Boosting NAD+ for Anti-Aging: Mechanisms, Interventions, and Opportunities

A steep, age‑related drop in nicotinamide adenine dinucleotide (NAD+) now ranks among the most reproducible molecular signatures of human aging, driving metabolic slowdown, mitochondrial dysfunction, DNA‑repair deficits, chronic inflammation, and stem‑cell fatigue. Boost NAD+ for Anti‑Aging: A Multidimensional Review of Molecular, Lifestyle and Therapeutic Interventions distills findings from more than 60 peer‑reviewed studies to show how restoring NAD+ can realign these hallmarks and extend healthy lifespan. We map three converging causes of NAD+ loss—persistent PARP activation in response to accumulated DNA damage, CD38‑mediated NADase activity during “inflammaging,” and a decline in the NAMPT salvage pathway—and explain how they tip the NAD+/NADH ratio toward energetic crisis. Next, we compare the potency and safety of the main NAD+‑boosting strategies: vitamin B3 derivatives (nicotinic acid, nicotinamide), next‑generation precursors (nicotinamide riboside, nicotinamide mononucleotide, and the reduced form NRH), lifestyle modulators (caloric restriction, intermittent fasting, endurance exercise, circadian alignment), and targeted inhibitors of NAD+ consumers (CD38, SARM1). Animal studies show that strategic NAD+ repletion rejuvenates mitochondrial function, normalizes insulin signaling, lowers blood pressure, sharpens neurovascular coupling, and extends median lifespan in mice by up to 10 %. Early human trials confirm that daily supplementation raises blood and tissue NAD+ by 50–100 % and delivers measurable gains in muscle insulin sensitivity, arterial stiffness, aerobic capacity, and inflammatory profiles without serious adverse events. We also outline critical translational caveats—context‑dependent cancer risk, hormetic dosing windows, quality‑control issues in commercial supplements—and propose a data‑driven roadmap that combines NAD+ boosters with senolytics, mTOR modulation, and precision nutrition to maximize healthspan. By unifying molecular biology, pharmacology, and lifestyle science in a single narrative, this review positions NAD+ restoration as a versatile, evidence‑anchored strategy for delaying multiple age‑related diseases while enriching day‑to‑day vitality—making it essential reading for chemists, biologists, clinicians, and health‑conscious individuals seeking actionable longevity insights.