Telomeres, Early-Life Stress and Mental Illness

Abstract

Telomeres are structures of tandem TTAGGG repeats at the ends of chromosomes which preserve the encoding DNA by serving as a disposable brake to terminate DNA duplication during chromosome replication. In this process, the telomere itself shortens with each cell division, and can consequently be thought of as a cellular “clock” reflecting the age of a cell and the time until senescence. Telomere shortening, and changes in levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress [ELS]), and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying biomarker of stress response that crosses the brain/body distinction often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine in the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

The Cellular Sequelae of Early Stress: Focus on Aging and Mitochondria

“…These changes contribute to cellular senescence, apoptosis and cancer risk, signal increased inflammation, and ultimately contribute to organ dysfunction and risk for age-related conditions including diabetes and cardiovascular disease. Early or severe stress is associated with reductions in telomere length and maintenance, suggesting these exposures might accelerate the aging process (Ridout et al, 2015). New research supports the intriguing hypothesis that early stress may also affect mitochondrial function, further linking early stress and accelerated aging.…”

“…Telomerase, an enzyme that maintains telomere length and modulates cell signaling, gene expression, and DNA damage responses, also influences mitochondrial proliferation and function (Sahin and DePinho, 2012). Telomerase activity changes with stress and other conditions altering neuroendocrine function (Ridout et al, 2015). Glucocorticoid exposure, and associated inflammatory and oxidative stress pathway activation, is linked with telomere shortening and may be a mechanism through which early stress contributes to telomere decline (Ridout et al, 2015).…”

“…Telomerase activity changes with stress and other conditions altering neuroendocrine function (Ridout et al, 2015). Glucocorticoid exposure, and associated inflammatory and oxidative stress pathway activation, is linked with telomere shortening and may be a mechanism through which early stress contributes to telomere decline (Ridout et al, 2015). Glucocorticoid signaling is also involved in mitochondrial replication (Cai et al, 2015) and can damage mitochondria via elevating glucose levels, promoting systemic inflammation, altering gene expression in proapoptotic pathways, and hastening cellular aging (Picard et al, 2014).…”

Telomeres and Telomerase in The Aging Heart

“…(41) After each cell division, the length of the telomere shortens, and when a critical shortening is reached, the cell enters senescence or apoptosis. (42,43) Thus, TL is considered a marker of cell senescence and replicative capacity. (42,44) LTL represents the average TL across a heterogeneous population of leukocytes including monocytes, granulocytes and lymphocytes, and can serve as a biological marker of aging.…”

“…(42,43) Thus, TL is considered a marker of cell senescence and replicative capacity. (42,44) LTL represents the average TL across a heterogeneous population of leukocytes including monocytes, granulocytes and lymphocytes, and can serve as a biological marker of aging. (45) and regulation of programmed cell death.…”