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This age-related NAD+ decline correlates with numerous hallmarks of aging: Mitochondrial dysfunction and reduced ATP production Genomic instability and impaired DNA repair Cellular senescence (zombie cells that won't die) Metabolic slowdown and insulin resistance Neurodegeneration and cognitive decline Decreased muscle strength and endurance The mechanisms driving NAD+ decline include: Increased consumption by DNA repair enzymes (PARPs) and CD38 (NAD+-degrading enzyme that increases with age and inflammation) Decreased synthesis from precursors due to reduced enzyme activity Reduced efficiency of the salvage pathway that recycles nicotinamide back to NAD+ "NAD+ levels decline with age in multiple tissues, and this decline appears to contribute to numerous age-related pathologies
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PubMed PMID: 26597770
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