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Although we naturally produce NAD, like most things, it reduces with age and the function of sirtuins become limited

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1 papers.ssrn.com Abstract Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood

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Nature 535 , 440443 (2016)