With respect to the role of telomeres in disease, a remarkable twist comes from the observations that telomere reserves parallel the levels of psychological stress and risk for development of psychiatric disease48–50. In women aged 20–50 years, those with the highest levels of psychological stress had the shortest telomeres and the lowest telomerase activity in peripheral blood leukocytes, and showed the highest levels of oxidative stress49. The connection is particularly intriguing because individuals subject to chronic psychological stress show a shortened lifespan and more rapid onset of diseases typically associated with ageing, such as cardiovascular disease and accelerated ageing of the immune system50. The activation of autonomic and neuroendocrine systems, and the subsequent glucocorticoid-driven increase in ROS, might underlie accelerated telomere erosion and damage telomeres directly51,52. More speculatively, such damaged telomeres may not be repaired efficiently, owing to low levels of telomerase activity and an inherent shielding of telomeres from DNA repair machinery. As such, damaged telomeres may provide a reservoir of persistent DNA damage signals and consequent sustained p53 activation with senescent sequelae.
