Lifelong Exercise Mitigates Aging-Induced Clk2 Elevation and Attenuates Fatty Liver in Mice

Abstract

PURPOSE: This study investigated how aging regulates the expression of Clk2 (Cdc2-like kinase 2) protein and genes in the liver, and how lifelong spontaneous exercise (LSE) affects this expression. METHODS: Male C57BL/6 mice were housed under controlled conditions and divided into groups with (EXE) and without (CON) access to running wheels to investigate the effects of LSE on Clk2 expression in the liver. The mice were maintained until 99 weeks of age (Old-CON, n=7; Old-EXE, n=7), Young controls underwent the same experiment for 22 weeks and were sacrificed at the same time points as the aged mice (Young-CON, n=7; Young-EXE, n=7), and body composition was assessed using dual-energy X-ray absorptiometry. Liver tissue samples were collected 48 h after the final exercise session and Clk2 expression was analyzed. Histological evaluation of the liver was performed using hematoxylin and eosin staining, and non-alcoholic fatty liver disease (NAFLD) activity scores were calculated. RESULTS: Aged mice that underwent LSE exhibited significantly higher bone mineral content (Old-CON vs. Old-EXE, p <.05), and lower hepatic Clk2 expression compared to sedentary aged controls (Old-CON vs. Old-EXE, p<.05). LSE also led to a reduction in the NAFLD activity score (Old-CON vs. Old-EXE, p<.05), indicating less liver fat accumulation. CONCLUSIONS: Clk2 increases in the liver with aging. Additionally, LSE appears to contribute to the suppression of Clk2, thereby reducing hepatic lipid accumulation and the NAFLD activity score. However, further research is required to fully understand the direct relationship between Clk2, aging, and exercise. © 2024 Korean Society of Exercise Physiology.