Bryan Johnson, the founder of Braintree (acquired by PayPal), has become known for his intensive biohacking approach to longevity through the Blueprint supplement stack. Rather than taking a few scattered vitamins, Blueprint is a carefully selected regimen of 40+ compounds designed to address multiple hallmarks of aging simultaneously—a strategy rooted in cellular and molecular biology but still lacking robust long-term human validation. This article reviews the evidence, doses, and practical considerations for each major component of the stack.

What Is the Blueprint Stack and Why These Ingredients?

Blueprint's philosophy is that aging is not inevitable but rather driven by identifiable, addressable cellular processes: mitochondrial decline, accumulation of senescent cells, DNA damage, inflammation, and others. By targeting these pathways in parallel with evidence-backed compounds, the theory suggests, healthspan and longevity may be extended. Johnson and his team assembled the stack based on: published preclinical research, mechanistic plausibility, safety profiles in humans, and bioavailability data. The result is a tiered daily regimen split into morning and evening doses, with some compounds rotated.

Core Ingredients: NAD+ Metabolism

NMN (Nicotinamide Mononucleotide) is one of the centerpiece ingredients in Blueprint. NMN is a precursor to NAD+, a coenzyme critical for cellular energy metabolism, DNA repair, and mitochondrial function. In animal models, particularly mice and rats, NMN supplementation has been associated with improved metabolic health, exercise tolerance, and lifespan extension. However, human evidence remains limited. Small trials suggest NMN may improve muscle insulin sensitivity and aerobic capacity in older adults, but no robust human lifespan studies exist. Blueprint typically includes 250–500 mg of NMN daily. Doses in successful animal studies often scale to higher intakes in humans; current human evidence does not yet confirm longevity benefits.

Spermidine is an organic polyamine involved in cell growth, autophagy, and mitochondrial function. Spermidine is naturally present in fermented foods and whole grains. Preclinical work, especially in lower organisms and mice, has linked spermidine to lifespan extension and improved cardiovascular function. A small observational study in humans suggested dietary spermidine intake was inversely associated with cardiovascular mortality, but causation is not established. Blueprint includes spermidine at doses of 1–2 mg daily, which is within dietary intake ranges but notably concentrated. Evidence in humans remains preliminary.

NAD+ Precursors: The Broader Context

Both NMN and spermidine aim to bolster NAD+ levels and autophagy—cellular