Stress and immunosenescence: The role of telomerase.

Chronic stress is associated with the accelerated aging of the immune system and represents a potent risk factor for the development and progression of a wide range of physical and mental disorders. The elucidation of molecular pathways and mechanisms underlying the link between stress and cellular aging is an area of considerable interest and investigation. In this context, telomere biology has emerged as a particularly attractive candidate mechanism. Several studies have linked immune cell telomere length with stress-related conditions and states, and also with several physical and mental disorders. Because the cellular reverse transcriptase enzyme telomerase is the primary regulator of telomere length (by adding telomeric DNA to telomeres and thereby attenuating telomere shortening), the understanding of its regulation and regulatory functions constitutes a prime target for developing strategies to prevent, attenuate or reverse the adverse consequences of immune system aging (immunosenescence). In this review we provide an overview of the mechanistic pathways linking telomerase with stress and cellular aging, with an emphasis on the immune system. We summarize and synthesize the current state of the literature on immune cell telomerase in different stress- and aging-related disease states and provide recommendations for future research directions.