The telomere world and aging: Analytical challenges and future perspectives.

Telomeres, the terminal nucleoprotein structures of eukaryotic chromosomes, play pleiotropic functions in cellular and organismal aging. Telomere length (TL) varies throughout life due to the influence of genetic factors and to a complex balancing between "shortening" and "elongation" signals. Telomerase, the only enzyme that can elongate a telomeric DNA chain, and telomeric repeat-containing RNA (TERRA), a long non-coding RNA involved in looping maintenance, play key roles in TL during life. Despite recent advances in the knowledge of TL, TERRA and telomerase activity (TA) biology and their measurement techniques, the experimental and theoretical issues involved raise a number of problems that should carefully be considered by researchers approaching the "telomere world". The increasing use of such parameters - hailed as promising clinically relevant biomarkers - has failed to be paralleled by the development of automated and standardized measurement technology. Consequently, associating given TL values to specific pathological conditions involves on the one hand technological issues and on the other clinical-biological issues related to the planning of clinically relevant association studies. Addressing these issues would help avoid major biases in association studies involving TL and a number of outcomes, especially those focusing on psychological and bio-behavioral variables. The main challenge in telomere research is the development of accurate and reliable measurement methods to achieve simple and sensitive TL, TERRA, and TA detection. The discovery of the localization of telomeres and TERRA in cellular and extracellular compartments had added an additional layer of complexity to the measurement of these age-related biomarkers. Since combined analysis of TL, TERRA and TA may well provide more exhaustive clinical information than a single parameter, we feel it is important for researchers in the various fields to become familiar with their most common measurement techniques and to be aware of the respective merits and drawbacks of these approaches.