Telomeres and Age-Related Diseases

Abstract

Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.

Keywords: age; disease; telomere.

Figure 1

(A): Illustration of the shelterin nucleoprotein complex, which protects coding DNA and discriminates telomeres from other free DNA ends resulting from DNA damage. (B): Illustration of the closed chromatin configuration at telomeric ends. Due to protein-protein interactions and the specific binding of shelterins to telomeric DNA, double-stranded telomeric DNA is forced to fold back in a loop structure (T-loop) while the 3′ single-stranded DNA overhang is hidden inside the D-loop. The binding of shelterins to interstitial telomeric sequences (ITS) leads to the formation of interstitial telomeric loops (ITL) and establishes a closed chromatin structure that impedes the expression of subtelomeric and distal genes through telomere position effects (TPE). (C): lllustration of the open chromatin configuration at telomeric ends. Critically short telomeres can no longer maintain the compact chromatin structure. The resulting open chromatin structure facilitates the access of the translational machinery to genes that were formerly silenced by TPEs.