Chronic circadian rhythm disruption, particularly constant light exposure (dark deprivation), is considered a factor that accelerates aging. However, the role of mitochondrial dysfunction in this process and the possibilities of its pharmacological correction remain insufficiently understood. The aim of this study was to perform a quantitative ultrastructural assessment of the mitochondrial apparatus of rat hepatocytes during aging under constant light exposure and with exogenous melatonin supplementation. Male Wistar rats (n=480), starting from 3 months of age, were divided into three groups: control (10:14 h light/dark cycle), constant light group, and constant light group with melatonin added to drinking water (12 mg/L, 5 times/week). At 6, 12, 18, and 24 months of age, electron microscopic examination of the liver was performed with assessment of numerical density, area, perimeter, cristae count, form factor (circularity, C), and mitochondrial inner membrane coefficient (MIMC). Constant light exposure induced progressive accelerated mitochondrial aging: decreased numerical density, cristae number and length, organelle deformation, and massive hepatocyte death by 24 months. Melatonin administration prevented these alterations: the form factor was maintained at 0.80, while mitochondrial density and cristae count remained comparable to control. Chronic desynchronosis induces mitochondrial dysfunction as a key mechanism of accelerated liver aging. Exogenous melatonin exerts a potent mitochondria-protective effect, stabilizing the ultrastructure and energy apparatus of hepatocytes, which substantiates its further investigation as a geroprotector in circadian disorders.
