Regulation of Metabolic Aging Through Adenosine Mono Phosphate-Activated Protein Kinase and Mammalian Target of Rapamycin: A Comparative Study of Intermittent Fasting Variations in Obese Young Women

Abstract: Background/Objectives: Obesity accelerates metabolic aging through oxidaative stress, inflammation, and mitochondrial dysfunction. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are nutrient-sensing pathways regulating metabolism. AMPK promotes energy metabolism and autophagy, while excessive mTOR activity contributes to aging. Intermittent fasting (IF), including time-restricted feeding (TRF)�limiting food intake to a 6 h window (18:6)�and alternate-day modified fasting (ADMF)�alternating 24 h fasting (≤25% daily caloric intake) with unrestricted feeding�may improve metabolic regulation. However, their effects on AMPK, mTOR, and metabolic age remain unclear. Methods: This quasi-experimental pre-test�post-test control group study compared the TRF and ADMF on metabolic age, AMPK, and mTOR
in young obese women. Twenty-four participants (mean age: 21.29 � 1.76 years; body fat: 36.92 � 3.18%; BMI: 29.68 � 3.70 kg/m2) were initially matched by BMI and assigned to Control, TRF, and ADMF groups. A total of 4 participants (1 Control, 3 ADMF) were excluded due to outlier values, yielding final group sizes: Control (n = 7), TRF (n = 8), and ADMF (n = 5). The intervention lasted 20 days. Results: A significant decrease in AMPK levels was observed in the ADMF group (p = 0.043), while changes in the TRF and Control groups were not significant. mTOR levels showed a decreasing trend but were not statistically significant. No significant changes were found in metabolic age. Conclusions: Twenty days of intermittent fasting intervention did not significantly affect AMPK, mTOR,
or metabolic age in young obese women. TRF may more effectively enhance AMPK and reduce mTOR, while ADMF may better reduce metabolic age.