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Telomerase

Many organisms have a ribonucleoprotein enzyme called telomerase, which carries out the task of adding repetitive nucleotide sequences to the ends of the DNA. Telomerase "replenishes" the telomere "cap" and requires no ATP to complete its function.  In most multicellular eukaryotic organisms, telomerase is active only in germ cells, some types of stem cells such as embryonic stem cells, and certain white blood cells. Telomerase can be reactivated and telomeres reset back to an embryonic state by somatic cell nuclear transfer. The steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence and in the prevention of cancer. This is because the telomeres act as a sort of time-delay "fuse", eventually running out after a certain number of cell divisions and resulting in the eventual loss of vital genetic information from the cell's chromosome with future divisions.

Association with Aging

Telomere shortening is associated with aging, mortality, and aging-related diseases. Based upon comparison between individuals of different ages, telomere length is negatively associated with the number of cell divisions in germ and tumor cells. This leads to the link between age and telomere length, as one might expect, the older an individual is the more times their cells have replicated their genome and divided. Normal aging is associated with telomere shortening in both humans and mice, and studies on genetically modified animal models suggest causal links between telomere erosion and aging. In contrast to humans, mice have been demonstrated to have significantly longer telomeres. This could demonstrate how the effects of telomere shortening might have a different or no effect on other eukaryotes, as the older mice had no significant difference in telomere length than younger mice. Furthermore, the role and importance of telomeres appears to have varying degrees of importance among model organisms. Common model organisms such as mice, S. cerevisiae, and C. elegans, were able to withstand the knockdown of telomerase with little effect for multiple generations. Despite the resiliency of these eukaryotes, a decrease in telomerase function in humans resulted in multiple threatening complications after only a few generations. This carries implications on the importance of preserving telomeres in human health.

The age of a father plays a role in the length of a child's telomeres, which has evolutionary implications. Although leukocyte telomeres shorten with age, sperm telomeres lengthen with age. Shorter telomeres are theorized to impose lower energy costs (due to less replication) but also have immune system-related and other aging- and disease-related costs, so the effect of paternal age on telomere length might be an adaptation to increase the chances that the child will be fit for the environment they're born into. Telomerase is normally triggered by cancer cells, however in some cases, cancer cells use a mechanism called alternative telomere lengthening to retain telomeres.[citation needed]

A recent study in Israel sought to find the association between telomeres, and whether it is a causation or correlation with the aging of humans. Researchers designed an experiment using 35 patients all of which were over 64 years of age and all of whom had no extensive distinguishing medical problems/complications. Each person was subject to 60 oxygen therapy sessions per day during the course of the experiment. During each session, the people would be placed in a hyperbaric chamber in which they were fully enclosed. Their results found that the telomeres in the participants were significantly longer, about 20% longer when compared to their lengths before the oxygen therapy.

Research on Disease Risk

Telomeres are critical for maintaining genomic integrity and may be factors for age-related diseases. Laboratory studies show that telomere dysfunction or shortening is commonly acquired due process of cellular aging and tumor development. The function of telomeres is widely accepted as a buffer against tumor growth, to protect chromosome structure, and prevent the loss of vital genetic information during replication. While telomeres keep the growth and division of somatic cells in check, this can inadvertently select for rapidly dividing cells that have suffered telomere damage. As other cells divide as they are supposed to, the abnormal cells divide much quicker, outcompeting the undamaged cells, while acquiring more DNA damage that could further increase their ability to grow. This results in tumor formation.

Observational studies have found shortened telomeres in many types of experimental cancers. In addition, people with cancer have been found to possess shorter leukocyte telomeres than healthy controls. In 2011, meta-analyses suggested 1.4 to 3.0 fold increased risk of cancer for those with the shortest vs. longest telomeres.

Telomeres also exist as a possible drug target. While telomeres serve a vital function in humans, telomerase activity is generally low in most somatic cells and tissues. This provides a unique avenue for targeting eukaryotic pathogens. There are many parasitic strains of eukaryotes such as protozoans and infectious yeast that heavily rely upon telomerase activity to monitor their genome. Since normal telomerase activity in most human cells is low, targeting parasitic telomerase function might be a successful short-term treatment against pathogenic eukaryotes, without causing harm to the host.

References

1. Aubert, G., & Lansdorp, P. M. (2008). Telomeres and Aging. Physiological Reviews. https://doi.org/10.1152/physrev.00026.2007.www.prv.org5570031-9333/08 $18.00 Copyright © 2008 the American Physiological Society
2. Blackburn, E. H. (1991). Structure and function of telomeres. Nature, 350(6319), 569–573. https://doi.org/10.1038/350569a0