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Maiese (2023), in Frontiers in Immunology , directly linked low NAD+ to oxidative stress, free radical accumulation, and age-related conditions including diabetes, neurodegenerative disease, and vascular damage
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The review confirmed that NNMT-mediated NAD+ depletion impairs mitochondrial function, SIRT activity (particularly SIRT1 and SIRT3), redox balance, and energy metabolism, creating conditions relevant to cardiovascular disease research models
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