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Tissue homeostasis depends on regulation of metabolism in accumulating senescent cells (SnCs) with aging, and cell activation for aged tissue repair requires sufficient energy. Therapeutic advancements are potential by employing metabolic strategies for intervention. First, a disorder of arginine\u2010oxidative phosphorylation metabolism in aging skin was found, which may be the main culprit of aging. Engineered EVs (4\u2010octyl itaconate (4OI)\u2010EVs) which possess naturally abundance of\u00a0mitochondrial proteins\u00a0have been developed here. Our findings demonstrate that 4OI\u2010engineered EV (4OI\u2010EV) may accelerate the repair of aged mouse skin and diabetic mouse skin, reduce cellular senescence, and recover cell dysfunctions. After 4OI\u2010EV therapy, metabolism has been notably altered, with decreased glycolysis and increased arginine\u2010oxidative phosphorylation axis through enhanced argininosuccinate synthetase 1 (ASS1) level. 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