Antiaging Effects of Mannose-6-Phosphate through Enhanced Mitochondrial Function and Collagen Remodeling

Aging is closely linked to mitochondrial dysfunction and the deterioration of the extracellular matrix (ECM), especially collagen. Mannose-6-phosphate (M6P), a naturally occurring glycolytic intermediate, has gained attention as a bioactive compound with potential antiaging benefits, modulating cellular metabolism. This study investigates the role of M6P in mitochondrial activity, oxidative stress, autophagy, and collagen remodeling. In vitro experiments with human keratinocytes and dermal fibroblasts revealed that M6P treatment significantly increased ATP, NADH, and NAD⁺ levels, thereby enhancing mitochondrial function and reversing UV-induced mitochondrial damage. Additionally, M6P promoted mitophagy and reduced the level of intracellular oxidative stress by 82%, indicating its antioxidant properties. Transcriptomic analysis showed that M6P up-regulated genes are involved in collagen synthesis and DNA repair, contributing to cellular defense against UV damage. Furthermore, a clinical trial was conducted at Zhejiang Xiaoshan Hospital with 36 healthy female participants over 56 days to test the effect, which further confirmed the improvements in skin firmness, elasticity, and wrinkle reduction following the use of the M6P antiaging cream. Overall, M6P appeared as a promising candidate for antiaging, which supports mitochondrial health, reduces oxidative damage, and promotes collagen regeneration.