02 October 2014

Does brain aging begin in the vascular plexuses?

How to Stop Brain Aging

Alexandra Bruter, <url>The authors of a paper published recently in the journal Science (Baruch et al., Aging-induced type I interferon response at the choroid plexus negatively affects brain function) have found out what brain aging is expressed in.

They even suggested a way to scroll back in time.

The achievements of modern medicine in the fight against somatic diseases have raised the average life expectancy to a previously unattainable height. Now we are increasingly talking about the need to fight not only for the duration of life, but also for its quality. And the quality of the last decades of life strongly depends on the degree of cognitive decline. It is important to solve this problem not only from an economic point of view – so that most people are able to work, but also from a humanistic point of view – by thinking better and remembering more, you can lead a much more interesting and eventful life.

How is brain aging related to body aging? The answer to this question is not so obvious. It is believed that aging of the whole organism as a whole has two main mechanisms: one is associated with the activity of the peripheral immune system, and the other with substances circulating in the blood. The brain is separated from the rest of the body by a hemato-encephalic barrier, which should prevent any metabolites or chemical signals from other organs from entering the brain (we wrote a little about this yesterday). Brain cells divide far from everything and very slowly, so replicative aging associated with telomere shortening is also not their case. However, cognitive abilities deteriorate with age, and it's not just neurodegenerative diseases like Parkinson's disease and Alzheimer's disease.

In the vertebrate brain, in almost every ventricle of the brain, there are formations called vascular plexuses. These are villous structures consisting of epithelial cells, they produce cerebrospinal fluid. Cerebrospinal fluid surrounds the brain. Vascular plexuses are the places "closest" to the brain where information from the rest of the body gets to.

The authors considered it likely that the processes associated with brain aging occur precisely in the vascular plexus. To find out what these processes are, the authors analyzed the activity of a large number of genes in the vascular plexuses of mice aged 3 and 22 months (in total, laboratory mice live about two years).

The most accurate ways to analyze the activity of genes are to analyze the number and activity of different proteins. But this is a very time-consuming and expensive procedure, so when it is necessary to analyze a lot of genes, it is not used. In this case, the matrix RNA (mRNA) is analyzed. Recall that mRNA molecules are synthesized in the nucleus on the basis of genomic DNA, they are sent to the cytoplasm, and there ribosomes synthesize proteins based on them. It is quite easy to isolate RNA from cells. Then, in test tubes, with the help of viral reverse transcriptase proteins (they turn the genome of RNA-containing viruses consisting of an RNA molecule into DNA so that it can be embedded in the host genome), DNA molecules corresponding to mRNA are synthesized. The next step is sequencing. All the resulting DNA molecules are read, and count how many molecules corresponding to individual genes. The more DNA, the higher the activity of genes.

It turned out that during the aging process, the expression of genes in the vascular plexuses is activated, which are usually associated with the activation of type I interferons characteristic of viral infection. Tests of mice kept in a variety of conditions in different scientific centers around the world have confirmed that this find is hardly an artifact caused, for example, by a real viral infection among mice in the same laboratory. Moreover, similar phenomena were found earlier in the brain of older people. On the contrary, the activity of genes associated with type II interferons was reduced.


Immunofluorescence image of the vascular plexus.
Epithelial cells are colored green, the chemokine protein (CXCL10) is red.
Figure from the Weizmann Institute press release Scientists Identify the Signature of Aging in the Brain - VM

To check whether these changes are caused by substances from the bloodstream, scientists conducted a rather complex experiment to combine the blood flows of two mice: an old and a young one. Such a combination is performed surgically, the method is usually used just to find out whether any substances circulating in the blood play a role in the phenomenon under study. The experiment yielded only partially positive results: there were partially corresponding changes in the activity of group II interferon genes, but nothing happened to the activity of group I interferon genes. This means that in the first case, both factors produced by the body and factors produced by the brain are involved in regulation. But the group of type I interferons is affected only by the brain itself.

There is also good news. It consists in the fact that if elderly mice with memory impairment block signal transmission in the brain by interferons of the first group, then the memory impairment recedes, and the formation of new cells in the brain intensifies. Perhaps this observation will help in the future to combat age-related memory disorders in humans as well.

Portal "Eternal youth" http://vechnayamolodost.ru02.10.2014

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