Heart health: New tool developed to investigate telomere length

Telomeres are protective caps at the ends of chromosomes that contain our genetic material. With each cell division, telomeres shorten. When they reach a critical length, this can lead to cell damage and age-related diseases such as Alzheimer's, cancer, and heart disease. Telomere length is considered an indicator of a person's biological age and influences the performance of heart muscle cells, known as cardiomyocytes.

A team led by Professor Christian Bär from the Institute for Molecular and Translational Therapies at MHH has developed a tool that can specifically control telomere length in stem cells. They used human induced pluripotent stem cells (hiPS cells) and edited them with the CRISPR gene-editing tool to insert a regulatory element that can specifically turn off the reading of a particular gene. This allowed the regulation of telomerase production, an enzyme that extends telomeres and delays cell aging. The results were published in the journal Cellular and Molecular Life Sciences.

Using the CRISPR ihiPSC-derived cardiomyocytes, the researchers were able to examine how telomere length affects the development of heart muscle cells and their response to stress. "We found that fully functional heart muscle cells only developed from ihiPSCs with long telomeres," reports Dr. Shambhabi Chatterjee, the lead author of the study. This discovery could have significant implications for the treatment of heart failure, as short telomeres are associated with poorer cardiomyocyte function and increased stress sensitivity.

Previous work by Professor Bär and Dr. Chatterjee showed that reactivating telomerase can help mitigate age-related diseases and protect the heart. In cell cultures and animal models, telomerase extended lifespan and had protective effects after heart attacks.

The developed tool allows for the standardized investigation of heart failure in cell cultures and provides a more reliable method for evaluating heart medications. "Previously, this required tissue samples from the heart, but these can differ greatly from person to person in terms of telomere length and are therefore only comparable to a limited extent," explains Professor Bär. With the new platform, genetically identical cardiomyocytes with different telomere lengths can be created to systematically test medications.

Professor Bär and his team hope to use their testing platform to answer important questions about the role of telomerase in heart health. Specifically, they aim to investigate whether early administration of telomerase can prevent heart failure and determine when it is most effective to counteract telomere shortening in heart muscle cells.

MEDICA-tradefair.com; Source: Hannover Medical School