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
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.
- Kessing LV. Depression and the risk for dementia. Curr Opin Psychiatry. 2012;25(6):457-461. doi:10.1097/YCO.0b013e328356c368.
- Rizzo LB, Costa LG, Mansur RB, et al. The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research. Neurosci Biobehav Rev. 2014;42:157-169. doi:10.1016/j.neubiorev.2014.02.004
- Goldstein BI, Carnethon MR, Matthews KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: A scientific statement from the American Heart Association. Circulation. 2015;132:965-986. doi:10.1161/CIR.0000000000000229
- Cuthbert BN1, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 2013;11:126. doi:10.1186/1741-7015-11-126
- Lin PY, Huang YC, Hung CF. Shortened telomere length in patients with depression: a meta-analytic study. J Psychiatr Res. 2016;76:84-93. doi:10.1016/j.jpsychires.2016.01.015
- Kudlow P1, Cha DS, Carvalho AF, McIntyre RS. Nitric oxide and major depressive disorder: pathophysiology and treatment implications. Curr Mol Med. 2016;16(2):206-215.
- Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22-34. doi:10.1038/nri.2015.5
- Yamagata AS, Mansur RB, Rizzo LB, Rosenstock et al. Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders. Neurosci Biobehav Rev. 2017;72:43-49. doi:10.1016/j.neubiorev.2016.11.010
- Mansur RB, Brietzke E, McIntyre RS. Is there a “metabolic-mood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev. 2015;52:89-104. doi:10.1016/j.neubiorev.2014.12.017
- Watson GS, Craft S. Insulin resistance, inflammation, and cognition in Alzheimer’s disease: lessons for multiple sclerosis. J Neurol Sci. 2006;245:21-33.
- Wu KY, Hsiao IT, Chen CS, et al. Increased brain amyloid deposition in patients with a lifetime history of major depression: evidenced on 18F-florbetapir (AV-45/Amyvid) positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41(4):714-722.
- Houtkooper RH, ed. Sirtuins. Dordrecht, The Netherlands: Springer Science + Business Media Dordrecht; 2016.
- Cantó C, Houtkooper RH. 2016. Sirtuins and aging. In: Houtkooper RH, ed. Sirtuins. Dordrecht, The Netherlands: Springer Science + Business Media Dordrecht; 2016: 213-227.
- Guarente L. Introduction: sirtuins in aging and diseases. Methods Mol Biol. 2013;1077:3-10. doi:10.1007/978-1-62703-637-5_1
- Casey D. 2012. Elixir of immortality? Wine, resveratrol and sirtuins: an overview. J Wine Res.2012; 23(3):247-252.
- Kanal T. Resveratrol and Caloric Restriction: Sirtuins in Potential Treatments for Alzheimer’s Disease. New York: Stern College for Women, Yeshiva University; 2010.
- Kumar R, Nigam L, Singh AP, et al. Design, synthesis of allosteric peptide activator for human SIRT1 and its biological evaluation in cellular model of Alzheimer’s disease. Eur J Med Chem. 2017;127:909-916. doi:10.1016/j.ejmech.2016.11.001
- Berren MR, Hill KR, Merikle E, Gonzalez N, Santiago J. Serious mental illness and mortality rates. Psychiatr Serv. 1994;45(6):604-605.
- Gissler M, Laursen TM, Ösby U, et al. Patterns in mortality among people with severe mental disorders across birth cohorts: a register-based study of Denmark and Finland in 1982-2006. BMC Public Health. 2013; doi: 10.1186/1471-2458-13-834
- McIntyre RS, Cha DS, Jerrell JM, et al. Advancing biomarker research: utilizing ‘Big Data’ approaches for the characterization and prevention of bipolar disorder. Bipolar Disord. 2014;13:834. doi:10.1111/bdi.12162