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categories: ["longevity"]categories: ["longevity"]tags: ["nad", "sirtuins", "supplements", "aging", "metabolism", "regulation"]tags: ["nad", "sirtuins", "supplements", "aging", "metabolism", "regulation"]summary: "Supplements such as nicotinamide riboside and NMN that raise cellular NAD+ levels, with strong pharmacokinetic evidence and weak evidence of any functional benefit."summary: "Supplements such as nicotinamide riboside and NMN that raise cellular NAD+ levels, with strong pharmacokinetic evidence and weak evidence of any functional benefit."updated: "2026-07-27"updated: "2026-10-29"humanEvidence: "Oral nicotinamide riboside reproducibly raises blood NAD+ in human trials; no trial has shown a functional benefit in healthy older adults, and the results on mitochondria and stem cell decline come from mice."humanEvidence: "Oral nicotinamide riboside reproducibly raises blood NAD+ in human trials; no trial has shown a functional benefit in healthy older adults, and the results on mitochondria and stem cell decline come from mice."access: "Nicotinamide riboside is sold freely as a dietary supplement in the United States; NMN's supplement status there is disputed and major retailers delisted it, and clinics sell intravenous NAD+ infusions direct to consumers."access: "Nicotinamide riboside is sold freely as a dietary supplement in the United States; NMN's supplement status there is disputed and major retailers delisted it, and clinics sell intravenous NAD+ infusions direct to consumers."reversibility: "reversible"reversibility: "reversible"lines 52–58 → 52–5837 unchanged lines not shown
consumed, shuttling electrons through glycolysis and the mitochondrial electron transport chain. As aconsumed, shuttling electrons through glycolysis and the mitochondrial electron transport chain. As asubstrate it is destroyed: sirtuins cleave it to remove acyl groups from proteins, PARP enzymessubstrate it is destroyed: sirtuins cleave it to remove acyl groups from proteins, PARP enzymesconsume it while responding to DNA damage, and the ectoenzyme CD38 degrades it outright. The secondconsume it while responding to DNA damage, and the ectoenzyme CD38 degrades it outright. The secondrole is what links NAD+ to aging, because the consuming enzymes are all more active in aged tissue —role is what links NAD+ to aging, because the consuming enzymes are all more active in aged tissue:more DNA damage means more PARP activity, and CD38 rises with the immune activation characteristicmore DNA damage means more PARP activity, and CD38 rises with the immune activation characteristicof [[inflammaging]] and with the accumulation of [[cellular-senescence|senescent cells]]. Fallingof [[inflammaging]] and with the accumulation of [[cellular-senescence|senescent cells]]. FallingNAD+ availability is usually placed downstream of genomic instability and upstream ofNAD+ availability is usually placed downstream of genomic instability and upstream oflines 67–73 → 67–738 unchanged lines not shown
> [!caution] The decline is less certain than it sounds> [!caution] The decline is less certain than it sounds> "NAD+ falls with age" is repeated as settled. NAD+ degrades within minutes of tissue collection,> "NAD+ falls with age" is repeated as settled. NAD+ degrades within minutes of tissue collection,> making measurement difficult, and while declines are well documented in aged mouse tissues, human> making measurement difficult, and while declines are well documented in aged mouse tissues, human> data are mixed — several studies have failed to find an age-related fall in skeletal muscle. The> data are mixed, with several studies failing to find an age-related fall in skeletal muscle. The> premise of the whole intervention is less secure than its marketing implies.> premise of the whole intervention is less secure than its marketing implies. ## Sirtuins and the resveratrol legacy## Sirtuins and the resveratrol legacyremoved, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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