Early adversity programs induce changes that can accelerate biological aging. Using the early stress model of maternal separation (MS), we assessed oxidative, metabolic, and biochemical consequences in serum derived from middle-aged male rats to investigate systemic correlates of physiological aging in MS animals. We noted significant increases in serum corticosterone in middle-aged MS male rats, accompanied by reduced serum levels of trophic factors, brain-derived neurotrophic factor (BDNF), and insulin-like growth factor-1 (IGF1). We also found increased oxidative stress markers, such as oxidized low-density lipoprotein (Ox-LDL) in MS animals, concomitant with reduced antioxidant enzyme activity of superoxide dismutase (SOD) and catalase. The serum lipid profile analysis revealed metabolic dysregulation with increased triglyceride, total cholesterol, and LDL levels. Furthermore, mass spectrometric analysis indicated a significant increase in advanced glycation end-product (AGE) modified serum albumin peptides in middle-aged MS male rats, accompanied by enhanced expression of the precursor for AGEs, methylglyoxal (MGO), and the soluble form of the receptor for AGEs (sRAGE). Collectively, these findings suggest that the early stress of MS evokes long-lasting systemic changes that persist into middle age and reflect glyco-oxidative damage, dyslipidemia, disrupted trophic factor signaling, and enhanced accumulation of AGEs, which could contribute mechanistically to cellular and physiological aging processes.

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