Why NAD+ falls 50% by age 70.

Every cell you have runs on the same metabolic currency: nicotinamide adenine dinucleotide, NAD⁺ for short. It carries electrons through the mitochondrial chain that produces ATP. It activates the sirtuin enzymes that maintain DNA repair. It fuels PARP — the cleanup crew that fixes oxidative damage before it becomes mutation.

At age 30, tissue NAD⁺sits at a working baseline. By age 70, it’s down roughly half. That decline isn’t cosmetic. It’s the metabolic scaffolding under most of what we call “feeling older.”

Why it falls

NAD⁺isn’t a fixed reservoir. Cells build it from precursors (NR, NMN, niacin) and burn it through three primary consumers: sirtuins, PARPs, and CD38. As you age, two things happen in parallel.

• Synthesis slows. The salvage pathway that recycles NAD⁺ from nicotinamide loses efficiency. Key enzymes (NAMPT, NMNAT) decline.
• Demand rises. CD38 — an NAD⁺-degrading enzyme expressed by immune and endothelial cells — climbs steadily with age. Chronic low-grade inflammation drains the pool faster than the salvage pathway can refill it.

The net effect: a slow-motion energy deficit. Mitochondria still function, but with less headroom. Sirtuins still police the genome, but with less bandwidth. The body adapts by quietly down-regulating the things it can’t afford to run at full power — recovery, repair, cognition under load.

NAD⁺doesn’t cause aging. But aging cannot proceed without losing it.Eric Verdin, MD — Buck Institute on Aging

What the decline looks like in a person

The phenotype is recognizable because it’s how most people describe their forties and fifties:

• Energy that crashes by mid-afternoon and never fully returns.
• Workouts that take three days to recover from instead of one.
• Sleep that stays the same hours but stops feeling restorative.
• Cognitive load — context-switching, recall — that’s harder than it used to be.
• A baseline that drifts downward over years, not weeks.

None of those are diagnoses on their own. Together, they map onto a well-documented metabolic shift: less ATP per unit of mitochondrial substrate, fewer working mitochondria per cell, and more inflammatory pressure on the NAD⁺ pool.

What restoration actually does

NAD⁺ precursors — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), or NAD⁺ itself delivered IV or subcutaneously — bypass the bottlenecks in the salvage pathway. In published trials, supplementation raises blood and tissue NAD⁺ within weeks. The downstream effects people notice tend to follow the same pattern in reverse:

• Sustained afternoon energy without stimulant escalation.
• Recovery windows that compress back toward 24–36 hours.
• Sleep architecture that consolidates — fewer micro-arousals.
• A gradual lift in working-memory load capacity.

These aren’t universal and the magnitude varies. The mechanism is what’s consistent: restore the cofactor and the systems that depend on it have more headroom to do their jobs.

Where Halo fits

Halo’s NAD+ program is built around the failure mode this brief describes. We measure NAD⁺indirectly — through the downstream markers that move when the cofactor is restored — and we adjust the protocol when they don’t. Most members start with injectable NAD⁺ for the first eight weeks, then transition to oral NMN once the pool is repaired.

The decline isn’t inevitable in the way wrinkles are. It’s a downstream consequence of a single cofactor running low. That makes it one of the more tractable problems in longevity medicine — and one of the few where the intervention timeline is measured in weeks rather than years.