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This reaction simultaneously depletes two critically important metabolic cofactors: SAM (the universal methyl donor for hundreds of epigenetic and biosynthetic reactions) and nicotinamide (the precursor for NAD+ biosynthesis via the salvage pathway)

doi: 10.1038/nature21029 153 WheelerMAClarkICLeeHGLiZLinnerbauerMRoneJMet al

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doi: 10.1016/bs.mie.2016.09.016 12 HembergM

This is a normal part of aging but can be accelerated by long-term use of medication or an unhealthy lifestyle