Telomere length – A cellular aging marker for depression and Post-traumatic Stress Disorder☆
Introduction
The name “telomere” was coined by Hermann Muller in the 1930s [1]. The term comes from the Greek words for “end” (telos) and “part” (meros). Human telomeres are regions of tandem TTAGGG repeats at chromosomal ends. At that time Barbara McClintock found that without these special end structures, chromosomes would fuse and often break upon mitosis, and the resulting chromosome instability was detrimental to cells [1]. Muller and McClintock’s pioneering studies demonstrated the basic roles of “telomeres” in protecting chromosome ends, providing chromosome stability, and ensuring faithful segregation of genetic material into daughter cells upon cell division [1]. Human telomeres protect chromosomes from degradation, fusion, and recombination [2]. The average TL is set and maintained in cells of the germline. In somatic cells, TL is heterogeneous but typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Over time, at each cell division, the telomere ends become shorter, unless this can be counteracted or reversed by the telomere-lengthening enzyme, telomerase [2], [3], [4]. Telomere shortening may increase cellular susceptibly to apoptosis and death [5]. Alexei Olovnikov and James D. Watson independently demonstrated that DNA replication machinery cannot copy chromosome ends completely and when telomeres are too short, further cell division cannot occur. Later Watson called this the “end replication problem”. Hayflick and Moorhead believed that this cellular aging phenomenon is a replicative senescence or the Halyflick limit [6]. Today, the role of telomeres in aging and many age-related disorders is increasingly being studied to better understand the aging process and fight related diseases, including mental disorders.
TL is emerging as a prognostic marker of disease risk and a robust indicator of human biological age (as distinguished from chronological age). It may represent a cumulative log of factors such as the number of cell divisions and of exposure to cytotoxic processes such as excessive oxidation and inflammation [7], [8], [9], [10], [11], [12], [13]. Thus, TL has been considered a cellular marker for age-related diseases and early death [14], [15]. Association of longer telomeres is associated with better health. In brief, the shortening of telomeres has been associated with a number of diseases, from atherosclerosis to dementia [14], [15].
Recently, knowledge of the role of telomere in diseases has advanced. In addition to the role of telomeres in cell fate and aging by adjusting the cellular response to biological stress, telomeres also play a role in response to psychological stress [16], [17]. For example, shorter telomeres have been linked to psychosocial stress, depression, and PTSD [16]. TL is significantly negatively correlated with lifetime depression. Average TL in depressed subjects who were above the median for long-term depression was 281 base pairs shorter than that in controls, corresponding to approximately 7 years of accelerated cell aging. Chronically stressed individuals (e.g., maternal caregivers of chronically ill children and family caregivers of demented individuals) showed significantly shorter TL compared to age matched controls [16], [17]. TL is negatively correlated with the duration of caregiving. Women with greater cumulative duration of caregiving stress had shorter telomeres [18]. Accelerated TL shortening in individuals with Major Depressive Disorder (MDD) and PTSD could help explain the increased medical morbidity seen in depression [5], [7], [11], [14], [19], [20] and accelerated aging in PTSD [21]. Here, we focus on the discussion of findings in studies of the relationships between TL and psychological stress-related disorder, or depression.
Section snippets
Telomeres, cellular aging, psychological stress and depression
It is found that LTL is shortened in MDD [14], [20]. LTL was significantly inversely correlated with duration of long-term depression, even after controlling for age, and was inversely correlated with both inflammation and oxidative stress in the depressed subjects. In a chronically ill population, MDD subjects had significantly shortened LTL compared to controls, with an estimated acceleration of biological cell aging of over 10 years (average telomere shortening = 660 bp) [14]. Shortening
Telomeres, cellular aging, psychological stress, and PTSD
PTSD is an anxiety disorder that develops in a minority of individuals after exposure to traumatic stress. PTSD commonly accompanies age-related diseases, such as cardiovascular, autoimmune, and neurodegenerative diseases, and early mortality [29], [41], [42], [43], [44]. PTSD is also associated with dysregulation of bodily systems that have been linked with biological aging [45], [46]. Repeated and prolonged activation of the biological stress response is a potential contributor to an
Conclusions
These studies represent direct evidence that short TL is associated with psychological stress, depression and PTSD, particularly with PTSD subjects who have a substantial history of childhood trauma. One finding demonstrated that even physically healthy young to middle-aged adults with PTSD and childhood trauma bare markers of cellular aging. However another study with a military population did not find significant difference of TL between subjects with and without childhood trauma events.
Conflict of interest
There are no conflicts of interest to declare.
Acknowledgment
We thank Berwin Yuan for helping us to edit the manuscript.
References (56)
- et al.
Tumor necrosis factor-alpha inhibits hTERT gene expression in human myeloid normal and leukemic cells
Blood
(2005) - et al.
DNA damage responses in neural cells: focus on the telomere
Neuroscience
(2007) - et al.
The serial cultivation of human diploid cell strains
Exp Cell Res
(1961) - et al.
Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging
Biol Psychiatry
(2006) - et al.
Mood disorders in the medically ill: scientific review and recommendations
Biol Psychiatry
(2005) - et al.
Depression and possible cancer risk due to oxidative DNA damage
J Psychiatr Res
(2005) - et al.
Depressive symptoms are independently correlated with lipid peroxidation in a female population: comparison with vitamins and carotenoids
J Psychosom Res
(2004) - et al.
Depressive disorders and immunity: 20 years of progress and discovery
Brain Behav Immun
(2007) - et al.
Cytokines sing the blues: inflammation and the pathogenesis of depression
Trends Immunol
(2006) - et al.
Obesity, cigarette smoking, and telomere length in women
Lancet
(2005)
Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women
Brain Behav Immun
Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder
Biol Psychiatry
Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships
Brain Behav Immun
The link between childhood trauma and depression: insights from HPA axis studies in humans
Psychoneuroendocrinology
Cell aging in relation to stress arousal and cardiovascular disease risk factors
Psychoneuroendocrinology
Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder
Biol Psychiatry
PTSD symptoms predict waking salivary cortisol levels in police officers
Psychoneuroendocrinology
Telomere, telomerase and aging
Mech Ageing Dev
Telomeres and aging
Physiol Rev
Structure and function of telomeres
Nature
Telomere states and cell fates
Nature
Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging
Nat Med
Studying telomeres in a longitudinal population based study
Front Biosci
Telomeres and human aging: facts and fibs
Sci Aging Knowledge Environ
Telomere induced senescence: end game signaling
Curr Mol Med
Psychological and metabolic stress: a recipe for accelerated cellular aging?
Hormones (Athens)
Telomeres and human somatic fitness
J Gerontol A Biol Sci Med Sci
White cell telomere length and risk of premature myocardial infarction
Arterioscler Thromb Vasc Biol
Cited by (0)
- ☆
Sources of support in the form of grants: Center for the Study of Traumatic Stress, USUHS, USA.