Klotho levels in chronic overwork stress: An animal model study

Abstract

Background: Sudden death from overwork, or “karoshi,” is poorly understood, particularly regarding its underlying pathogenesis. Forensic studies have shown myocardial interstitial fibrosis in patients with a history of prolonged overwork, but the mechanisms connecting overwork to cardiovascular disorders remain unclear. Objective: This study investigates Klotho expression in the heart and kidney of an overworked rat model. We hypothesize that overwork alters Klotho levels, contributing to myocardial fibrosis and cardiovascular dysfunction. Methods: An overworked rat model (n = 5) was established using the Forced Swim Test, which involved 30 consecutive days of forced swimming. The expression of Klotho was assessed in myocardial and renal tissues and serum using Western blot, immunohistochemistry, and Enzyme-Linked Immunosorbent Assay (ELISA). Masson's staining was performed to evaluate myocardial interstitial fibrosis, and statistical analyses were conducted to compare the differences between the overworked and control (n = 5) groups. Results: We found a significant decrease in Klotho expression in myocardial and renal tissues and serum in the overworked group compared to controls. Overworked rats exhibited notable myocardial fibrosis, while kidney fibrosis was minimal. These results suggest that overwork reduces Klotho levels and induces myocardial fibrosis. Conclusions: Our findings indicate that overwork reduces Klotho expression and promotes myocardial fibrosis, shedding light on the pathophysiology of karoshi and related cardiovascular diseases. Further research is needed to explore potential therapeutic interventions targeting Klotho to prevent overwork-induced cardiovascular damage.