
Researchers from Boston Children's Hospital and Harvard Medical School, using the method of genome-wide sequencing of individual neurons, analyzed cells one by one and searched for evidence in favor of the accumulation of acquired mutations by brain cells.
One of the findings of the study: mutations accumulate faster in individuals with genetically determined abnormalities that lead to early aging.
The group performed a genetic analysis of 161 nerve cells. The material was taken from postmortem samples of the Neurobiobank of the National Institutes of Health (National Institutes of Health). The samples belonged to 15 neurologically healthy people aged 4 months to 82 years and 9 people with one of two genetic disorders leading to premature aging or neurodegeneration – Coccain syndrome or xeroderma pigmentosa.
The latest methods of data collection and analysis have made it possible to detect mutations of one nucleotide in the genetic code of each neuron. The cells under study had to strengthen their genome by generating multiple copies before analysis. The new methods made it possible to exclude experimental artifacts, taking into account only true mutations.
The studied neurons were taken from two brain regions: the prefrontal cortex and the hippocampus. Neurodegenerative and age-related changes are most evident in both of these areas.
In the neurons of neurologically healthy people, mutations accumulated with age in both parts of the brain. Faster accumulation occurred in hippocampal neurons. The reason for this, according to researchers, is the high ability of hippocampal cells to divide.
In the neurons of the prefrontal cortex of people with Coccain syndrome and pigmented xeroderma, an increase in the number of mutations was observed with age – twice as fast as in the neurons of the same part of the brain of neurologically healthy people.
Researchers have proposed the term "genosenium" (genosenium, from the combination of the words genome and senescence). Gene aging is an irreversible process of gradual accumulation of mutations in neurons that lead to aging of the brain.
The accumulated mutations were analyzed, which allowed them to be divided into three groups.
The first group of mutations accumulated with age regardless of the state of the nervous system. The accumulation of mutations of the second group did not correlate in any way with age or concomitant diseases. The third group of mutations was associated with the processes of DNA oxidation and damage, their number increased with age and strongly correlated with neurological diseases. Thus, in the neurons of neurologically healthy people, they accumulated more slowly than in the presence of Coccain syndrome or pigmented xeroderma.
The results of the study provide a lot of food for thought. One of the questions that arise after reading the conclusions: are neurodegenerative diseases so much different from oncological ones? After all, both processes are based on DNA mutations accumulating in cells.
In addition, the study points to the role of oxidation processes and the possible benefits of antioxidants in the fight against neurodegenerative and age-related changes.
Currently, researchers are focusing on studying the effect of mutations on the DNA of neurons in other neurodegenerative diseases.
Article by Michael A. Lodato et al. Aging and neurodegeneration are associated with increased mutations in single human neurons published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru .