Telomeres: the role of shortening and senescence in major depressive disorder and its therapeutic implications

Abstract

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

Loneliness, Depression, and Genetics in the Elderly: Prognostic Factors of a Worse Health Condition?

“…In a study of 238 participants, aged between 55 and 88 years, they observed a consistent association between short sleep duration, higher latency, and a faster telomere-shortening rate. Regarding the possible biochemical mechanisms that link sleep quality and telomeres, they propose inflammation, oxidative stress, cortisol secretion, and/or increased sympathetic activity [ 125 ].…”

“…For metabolic diseases, the possibility of inflammatory deregulation is raised [ 128 ]. The role of telomeres in relation to the HPA axis [ 152 , 153 ] or inflammation [ 125 ] has also been studied. In the present work, the role of telomere length along with BDNF, as an intermediary between loneliness and depression, and its relationship with a worse state of health are discussed.…”

Late Life Depression: A Narrative Review

“…In a review on the relationship between telomeres and depression, telomeres were noted to shorten with age and changes in telomerase activity were noted in peripheral blood cells and brain tissues in those with major depressive disorder [25]. Other relevant biological mechanisms were noted in this review including HPA axis activity leading to oxidative stress, inflammation, genetic and epigenetic changes.…”

Biochemical and Biophysical in Vitro Studies and Systematic Literature Review on the Antioxidant and Antiglycation Activities of Trazodone

“…Moreover, imbalance between neuroprotective (e.g., brain-derived neurotrophic factor [BDNF], progranulin, cystatin C) and neuroprogressive (e.g., nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB] and nitric oxide [NO]) factors in favor of the latter bring negative effects [3,4]. Another known cause of depression is telomerase shortening and inflammation, which increases oxidative damage at both the central (brain) and systemic (blood) level [5,6]. Polymorphisms of various genes, including those encoding enzymes of the tryptophan catabolite (TRYCAT) pathway, are also related to overproduction of reactive oxygen species (ROS) [6].…”