Why NAD+ Declines With Age
The universal coenzyme
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme every one of your cells uses — for energy production, DNA repair, and regulation of sirtuins (the long-life genes). Tissue NAD+ levels fall ~50% between age 20 and 60. That decline tracks with many hallmarks of aging.
What consumes NAD+
NAD+ is spent by three big consumers: PARPs (DNA-damage repair enzymes), CD38 (inflammation-driven NADase), and sirtuins. All three increase with age. Age-related NAD+ decline is partly increased demand, partly reduced synthesis — restoring it tackles both sides.
Tap the NAD+ users
Each consumes NAD+ — tap to see why it matters.
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Why oral NAD+ itself doesn't work
NAD+ is a large molecule that can't cross cell membranes intact. Taking NAD+ by mouth doesn't raise tissue NAD+ — it gets digested first. This is why the supplement market moved to NAD+ PRECURSORS (NR and NMN) that ARE absorbable and get converted to NAD+ inside cells.
Exercise + sleep raise NAD+ for free
Before reaching for a supplement, two no-cost interventions raise NAD+ measurably. Exercise — particularly aerobic work — upregulates NAMPT (the rate-limiting enzyme in the NAD+ salvage pathway) by 25–30 % within weeks. Sleep restriction tanks NAD+ levels in metabolic tissues; one study showed even modest sleep loss reduced muscle NAD+ ~10 %. Caloric restriction and time-restricted eating also boost NAD+ via the same NAMPT mechanism. The supplement question only really matters once those baseline levers are dialled in.
Key Takeaway
NAD+ drops substantially with age, and the decline matters for energy, repair, and longevity signalling. Raising NAD+ is biologically attractive — but the molecule itself doesn't absorb orally, so the category is really about precursors (NR, NMN, niacin) and CD38 inhibition. Exercise + sleep + TRE raise it for free; do those before paying for precursors.