Editorial

PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression

“…Nonetheless, it is possible that PBMC telomerase activity directly indexes or parallels HC telomerase activity. For example, PBMC telomerase activity and HC volume could be jointly, but independently, regulated by similar mediators, such as cortisol levels, inflammation and oxidative stress (Wolkowitz et al, 2008; Zhou et al, 2011). Further, since senescent leukocytes (e.g., CD8+CD28- T cells) with shortened telomeres and diminished telomerase activity hyper-secrete pro-inflammatory cytokines (Effros, 1997), such inflammatory mediators might, themselves, adversely impact HC volume (Arisi, 2014).…”

“…However, telomerase, a ribonucleoprotein enzyme, can rebuild and restore telomere length, preventing or delaying cell senescence (Blackburn, 1999; Calado and Young, 2009). While undetectable in most normal somatic cells, telomerase remains active in certain replicating tissues, such as male germ cells and activated lymphocytes and in stem cells, including neural stem cells residing in the dentate gyrus of the hippocampus (HC) (Mattson and Klapper, 2001; Fu et al, 2002b; Cheng et al, 2007; Zhang et al, 2007; Wolkowitz et al, 2008; Jaskelioff et al, 2011; Zhou et al, 2011). Apart from its telomere-lengthening function, telomerase (or its catalytic enzyme component, telomerase reverse transcriptase; TERT) has certain non-canonical functions that are unrelated to telomere lengthening, including (in animal models) neurotrophic, cell survival-enhancing and “antidepressant-like” properties (Zhu et al, 2000; Mattson et al, 2001; Fu et al, 2002a; Fu et al, 2002b; Kang et al, 2004; Jaskelioff et al, 2011; Li et al, 2011; Niu and Yip, 2011; Zhou et al, 2011; Liu et al, 2012).…”

Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

“…Considering the extant literature supporting the connection between psychosocial stress, depression, and telomere length (see reviews such as [21, 54, 57]), it is clear that there are interrelated pathways involved in stress and depression. Figure 2 provides a visual representation of theoretical connections between stress vulnerabilities, depression, and health outcomes, in which the physiological changes occurring in depression may be reflected in biomarkers of accelerated cellular aging [9, 21, 54, 57].…”

“… Figure 2 provides a visual representation of theoretical connections between stress vulnerabilities, depression, and health outcomes, in which the physiological changes occurring in depression may be reflected in biomarkers of accelerated cellular aging [9, 21, 54, 57]. For example, stress hormones and inflammation may be important mediators between telomere length, depression, and stress; a recent study found that high levels of pessimism, typical in depression, may be correlated with shortened leukocyte telomere length and elevated levels of IL-6 [58].…”

“…Despite the multiple limitations of the various studies and considering that it is still unclear how well telomere length may serve as a biomarker in depression, the findings are consistent with the literature which suggests telomere pathology is relevant in other chronic illnesses and chronic stress. It has been suggested that telomere shortening may be the “missing link” for understanding morbidity and mortality in depression [57]. Although the state of the science may still be relatively new in this field, TL appears to be an important novel outcome measure to incorporate into longitudinal studies.…”