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Aging and Disease    2014, Vol. 5 Issue (4) : 256-262     DOI: 10.14336/AD.2014.0500256
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Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress
Olaoluwa O Okusaga
Department of Psychiatry and Behavioral Sciences, the University of Texas Health Science Center at Houston, Texas, USA
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Abstract  

Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

Keywords Schizophrenia      accelerated aging      oxidative stress      free radicals      inflammation     
Corresponding Authors: Olaoluwa O Okusaga   
Issue Date: 04 November 2014
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Olaoluwa O Okusaga. Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress[J]. Aging and Disease, 2014, 5(4): 256-262.
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http://www.aginganddisease.org/EN/10.14336/AD.2014.0500256     OR     http://www.aginganddisease.org/EN/Y2014/V5/I4/256
Figure 1:  Inflammation and oxidative stress may reciprocally induce each other via a positive feedback loop [50]. The feedback loop involves the induction of increased production of ROS by proinflammatory cytokines (INF-γ and TNF-α) in macrophages/microglia [51] and ROS in turn enhance inflammation by activating inflammasomes, stimulating NF-κB and AP-1 as well as activating stress-activated kinases such as ERK, JNK, and p38 [55, 56]. Oxidative stress will then cause damage to cellular macromolecules including proteins, lipids and DNA leading to cell senescence which has causally been implicated in the development of age-related phenotypes. INF-γ = interferon gamma; TNF-α = tumor necrosis factor alpha; NF-κB = nuclear factor kappa B; AP-1 = activator protein 1; ERK = extracellular-signal-regulated kinase; JNK = c-Jun N-terminal kinases; Mit ETC = mitochondrial electron transport chain.
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