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Updated: Feb 24, 2026

Developing a Rat Model for Bipolar Disorder
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Klotho dysfunction: A pathway linking the aging process to bipolar disorder?
Izabela Guimarães Barbosa1, Natalia Pessoa Rocha2, Gokay Alpak3
1Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Alfredo Balena, 190, Room 281, Santa Efigênia, Belo Horizonte, 30130-100, Brazil.
Aim:
Although accelerated aging profile has been described in bipolar disorder (BD), the biology linking BD and aging is still largely unknown. Reduced levels and/or activity of a protein named Klotho is associated with decreased life span, premature aging and occurrence of age-related diseases. Therefore, this study was designed to evaluate plasma levels of Klotho in BD patients and controls.
Methods:
Forty patients with type 1 BD and 30 controls were enrolled in this study. After clinical evaluation, peripheral blood samples were drawn and plasma levels of Klotho were measured using enzyme-linked immunosorbent assay.
Results:
Patients with BD and controls presented similar age and sex distribution. The mean ± SD length of illness was 24.00 ± 12.75 years. BD patients presented increased frequency of clinical comorbidities in comparison with controls, mainly arterial hypertension, diabetes mellitus, and hypothyroidism. Both patients with BD in remission and in mania exhibited increased plasma levels of Klotho in comparison with controls. There was no significant difference between patients in mania and patients in remission regarding the levels of Klotho.
Conclusion:
Klotho-related pathway is altered in BD. Contrary to our original hypothesis, our sample of patients with BD presented increased plasma levels of Klotho in comparison with controls. Elevated levels of Klotho in long-term BD patients may be associated with the disorder progression. Further studies are needed to better understand the role of Klotho in BD and other mood disorders.
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