Another reason for aging: a mutation in the BAF-1 protein gene
A new cause of premature aging syndrome has been discoveredKirill Stasevich, Compulenta
A mutation in the gene of one of the proteins of the nuclear membrane causes progeria, or premature aging syndrome. However, according to scientists, mutations can cause not only acute genetic disease, but also normal aging.
A normal child and a child of the same age with progeria (photo by Ian Tomey).
Progeria, or premature aging syndrome, is a severe, albeit rare, genetic disease that cannot be treated. Wrinkled young men and old children are certainly a strong (and popular) artistic image, but molecular biologists are trying to solve the riddle of this disease not at all because of excessive impressionability. With the help of this genetic defect, scientists hope to uncover the general mechanisms of aging, and at the same time try to restrain it.
It is believed that the key to premature aging is in the cell nucleus – more precisely, in the membrane of the nucleus. The protein-lipid membrane does not just form a reservoir for storing cellular DNA: chromosomes are attached to it, and it performs a supporting and organizational function for them. In addition, the nuclear membrane controls the penetration of transcription factors into the nucleus – proteins responsible for activating or suppressing the work of certain genes. That is, violations in the structure and functioning of the nucleus will resonate throughout the genome.
Considering the whole complex of changes in the body that provokes premature aging syndrome, it becomes clear that in this case it is difficult to offer a more suitable cause than a malfunction in the nuclear membrane.
Previously, the main and only candidate for the causes of progeria was the protein lamin, one of the most numerous proteins of the nuclear membrane. Mutations in his gene were found in many patients with progeria. Many, but not all. A group of Spanish researchers from the University of Oviedo analyzed mutations in the genome of patients with "non-standard" premature aging syndrome (it should be clarified that scientists were engaged in the so-called pediatric progeria, or Hutchinson–Guilford syndrome). These people did not have problems with the cardiovascular system characteristic of ordinary progeria, they lived relatively longer, and they did not have a mutation in the lamin gene.
As a result, another "aging" mutation was found – in the gene of a protein called the factor that prevents autointegration-1 (BAF-1). The name is given for a reason: BAF-1 is able to prevent retroviruses from embedding their genome in the DNA of the host cell. Its "internal" function was unknown – until today. A mutation in the BAF-1 gene led to the development of multiple defects in the nuclear membrane due to the emerging instability of this protein. BAF-1 interacts with a number of other membrane proteins, so defects in its structure cause disturbances in the distribution of other membrane proteins. If the diseased cells are given normal BAF-1, then the symptoms accompanying the mutation disappear.
The results of the work are published in the American Journal of Human Genetics (Puente et al., Exome Sequencing and Functional Analysis Identifies BANF1 Mutation as the Cause of a Hereditary Progeroid Syndrome).
As the researchers themselves say, mutations in the BAF-1 protein can cause not only such severe and acute diseases as premature aging syndrome. A mutation leading to progeria dramatically disrupts the functioning of the protein, but during a person's life, many mutational changes in the BAF-1 gene can accumulate, which gradually weaken its structure, which leads to the same aging. Only delayed and stretched in time.
Prepared based on the materials of Medical Xpress: Mutation provides new insight into the molecular mechanisms of aging.
Portal "Eternal youth" http://vechnayamolodost.ru11.05.2011