Telomeres and Telomerase in Human Health and Disease
Telomeres are the protective tips of chromosomes. Telomeres contain specialized, simple repetitive DNA sequences that, together with their specifically bound-proteins, stabilize chromosomes by protecting their ends from damage, thus preserving the integrity of the genome. As eukaryotic cells divide, unless a process of telomere elongation intervenes, telomeres suffer progressive attrition, causing the cells eventually to die or malfunction. This telomere shortening process can be counteracted by the ribonucleoprotein enzyme telomerase. Telomerase is a unique cellular reverse transcriptase that replenishes telomeres by adding telomeric DNA to them, thereby slowing, preventing or even reversing telomere shortening. Telomerase is found in various human cell types at widely varying levels that are highly regulated.
In humans, in normal cells throughout human life, telomerase generally appears to be insufficient, especially later in life, because telomeres often erode down, even in some stem cell types. Through extensive clinical studies, telomere shortening has been linked to several major, often co-morbid, diseases that increase with aging in human populations, and telomere attrition has a causal role in at least some of these diseases. In turn, more telomere shortening has been linked to, and can be caused by, chronic psychological stress. Telomere shortness has emerged as a potential marker for the biological aging that limits “healthspan”. An important challenge is applying the growing knowledge of telomeres and telomerase to improvements in health.
- Explain the basic molecular and cellular biological principles underlying telomere structure and function
- How telomerase acts to maintain telomeres and to describe the cellular consequences of failure to maintain telomeres in human cells
- Describe recent clinical studies that relate telomere shortness in humans to risks of chronic diseases of aging, and influences on telomere shortening including psychological stress.