Aging in Schizophrenia: Perspectives on Molecular Mechanisms and a Mini-review

Evidence suggests that patients with schizophrenia (SZ) experience an acceleration of the typical aging process. However, it is unclear whether this process reflects premature aging in early life or accelerated aging in later years. Nevertheless, although the timing of accelerated aging in SZ is unclear, there is a consensus that this process is characterized by dysfunctions in immune-oxidative pathway.

It is a critical need to understand the mechanisms and trajectory of aging underlying SZ so we can target interventions earlier to the right mechanisms. This paper aims to review the recent literature regarding brain energy metabolism in aging with SZ, mainly focusing on the dysfunctions in immuno-oxidative pathway, limitations of studying aging in SZ, and perspective strategies for future studies.

Most studies reviewed in this paper point toward age-related metabolic and cognitive alterations in individuals with SZ. There are complex relationships between normative aging processes and those in SZ. However, the available data neither definitively reveal when this acceleration occurs within the life span nor attribute premature onset of aging-related changes solely to a diagnosis of SZ.

Immuno-oxidative pathway dysregulation represents convergent processes underlying the pathophysiology of both SZ and aging, contributing to synaptic dysfunction, neuronal damage, and cognitive impairment. Further research in this domain, using an innovative accelerated longitudinal design and novel, advanced neuroimaging techniques, might open new avenues for understanding common pathophysiological mechanisms and developing therapeutic interventions targeting these interconnected pathways.