Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events

Abstract

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

The relationship between neighborhood socioeconomic deprivation and telomere length: The 1999–2002 National Health and Nutrition Examination Survey

“…For example, inflammation has been heavily studied in the context of telomere dynamics (Park et al, 2015), but we saw no change after adjustment for c-reactive protein. Future analyses should consider investigating additional inflammatory pathways via biomarkers such as interleukin-6 and tissue necrosis factor alpha (Farzaneh-Far et al, 2010; Lopizzo et al, 2017; Zhang et al, 2016). The literature also highlights differences in telomere dynamics between men and women (Gardner et al, 2014).…”

“…A similar association between stress-related cortisol levels and shortened LTL was demonstrated within a small cohort of caregivers (Tomiyama et al, 2012). Transcriptomic analysis revealed an association between alterations in exposure to recent stressful events and several key signaling pathways (involving natural killer cells, interleukin-1, macrophage migration inhibitory factor (MIF)-mediated glucocorticoid and immune regulation, and interleukin-6) that may be responsible for increasing oxidative stress and the resulting damage to telomeres (Lopizzo et al, 2017). Telomeres are thought to be susceptible to oxidative stress due to their high proportion of guanine residues (Mason & Perdigones, 2013; Von Zglinicki, 2002).…”

Biological senescence risk score. A practical tool to predict biological senescence status

“…26 In pro-inflammatory states, macrophages release IL-1β and IL-6, both related to telomere shortening. 27 In the analysis of 87 of the 190 participants of The Harvard Boilermakers Longitudinal Study 28 an association was found between inflammatory parameters and the decrease in telomere length, especially with hsCRP. However, in that study, no significant relationships were found with interleukins, which may be due to the number of patients or the low variability in the plasma concentrations of these biomarkers.…”

Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?

“…In humans, cumulative inflammatory loads reflected by high levels of inflammation markers such as C-reactive protein (CRP) [27,28], fibrinogen [27], interleukin 6 (IL-6) [28,29,30], and tumor necrosis factor (TNF)-a [30] have been cross-sectionally associated with shorter TL, by a number of studies. Lin and coworkers [31] extended this evidence in a prospective study on a sample of 20 healthy mothers of children with autism (caregivers) and 19 mothers of neurotypical children (controls).…”