Another aging mechanism: nuclear pores
Old age from cosmetic repairsPeter Smirnov, "Газета.Ru ".
Perhaps the main cause of cell aging has been found. The pores of the nuclear membrane were unlucky – they only need cosmetic repairs during the life of the cell. The wear of the inner, working part of the pore is not compensated, and over time it begins to "flow", passing molecules inside the nucleus that should have been kept outside – and vice versa.
The last two or three years have literally been a breakthrough for gerontology. First, scientists found a way to prolong the life of yeast, worms and even mice by fasting, then several genes that can prolong active longevity. It was even possible to find a connection between the development of the reproductive system, adipose tissue and life expectancy.
But the approach to the molecular and cellular foundations of aging has not changed for several decades: the accumulation of mutations that inevitably occur during division, the gradual destruction of proteins and the depletion of "reserve" systems.
Martin Hetzer from the Salk Institute for Biological Research and his colleagues were able to significantly clarify this understanding: behind the general words about wear, there is at least a malfunction of the nuclear pores that ensure the selective exchange of contents between the nucleus and the cell.
The figure shows a view of the nuclear pore (from the cytoplasm side) under an electron microscope and a diagram of its structure
Despite the microscopic size – from five to a hundred micrometers, the cell itself includes several dozen more organelles, the main one among which is the nucleus, which provides regulation of all intracellular and even extracellular processes. Inside the nucleus, which can occupy up to 80% of the volume (in spermatozoa), the most valuable thing is located – genetic information encrypted in the DNA sequence.
If it were not for the nuclear envelope, the number of mutations and failures in reading the code would simply not allow the cell to live. But despite the double membrane surrounding the chromosomes, the genetic apparatus is not isolated: different types of RNA constantly leave the nucleus, regulating protein synthesis, while signals that activate transcription factors penetrate inside.
As in the case of more "large" barriers operating at the level of the whole organism, the nuclear one also has selective permeability: for example, fat-soluble molecules, whether steroid hormones or certain medicinal substances, easily penetrate through the membrane itself, more like a thin oil film with inclusions.
But nucleic acids, proteins and other hydrophilic compounds are doomed to pass through special channels – nuclear pores. Despite the variety of molecules passed through, the pores themselves are quite conservatively arranged in most organisms and consist of an internal channel and symmetrical outer parts, similar to protein molecules located at the vertices of an octagon.
As shown by Hetzer and co-authors of a publication in the journal Cell (M. D'Angelo et al., Age-Dependent Determination of Nuclear Pore Complexes Causes a Loss of Nuclear Integrity in Postmitotic Cells), over time these pores begin to "flow", which causes more "noticeable" consequences – the deposition of amyloid plaques along the vessels brain, destruction of cartilage in the joints, "senility" of the heart.
Using the example of muscle cells, and then the whole organism of the nematode C. elegans, scientists have demonstrated that the peripheral part of the nuclear channel is regularly updated, while the central one is rebuilt only during cell division, in which the shell of the nucleus is first destroyed and then formed again. Accordingly, the nuclear pores gradually "wear out", but, unlike other intracellular systems, they are not updated, which leads to a "leak". As a result, not only mutagens enter the nucleus, but also other molecules that disrupt the work of the genetic apparatus.
If it concerns constantly renewing skin cells or intestinal epithelium, then such a problem does not arise, but what about nerve or muscle cells that practically do not divide throughout life? It is not surprising that their metabolism is tied not only to "signals" from the nucleus, but also to well-established cascades of reactions that do not require rapid intervention of the genetic apparatus.
Hetzer's discovery did not become another "self-sufficient" hypothesis in the theory of aging. Scientists have demonstrated how reactive oxygen species, which have long been the main enemy of gerontologists, are able to accelerate the wear of nuclear pores, and with it the aging of the entire cell. It remains to be hoped that a system compensating for these "leaks" still exists, and if it can be detected, it will become a new round in the study of active longevity.
Portal "Eternal youth" www.vechnayamolodost.ru28.01.2009