07 March 2013

How aging, autism and oxidative stress are related

Like any factory, the human body burns oxygen to produce the energy needed to meet its many needs. At the same time, toxic by-products are inevitably released, which the cells neutralize with the help of antioxidants. However, as the body ages, the protective antioxidant system gradually loses its position.

One of the solutions to this problem is to slow down the synthesis of new proteins, a process that requires high energy costs. Indeed, fewer proteins are produced in the aging body, which explains the deterioration in the ability to learn and repair damage observed in older people.

Since all proteins are synthesized according to instructions encoded in DNA, the process of their synthesis can be slowed down by suppressing the activity of certain genes. This is achieved through the operation of a mechanism known as epigenetic regulation, which consists in attaching and removing molecular labels to certain regions of the genome. The enzyme methionine synthase takes an active part in this process, the activity of which is regulated by the intensity of oxidation processes.

According to Richard Deth, professor at Northwestern University, this enzyme is the most oxidized molecule in the body. Under conditions of oxidative stress, methionine synthase ceases to function, which stimulates the synthesis of the antioxidant glutathione and has a pronounced effect on the metabolic activity of the body.

Des and his colleagues hypothesized that methionine synthase has an important regulatory role in the aging process and that its functioning may be disrupted in autism, the relationship between which and uncontrolled oxidative stress the authors identified in an earlier study.

To test this hypothesis, scientists studied postmortem samples of brain tissue of people of different ages (from 28 weeks of intrauterine development to 84 years). At the same time, they assessed the levels of informational RNA (mRNA) methionine synthase, which provides transcription of the genetic code of the enzyme under study into a protein product.

It turned out that as the human brain tissue ages, the content of mRNA methionine synthase decreases, but the concentration of the enzyme itself remains unchanged throughout life.

The authors suggested that the purpose of the observed age-related decrease in the level of mRNA methionine synthase may be to save energy and slow down the processes triggered by oxidative stress.

Comparison of the levels of mRNA methionine synthase and the enzyme itself in brain tissue samples of mentally healthy people and autistic people revealed significantly lower levels of mRNA methionine synthase in the brain tissue of the latter. At the same time, control samples and samples of patients with autism contained comparable amounts of the enzyme itself. Moreover, the tendency observed in the brain tissues of normal people to decrease the level of mRNA methionine synthase was not detected when analyzing brain tissue samples of people with autism.

If a decrease in the level of mRNA methionine synthase really means a decrease in the activity of protein synthesis, it does not matter much for the brain of adults who do not need to produce a large number of new protein molecules. However, the developing brain requires constant synthesis of new proteins. It turns out that cognitive abilities in children with autism may be prematurely reduced for metabolic reasons.

The results obtained are preliminary and need further confirmation, but they are additional proof of the validity of the hypothesis that has been developing recently, according to which both aging and autism are associated with oxidative stress.

Article by Christina R. Muratore et al. Age-Dependent Decrease and Alternative Splicing of Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism is published in the journal PLoS ONE.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Northeastern University:
A proposed link between aging, autism, and oxidation.


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