Telomeres and age-related disease: how telomere biology informs clinical paradigms

Telomere(definition) length shortens with age and predicts the onset of replicative senescence(definition).Recently, short telomeres have been linked to the etiology of degenerative diseases such as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis.These disorders have recognizable clinical manifestations, and the telomere defect explains their genetics and informs the approach to their treatment.Here, I review how telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions.I also critically examine nuances of interpreting telomere length measurement in clinical studies.Understanding basic biological mechanisms holds the potential to advance clinical paradigms.The emerging impact of telomerase and telomere biology in medicine provides a clear example of this promise.Research in this area was initially sparked by fundamental questions about how genomes are protected at chromosome ends, and focused on curiosity-driven questions in maize, yeast, and protozoa (1).These highly conserved molecular mechanisms have now led to unforeseen benefits for understanding idiopathic disease and have opened a new area of translational research.Here I review the trajectory of the evolving role of telomere biology in clinical paradigms and highlight how it has become central to understanding the pathophysiology of age-dependent disorders as well as for informing new approaches to their treatment.