Accelerated Aging in Major Depression: The Role of Nitro-Oxidative Stress

Luca, Maria; Luca, Antonina; Calandra, Carmela

doi:10.1155/2013/230797

Cited by 34 publications

(27 citation statements)

References 65 publications

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“…Major depressive disorder (MDD) has been considered a syndrome of “premature aging” (Heuser, 2002), and this notion has been reiterated in several recent reviews (Kinser and Lyon, 2013; Luca et al, 2013; Wolkowitz et al, 2011b). Further, MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging (Douillard-Guilloux et al, 2013; Koutsouleris et al, 2014).…”

Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

264

222

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Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

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Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

264

222

View full text Add to dashboard Cite

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“…On the other hand, RNS are reactive species derived from nitrogen and are classified as ions (peroxynitrite) or non-ions (nitric oxide). ROS and RNS are involved in many homeostatic processes, including the cellular response to stress, modulation of autophagy, mitochondrial function, signaling and apoptosis [117]. However, being highly reactive, ROS and RNS in certain circumstances may lead to nitro-oxidative damage to biomolecules like membrane phospholipids, sugars, DNA, and proteins, thus negatively affecting cellular function.…”

Section: O and Ns And Mitochondrial Dysfunctionmentioning

confidence: 99%

“…The potentially deleterious effects of ROS and RNS are counterbalanced by endogenous antioxidant defense systems like glutathione and melatonin, exogenous redox modulators such as vitamin C, vitamin E, zinc, coenzyme Q10, and enzymatic systems including catalase and superoxide dismutase [115,117] (Fig. 2).…”

Section: O and Ns And Mitochondrial Dysfunctionmentioning

confidence: 99%

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Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets

Carvalho¹,

Miskowiak²,

Hyphantis³

et al. 2015

CNSNDDT

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Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

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“…Otherwise, general strengthening of immunity through exercise could be helpful, accompanied by regular consumption of antioxidants (Bigley et al 2013;Luca et al 2013). …”

Section: New Strategies In Cancer Treatmentmentioning

confidence: 99%