Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Abstract

Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

Leukocyte telomere length: Effects of schizophrenia, age, and gender

“…This has led to a suggestion that schizophrenia is associated with accelerated biological aging (Anthes, 2014;Dawes et al, 2011;Kirkpatrick et al, 2008;Kochunov et al, 2013;Koutsouleris et al, 2014;Lindqvist et al, 2015;Okusaga, 2014;Schnack et al, 2016;Shivakumar et al, 2014). Whereas men have overall higher death rates than women, mortality ratios in schizophrenia (standardized to the general population with respect to age, race/ethnicity and geographic region) are higher in women than in men with schizophrenia, with cardiovascular disease being a leading cause of premature death in both genders (Olfson et al, 2015).…”

“…Whereas chronological age is measured in calendar years, biological age is defined physiologically and is often more closely associated with disease processes (Cawthon et al, 2003;Epel, 2009;Lindqvist et al, 2015). Accelerated biological aging occurs when biological age outpaces chronological age (Lindqvist et al, 2015).…”

“…Accelerated biological aging occurs when biological age outpaces chronological age (Lindqvist et al, 2015). One marker of biological age is telomere length (TL), often measured in leukocytes (LTL), since it progressively declines with age and may be inversely related to diseases of aging and mortality (Bojesen, 2013;Cawthon et al, 2003;Mather et al, 2011;Muezzinler et al, 2013;Svensson et al, 2014).…”

“…One marker of biological age is telomere length (TL), often measured in leukocytes (LTL), since it progressively declines with age and may be inversely related to diseases of aging and mortality (Bojesen, 2013;Cawthon et al, 2003;Mather et al, 2011;Muezzinler et al, 2013;Svensson et al, 2014). However, peak LTL (shortly after birth), the age at which a decline begins, the rate of decline, and when death interrupts the process, vary among individuals (Svensson et al, 2014), suggesting important interindividual differences in the rates of biological aging (Epel, 2012;Lindqvist et al, 2015;Muezzinler et al, 2013). Variability in telomere length among people of the same chronological age raises the possibility that telomere shortening is potentially modifiable (Bojesen, 2013).…”

“…Telomeres shorten with advancing age (Muezzinler et al, 2013) and are generally shorter in men than in women (Gardner et al, 2014). Telomeres also shorten with repeated mitosis in somatic cells, with replication-and nuclease-associated telomeric DNA damage, and with exposure to oxidative stress, certain cytotoxins, inflammation, and possibly stress hormones (Effros, 2011;Epel et al, 2004;Lindqvist et al, 2015;von Zglinicki, 2002;Wolkowitz et al, 2011). Among the most important lifestyle-and experience-related factors that may impinge on LTL are stress (Epel, 2009;Epel et al, 2004), tobacco use (Babizhayev et al, 2011), exercise (Puterman et al, 2010); and diet (Epel, 2009;Freitas-Simoes et al, 2016), as well certain medical risk factors, such as visceral adiposity (Epel, 2009) (but see (Diaz et al, 2010)), metabolic stress (Epel, 2009) and certain chronic viral infections (e.g., cytomegalovirus) (Effros, 2011).…”