Elizabeth H. Blackburn (2011) - Telomeres and Telomerase in Human Health and Disease

Elizabeth H. Blackburn (2011)

Telomeres and Telomerase in Human Health and Disease

Elizabeth H. Blackburn (2011)

Telomeres and Telomerase in Human Health and Disease

Abstract

Telomeres are the protective tips that stabilize the ends of chromosomes. The function of telomeres is to allow cells to divide while holding the genetic material intact. Telomeres contain specialized, simple repetitive DNA sequences that, together with their specifically-bound proteins, protect chromosome ends from damage. Every time cells divide, unless a process of telomere elongation intervenes, telomeres become shorter and shorter until, eventually, the cells die. Thus a telomere is analogous to a „fuse“ whose length determines the lifespan of cells – when the telomere “fuse” in cells becomes too short, either loss of cell replenishment capability, or genomic instability (with the comcomitant risk of the cell becoming cancerous) can result.
The telomere shortening process can be slowed, prevented or even reversed by the ribonucleoprotein enzyme telomerase. Telomerase rebuilds back the telomeres by adding telomeric DNA to them. By recognizing a worn-down telomere in a cell and elongating it by telomeric DNA addition, telomerase thus can effectively turn back the hands of the ticking clock that would otherwise be counting down the time to when the telomeric “fuse” will become too short and detonate. The degree of telomerase action therefore is a key factor in counteracting telomere shortening.
Telomerase is found in various human cell types. It is a unique reverse transcriptase because although, like the well-known retroviral reverse transcriptases, it has a catalytic protein, telomerase is a ribonucleic acid complex containing an essential, dedicated RNA as well as protein subunits. The RNA of telomerase contains a short sequence that is copied into the telomeric DNA, and in addition, this RNA also has evolutionarily conserved structures that are crucial to the enzymatic reaction of telomerase.
In humans, telomerase is often over-activated in malignant cancer cells, contributing to their uncontrolled growth. However, throughout human life, the telomerase in normal cells may become insufficient, because telomeres often wear down in cells, and telomere shortening in normal cells in the human body has been linked to diseases that increase with aging. In fact, through many clinical studies, telomere shortness has emerged as a potential marker for biological aging, because telomere shortness is associated with the major diseases of aging – including cardiovascular disease, cancer, diabetes, diseases of poor tissue replenishment and diseases of poor immune function, inflammation - and a higher risk of mortality.
The insights gained from the research on telomere biology are not so much related to people living longer than normal, but rather, relate to the goal of living longer in good health – that is, augmenting the so-called “health-span”. “Health-span” can be contrasted with the term “lifespan”, which only tells one how many years a person lives, but does not give information about the quality of life and health during the years a person is alive. Therefore, an important challenge is the application of this growing knowledge of telomeres and telomerase to forestalling some common diseases and improving human health.

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