Major depressive disorder and accelerated aging from a peripheral IGF-1 overexpression perspective.

Oleg A Levada, Alexandra S Troyan

Medical hypotheses 2020 May

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Over the past decades, data on the relationship between major depressive disorder (MDD) and accelerated aging processes were accumulated. Specific cognitive impairments, alterations in associated brain areas, a significant decrease in telomere length and expression of telomerase reverse transcriptase, oxidative and nitrosative stress, neuroinflammatory machinery, deficiency of growth factors (BDNF, IGF-1) in the brain of MDD patients resemble those that occur in aging. A decrease in the brain IGF-1 expression has been proven to disrupt mechanisms of neuroplasticity and promote cerebral inflammatory pathways, leading to morphological deterioration in the brain areas responsible for emotional and cognitive processing. From this point of view, the increase in systemic IGF-1 levels observed in most patients with MDD can be considered as a compensatory mechanism of enhancing the hypothalamic-pituitary-somatotropic axis activity in response to insufficient cerebral IGF-1 concentrations. Nevertheless, this compensatory mechanism may have a pathogenic value, improving the aging process in this patients population. This point of view has been confirmed by the evidence on the IGF-1-induced stimulation of the intracellular kinase-dependent pathways (Rho/ROCK kinase) involved in proliferation and telomere attrition in various organs, which can be considered as the underlying mechanism of aging. In line with these data, there is evidence that decreased IGF-1 signaling extends longevity in a wide range of biological species, including humans. Therefore, we hypothesized that systemic IGF-1 overexpression could be one of the pathological factors of accelerating aging in MDD patients. In this article, we analyzed data supporting this hypothesis. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Oleg A Levada, Alexandra S Troyan. Major depressive disorder and accelerated aging from a peripheral IGF-1 overexpression perspective. Medical hypotheses. 2020 May;138:109610