Systemic Telomere Length and Aging

Telomeres represent essential structure for genome stability, since their role is to protect the extremities of linear chromosomes from degradation and recombination. Furthermore, they also participate in the nuclear architecture, as well as in the meiosis-specific genome recombination and reorganization.

Telomere length is the result of the equilibrium between shortening and lengthening mechanisms, and in many different organisms there is a decrease in length with increasing age. This suggests that the activity of the enzyme telomerase (which is a specialized reverse transcriptase) is limiting, even in stem cell compartments.

Telomeres and aging

Aging is usually defined as the progressive functional loss of tissue function that eventually leads to death. This can stem from diminished function or complete loss of postmitotic cells, but also from the inability of stem cells to adequately sustain replication and cell division.

One of the best-described intrinsic events taking place in the cell which is associated with aging is the progressive shortening of telomeres. Most tissues and organs in humans show substantial telomere shortening during ageing process, including peripheral blood cells, vascular endothelial cells, hepatocytes, kidney epithelium, muscle cells and many others.

Since telomere shortening can trigger cell senescence in vitro, current theory is that telomere shortening represents a dominant cause of tissue dysfunction that characterizes the aging process in vivo, telomere length is increasingly being accepted as a valid biomarker of aging. For that purpose, peripheral blood leukocyte telomere length is a best way to assess systemic telomere length.

The rate of telomere shortening with age is different between men and women, and can be influenced by different factors that accelerate aging and the risk of premature death by negatively affecting telomere length – most notably stress, smoking, lack of exercise, obesity and socioeconomic status.

It must be noted that many studies evaluating the connection of telomere length and age have very low number of subjects with exceptional longevity. Also, the entire aging process cannot be explained merely by telomere shortening, and the direct evidence linking replicative senescence and human aging remains controversial.

Telomeres and age-associated disease

Research has shown that telomere shortening occurs not only during normal aging, but also during a myriad of age-related pathological conditions such as cardiovascular diseases or cancer. Moreover, premature aging syndromes (such as Werner syndrome) are also characterized by accelerated shortening of telomeres.

Mutations in telomerase genes that accelerate telomere shortening can give rise to several human syndromes such as dyskeratosis congenita, idiopathic pulmonary fibrosis and aplastic anemia. On the other hand, aforementioned premature aging syndromes are usually linked to the mutations in different DNA repair proteins.

Studies have shown that elevated risk from cardiovascular diseases is linked to the high rate of telomere attrition, and telomere length alone is considered an independent risk predictor for stroke and myocardial infarction. In addition, endothelial cells associated with the atherosclerotic plaque have shorter telomeres in comparison to endothelial cells from subjects without coronary artery disease.

The discovery of the exact role of telomeres and telomerase in aging and disease has been crucial for developing appropriate therapeutic strategies. Interventions should be designed to target cell types that normally divide to maintain organ homeostasis – most notably stem cells.

Further Reading

• All Telomere Content
• What are Telomeres?
• Telomere Shortening
• Telomeres and Cancer
• Telomere Function

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.