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Lead Section

Telomere attrition is the shortening of the ends of chromosomes, called telomeres, which occurs naturally through aging. Many diseases have been seen to be influenced by this hallmark, such as pulmonary fibrosis.

Hallmark Summary

At the end of replication, DNA polymerase is not able to replicate the ends of linear chromosomes, telomeres, where the RNA primer once was. This inability, leads to telomere shortening and the lose of genetic information, unless the cell is one of few which has the enzyme telomerase, which accounts for the loss from DNA polymerase. For cells without telomerase, DNA polymerase’s incapability to replicate the telomeres leads to a shortening of the chromosome over time. A lack of telomerase can also lead to many diseases, all having to do with a loss of regenerative capabilities. Due to this observation, telomere attrition has been strongly linked to aging, as described in “The Hallmarks of Aging” review article. It has also been seen that telomeres endure much more age-related DNA damage than other parts of the chromosome, which further contributes to telomere attrition, strengthening its role in aging.

Besides telomerase, another protective measure that telomeres possess is the shelterin complex, which binds to the telomeres, preventing neighboring chromosomes from being joined due to DNA damage repair mechanisms. This complex is of importance because a malfunction of this complex can lead to accelerated aging.

Studies have shown that the length of telomeres correlates with the lifespan of an organism. Mouse models with shortened telomeres had a shorter lifespan and mice with longer telomeres had a longer lifespan. Also, using mouse models, it was seen that if telomerase was active, this would lengthen the life of the mice for a certain period, therefore making a positive connection between telomerase levels and overall lifespan. With this experimental knowledge, telomere attrition is considered a hallmark of aging.

Progress since 2013

There has been a significant amount of research regarding telomeres and aging since the "Hallmarks of Aging" review paper. Many researchers have focused on determining whether other organisms, such as birds, rodents and fish have shortened telomeres as they age. One example is the zebrafish, which was found to have shorter telomeres in key tissues which lead to aging, both within the tissue but also the organism as a whole. Another example was performed in plants, Arabidopsis, and the authors found that telomere dynamics were connected to meristem activity and continuous growth of the plants. Contrasting from humans, plants and zebrafish, the edible dormouse had elongated telomeres as they aged, which was accredited to a reproduction strategy which makes them not reproduce during times of low food. The mechanism by which the edible dormouse elongates its telomeres has not been excessively looked at since the present paper is recent.

It was also found that environmental factors can play a role in the shortening of telomeres. A study was done with arctic breeding kittiwakes studying the effect of oxychlordane on telomere length. Oxychlordane belongs to a type of chemicals which are persistent organic pollutants (POPs). Arctic breeding kittiwakes were used because the arctic is where POPs get absorbed into the marine life and get eaten by the seabirds.The authors discovered that oxylchlordane was strongly associated with shorter telomeres in this particular bird, but only in females. This sex-selectivity could possibly be due to the increase in susceptibility to oxychlordance by egg production.

Telomere dysfunction/deficiency has been linked to a number of diseases including pulmonary fibrosis. A recent article showed the mechanism by which telomeres affect and lead to the onset of pulmonary fibrosis via the Trf1 gene in mice.