Chronic Light-Induced Desynchronosis as a Model of Accelerated Metabolic Aging in Rats: Prevention and Correction by Exogenous Melatonin

Background: Chronic exposure to artificial light at night (light pollution) causes circadian desynchronosis and melatonin deficiency, which is considered an independent driver of metabolic disorders and accelerated aging. However, the long-term effects of chronic desynchronosis on systemic metabolism and liver structure throughout the life cycle, as well as the potential of preventive melatonin administration, remain poorly understood. Objective: To evaluate the effects of chronic dark deprivation and prevention of metabolic disorders by exogenous melatonin on plasma melatonin levels, metabolic profile, liver function, and morphological changes in rats over a 24-month experiment. Methods: A 24-month experiment was conducted on 360 male Wistar rats divided into three groups: control (standard 10:14 h light/dark photoperiod), dark deprivation (DD, constant illumination), and correction (DD+Mel, constant illumination + melatonin 10 mg/kg five times per week). Animals were sacrificed at 6, 12, 18, and 24 months. Plasma melatonin was assessed by ELISA. Biochemical parameters (ALT, AST, LDH, total protein, albumin, bilirubin, glucose, triglycerides, and cholesterol), body weight, liver weight, relative liver weight, and histological parameters (steatosis, fibrosis, nuclear area, nuclear/cytoplasmic ratio, and binucleated hepatocytes) were analyzed. Results: In the DD group, a persistent progressive melatonin deficiency was detected (5.1-fold decrease by 6 months, p < 0.0005), accompanied by hypertriglyceridemia (Cohen’s d = 6.40), hypercholesterolemia (d = 4.59), biphasic dysglycemia (hypoglycemia followed by hyperglycemia), elevated ALT and AST activity (d = 2.60 and 2.46, respectively), hypoproteinemia (d = 5.33), hypoalbuminemia (d = 3.34), and hyperbilirubinemia (d = 3.22–4.37), as well as progressive steatosis (2.8 ± 0.3 points, d = 7.20) and pericellular fibrosis (1.8 ± 0.4 points, d = 4.50). In the DD group, a decrease in relative liver weight during the first 12 months was observed (metabolic disproportion, d = 2.31), reflecting disproportionate body weight gain. In the DD+Mel group, exogenous melatonin restored the biochemical parameters to values that did not differ statistically from the control values (Cohen’s d < 0.2 for most parameters), prevented steatosis (0.8 ± 0.3 points, d = 0.80) and fibrosis (0 points), increased relative liver weight by 24 months (3.83 ± 0.49 vs. 3.27 ± 0.029 in the control, d = 1.60), and increased the hepatocyte nuclear area (58.4 ± 4.1 vs. 48.6 ± 3.8 μm2, d = 2.32). Conclusions: Chronic desynchronosis induced by constant illumination leads to persistent melatonin deficiency and complex metabolic and structural liver disturbances modeling accelerated aging. Exogenous melatonin (10 mg/kg five times per week) exhibits pronounced geroprotective, hepatoprotective, and antifibrotic effects, normalizing all biochemical parameters and preventing age-related liver involution.