Are "runaway" proteins another cause of aging?

Researchers from the University of Florida, together with their colleagues from other scientific centers in the United States, have identified a protein that plays a key role in the processes of oxidative damage to cells, ultimately leading to age-related hearing loss. The results obtained (they will be published this week in the Proceedings of the National Academy of Sciences) will help develop new strategies for antioxidant therapy of senile hearing loss, and in the future – other age-related diseases.

Age-related hearing loss is one of the most common sensory disorders in the elderly. Scientists are still trying to figure out which cellular processes determine hearing loss or contribute to its loss. Due to the high prevalence of this disorder, age-related hearing loss is currently a serious social problem.

One of the theories of aging claims that free radicals damage the components of mitochondria. These damages accumulate and over time lead to leakage of certain proteins from the mitochondria. Inside the mitochondria, these proteins are vital, but when they leave them, they become deadly. Cell death caused by such "runaway" proteins manifests itself in the form of physical effects associated with the aging process, including hearing loss.

Age-related hearing loss implies the death of sensitive hairs, nerves and membrane cells in the inner ear. Since the hairs and nerve cells in humans do not recover, their death leads to a gradual loss of hearing.

It is known that one of the proteins called Bak weakens the mitochondrial membrane. The higher the concentration of this protein, the weaker and more permeable the mitochondrial membranes become, allowing harmful molecules to enter the cell.

Bak is usually formed as a result of oxidative stress, and its level increases as the body ages. Researchers were interested in the question whether the absence of this protein can prevent age-related hearing loss associated with the death of sensitive hairs, nerves and membrane cells in the inner ear.

Tests for hearing acuity showed that middle-aged mice with a lack of Bak protein had the same hearing indicators as young mice. In addition, a smaller number of important auditory cells turned out to be dead compared to "wild" mice that do not suffer from Bak deficiency.

The researchers also decided to study how resistant the inner ear cells of Bak-deficient mice are, for which they exposed them to a special reagent that causes oxidative stress. It is oxidative stress that induces Bak expression in inner ear cells.

During the experiment, only a slight loss of snail cells was observed at all doses of chemical stress tested, in contrast to the level observed in wild-type animals. Thus, the scientists concluded that the Bak protein contributes to the death of cochlear cells as a result of oxidative stress.

It is logical to assume that if oxidative stress causes the destruction and death of hearing aid cells, strengthening the antioxidant protection of mitochondria should help reduce the level of damage.

The researchers found a delay in age-related hearing loss in animals with an excessive amount of an enzyme that neutralizes reactive oxygen species, as well as in animals receiving oral antioxidant preparations.

These observations seem to point to an effective biological target that can be used for targeted therapeutic effects. The main question remains the timing – when to start using antioxidants, in what combinations and doses.

Another way to reduce oxidative stress – calorie restriction – is also to some extent able to prolong life and prevent age-related hearing loss, which was previously demonstrated in one of the experiments on mice. Based on the new data, the researchers believe that the likely mechanism by which calorie restriction works is a decrease in cellular mortality induced by the Bak protein.

Professor Huber Warner from the University of Minnesota gives a promising assessment of the work: "The results of this study highlight the idea of extending life by limiting calories into a completely new industry that has not been studied before." The scientists' conclusions show that instead of calorie restriction affecting the metabolism as a whole, local regulation of the Bak protein level is possible to affect specific human biological systems, whose functions are primarily disrupted during aging.

Ruslan Kushnir
Eternal Youth Portal www.vechnayamolodost.ru according to Eurekalert: 'Escaped' proteins add to hearing loss in elderly, UF researchers find13.11.2009