Telomeres and aging: new data

Italians found abnormal structures in telomeres in elderly people

Polina Loseva, N+1

With age, people's telomeres not only shorten, but also acquire various anomalies, for example, split or merge with each other, – Italian scientists came to this conclusion after examining the blood of 35 volunteers. The number of telomeric anomalies not only increases with age, but also correlates better with it than the total length of telomeres, and therefore can serve as a more accurate marker of biological age. The work was published in the journal The Journals of Gerontology: Series A (Boccardi et al., Telomeres Increasingly Develop Aberrant Structures in Aging Humans).

The telomeric theory of aging suggests that human aging is caused by the inability of his cells to multiply. And it, in turn, is caused by shortening of telomeres – the end sections of DNA. The DNA copying system is designed so that with each division, telomeres become slightly shorter and, if they are not restored (which only stem cells can do), eventually reach a critical length, after which division is inhibited.

According to this theory, telomeres have long been considered one of the markers of biological age: the longer they are, the younger the body. No one doubts that short telomeres are an unfavorable sign: it correlates with the risk of development and death from various age–related diseases, including cardiovascular and oncological. But the telomere length itself does not correlate well with the chronological age of a person.

At the same time, there is another problem with telomeres. They are not just shortened during copying, but also form secondary structures (that is, they are twisted in the wrong way). In addition, they are more susceptible to oxidative stress than other DNA regions. All this leads to the fact that telomeres often break down, no matter how long they are, and this can also result in a stop of division.

Virginia Boccardi from The University of Perugia and her colleagues suggested that biological age may be more convenient to measure not by the absolute length of telomeres, but by the degree of their preservation. To test this assumption, they collected blood samples from 35 donors aged 23 to 101, isolated white blood cells from the blood and cultured them for two days.

The scientists then stained the dividing cells with a marker that selectively binds to telomeric DNA and counted the number of cells with telomeric abnormalities. These included the splitting of telomeres, the loss of a telomere on one of the copies of chromosomes (which were formed during division) and the fusion of telomeres from two copies of chromosomes. It turned out that the number of such structures significantly (p<0.001) increases with age. However, significant growth is observed only from 20 to 60 years: from 2.3 to 11.8 percent of chromosomes carry anomalies.

A – on the left: telomere staining in blood cells, on the right: types of abnormalities: cleavage (FT), loss (STL), fusion (STF). C – correlation of age and proportion of abnormal telomeres in cells.
A drawing from an article by Boccardi et al.

After that, the researchers calculated how the number of each of the anomalies individually changes with age. They found that the number of fragile (split) telomeres increases from 20 to 60 years, and then drops to 100 years. But the proportion of disappeared or merged telomeres grew continuously in all age categories. The authors of the work suggested that these anomalies were simply easier to notice on short telomeres than splitting.

Finally, the researchers measured the telomere length in 18 subjects. It, as expected, was not significantly correlated with age (p = 0.1252), but correlated with the number of telomeric anomalies (p = 0.0082).

Therefore, the authors of the work proposed to use in the future a more complex marker of biological age: the percentage of telomeric anomalies normalized by the total length of telomeres. This, on the one hand, will avoid distortions, which may be due to the fact that at different lengths, different numbers of anomalies can be recorded. On the other hand, a more complex marker will reflect all the problems associated with telomeres that arise in cells – they are prevented from multiplying not only by shortening the ends, but also by their deformation.

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