Telomeres and Telomerase

Telomeres are formed by tandem repeats of a DNA sequence, which is conserved throughout evolution (TTAGGG in vertebrates) and associated proteins (the so-called telomere-binding proteins or “shelterings”). Telomeres are the ends of chromosomes, which have an essential role in protecting their integrity.[1]

In organisms with cell nuclei, known as eukaryotes, chromosomes are found inside the nucleus. Most of these organisms have a set of chromosomes which come in pairs. In structural cells, each cell retains a complete set of chromosomes, in what is known as diploid form, referring to the fact the chromosomes contain two copies of each gene.

Chromosomes are highly condensed rods of Deoxyribonucleic Acid (DNA), the genetic material which contains the building blocks of life. DNA carries a specific code that gives instructions to our body on how to grow, develop and function. The instructions are organized into units called genes.Chromosomes serve as the storage for this important material, periodically dividing along with cells and replicating to make copies of the DNA they contain. Chromosomes are also very important in sexual reproduction, as they allow an organism to pass genetic material on to descendants.

The function of telomeres is to protect chromosome ends from DNA degradation activities, therefore, ensuring the proper functionality and viability of cells.

There is direct evidence for a causal relation between telomere shortening and cellular senescence [2].There is a consistent shortening of telomeres during cellular aging in and with aging of human tissues in vivo [3, 4]. Furthermore, the relation between telomere loss and senescence had been established by the finite life-span imposed on mutant yeast cells harbouring a defunct telomere maintenance system [5].

Telomeres are progressively eroded while cells are aging as the consequence of cumulative cycles of cell division to regenerate tissues. This occurs both in differentiated cells as well as in the stem cell compartments, and has been demonstrated to impair the ability of stem cells to regenerate tissues when needed.The length of telomeres at a given age is one of the best molecular markers of the degree of aging of an organism and therefore can be used to estimate its biological age.

Telomerase is an enzyme which is able to maintain telomeres and repair short telomeres by re-elongating them. To this end, telomerase add telomeric repeats "de novo" to the chromosome ends. In non-pathological conditions telomerase is expressed associated to pluripotency (early stages of embryo development), as well as in certain adult stem cell compartments. Healthy cells usually produce little or no telomerase and, as a consequence of this, they progressively shorten their telomeres associated to successive cycles of cell division, until they reach a critically short length which triggers cell death or an irreversible cell arrest known as replicative senescence If a cell divides recursively, at some point all the progeny will reach their Hayflick limit [6] which is believed to be between 50 – 70 in a person’s lifetime [7].

There is strong evidence from genetically modified mouse models that demonstrates that accumulation of critically short telomeres is sufficient to cause organ animal aging and that intervention decreases the rate of telomere shortening with age, such as forced expression of the telomere-synthesizing enzyme telomerase is also sufficient to delay aging and increase longevity.

A variety of premature aging syndromes are associated with short telomeres [8] . Thus, therapeutic strategies based on telomerase activation are envisioned as potentially important for dealing with age-related problems.

    [1] H. J. Cooke and B. A. Smith, Cold Spring Harbor Symp. Quant. Biol. LI, 213 (1986).
    [2] G. Bodnar et al., Science279, 349 (1998).
    [3] C. B. Harley et al., ibid.345, 458 (1990).
    [4] R. Allsopp et al., Proc. Natl. Acad. Sci. U.S.A.89, 10114 (1992).
    [5] H. J. Cooke and B. A. Smith, Cold Spring Harbor Symp. Quant. Biol. LI, 213 (1986).
    [6] Hayflick L, Moorhead PS 1961. Exp Cell Res 25, 3: 585–621 5 (1961).
    [7] Siegel, L ‘Are Telomeres the Key to Aging and Cancer?’ Learn. Genetics. The University of Utah. Retrieved 30 September (2013).
    [8] Blasco MA "Telomeres and human disease: ageing, cancer and beyond". Nature Reviews Genetics 6, 8: 611–22. (2005).