Telomeres and Huntington's disease
Progressive Huntington's disease shortened patients' telomeres
Polina Loseva, N+1
Scientists have found another disease under the influence of which telomeres become shorter – this is Huntington's chorea. At the same time, there are significant differences in the length of telomeres only when the disease has already manifested and progresses. This means that telomeres – and, apparently, the life expectancy of patients – are shortened not by the mere fact of the presence of a mutation, but by progressive disorders in the work of cells. The work was published in the journal Mechanisms of Aging and Development (PerezGrovas-Saltijeral et al., Telomere length analysis on leukocytes derived from patients with Huntington Disease).
Telomere length is often used as a marker of biological age and as a way to predict the likelihood of death for a patient. It is easier to measure than most other markers, but there are many difficulties with it. The spread on this indicator is quite large even at the birth of a child, and then during the life of the telomeres in individual cells can both shorten and lengthen. Therefore, scientists have repeatedly come to the conclusion that the marker should not be the length of telomeres in itself, but the speed of its change.
Despite this, works continue to appear, the authors of which measure the length of telomeres in people in different states. For example, a group of scientists led by Alberto Hidalgo-Bravo from the National Institute of Rehabilitation in Mexico City collected statistics on the length of telomeres in patients with Huntington's disease.
This disease is caused by an unusual mutation – the accumulation of repeats in the gene of the mitochondrial protein hantigtin. The more repetitions, the protein works worse, but it forms aggregates more easily and disrupts the mitochondria. The researchers selected 106 healthy people as controls (less than 36 repeats in the gene), as well as 100 people with a positive test result (more than 36 repeats), of whom 71 already had clinical manifestations of the disease, and 29 had not yet developed symptoms.
The authors found that in healthy people and in asymptomatic carriers of the mutation, the telomere length did not differ significantly (p=0.597), but in patients with progressive disease, telomeres were on average one and a half times shorter (p=0.011).
Tellingly, these differences had nothing to do with age. Despite the fact that patients with symptoms of the disease were on average slightly older than people from the other two groups, scientists did not find a clear dependence of telomere length on age within any of the groups. Therefore, they concluded that the shortening of telomeres is responsible for the changes that occur in cells during the development of the disease, and not the fact of the mutation itself.
Scientists suggest that the mechanism that binds the mutant protein to the telomere length is as follows. Huntingtin accumulates in the mitochondria and prevents them from working properly. As a result, more reactive oxygen species appear in them, and oxidative stress develops in the cell. Reactive oxygen species can escape from the mitochondria and damage telomeres (we recently talked about how they are particularly susceptible to stress). But a mutant protein has the ability to block repair proteins (we also wrote about how mutations in mitochondria prevent mutations in nuclear DNA from being repaired), so telomeres break down and become shorter.
There is still no effective treatment for Huntington's disease, but scientists are looking for ways to cope with it – for example, using autophagy or antisense chains of nucleotides.
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