Reductions in sirtuin activity may contribute to senescence and may also be a pathogenetic nexus bridging mood disorders with other age-related conditions such as insulin resistance. Sirtuin activation has been shown to reduce immobility in behavioral models of depression and has been hypothesized to be potentially brain-therapeutic. Well-known sirtuin activators include caloric restriction and resveratrol, which is present in many red wines.15,16 It is interesting that in animal studies caloric restriction is associated with greater longevity. There are several pharmacological activators currently being studied.17

The most staggering and ignominious example of how premature aging may be a critical process in mood disorders is seen in mortality studies. It has been variably reported that individuals with mood disorders lose approximately 10 to 25 years of life when compared with individuals in the general population.18 Moreover, the yawning gap between lifespan reported in individuals with mood disorders and other serious mental illnesses has been expanding during the past 2 decades. The most frequent specific cause of premature mortality is cardiovascular disease, with other medical conditions that are overrepresented also contributing to the process.19


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Mood disorders are heterogeneous in phenomenology, pathoetiology, illness trajectory, and response to treatment. It is unlikely that premature aging affects all individuals with this condition. It is more likely that a subpopulation of individuals with mood disorders exhibit evidence of premature aging, leaving them at risk for age-related morbidity and mortality. We hope that the availability of large data and bioinformatics capabilities will enable the quantification and robust prediction of which individuals are more susceptible to a more progressive illness course and risk for age-related conditions.20

Until empirical data are available, it seems prudent to educate all individuals with mood disorders about the possible risk of disparate age-related medical conditions  such as cardiovascular disease and diabetes. Traditional risk factors should be screened for and modified as the neuroscience community attempts to identify precise mechanistic pathways that are putatively age-related. There is much we can do clinically to improve both the duration of life as well as healthy life (life lived without medical morbidity) by providing integrated and best practices care.

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