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Does Late-Life Depression Accelerate Aging?

  • Helen Lavretsky
    Correspondence
    Send correspondence and reprint requests to Helen Lavretsky M.D., M.S., Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, 760 Westwood Plaza, Los Angeles, CA, 90024.
    Affiliations
    Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA
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Published:September 18, 2022DOI:https://doi.org/10.1016/j.jagp.2022.09.003
      Depression in older adults occurs in the context of biological aging that contributes to the clinical symptoms, biomarkers, and the course of the disease.
      • Bersani FS
      • Mellon SH
      • Reus VI
      • et al.
      Accelerated aging in serious mental disorders.
      Neurobiology of aging and late-life mental disorders share features of increased cellular senescence, inflammation, and reduced mitochondrial function. In addition, serious mental disorders (SMDs), including major depression, are associated with an increased risk of medical illnesses and premature mortality from natural causes, with lifespans up to 25 years shorter than the general population, even after controlling for suicide.
      • Bersani FS
      • Mellon SH
      • Reus VI
      • et al.
      Accelerated aging in serious mental disorders.
      Patients with late-life depression (LLD) are also at increased risk for developing somatic diseases that are typically associated with advanced age, such as cardiovascular diseases, metabolic syndrome, immune dysregulation, and dementia.
      • Bersani FS
      • Mellon SH
      • Reus VI
      • et al.
      Accelerated aging in serious mental disorders.
      The causes of this are likely multi‐factorial, including genetic predisposition, biological changes associated with early life adversity, and multiple lifestyle factors. Lifestyle factors, while important, do not fully explain the increased mortality and morbidity in these individuals, and consequently, “accelerated biological aging” is increasingly being seen as an intrinsic factor in mental disorders.
      • Lindqvist D
      • Epel ES
      • Mellon SH
      • et al.
      Psychiatric disorders and leukocyte telomere length: underlying mechanisms linking mental illness with cellular aging.
      ,
      • Darrow SM
      • Verhoeven JE
      • Revesz D
      • et al.
      The association between psychiatric disorders and telomere length: a meta-analysis involving 14,827 persons.
      This observation takes LLD and SMDs out of the realm of “mental disorders” or brain diseases, but rather points to the whole-body multisystem disorders that present with psychological symptoms.
      • Darrow SM
      • Verhoeven JE
      • Revesz D
      • et al.
      The association between psychiatric disorders and telomere length: a meta-analysis involving 14,827 persons.
      Understanding these underlying mechanisms should offer novel preventative and therapeutic opportunities to improve physical and mental health and increase the lifespan of older adults. However, it remains unclear whether these markers are causally related to depression, or simply co-exist with mental disorders. Below, we discuss several potential biomarkers that have been linked to greater morbidity- and mortality in LLD and other mental disorders, including the novel marker proposed by Mastrobattista, Diniz, and colleagues in this issue of the Journal.
      • Mastrobattista E
      • Lenze E
      • Reynolds CF
      • et al.
      Late-life depression is associated with increased levels of GDF-15, a Pro-aging mitokine.
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