Bryan Johnson, a 48-year-old tech entrepreneur, takes approximately 50 supplements daily as part of Project Blueprint, his self-directed longevity experiment that costs roughly $2 million per year. His updated 2026 supplement regimen offers a window into which compounds researchers believe may slow aging, though most remain under investigation in humans. The stack includes notable changes: Johnson now takes NAD+ precursors six days a week instead of seven, and he has eliminated rapamycin entirely from his protocol .

What Are the Core Supplements in Johnson's Anti-Aging Protocol?

Johnson's supplement strategy centers on compounds that target specific hallmarks of aging. The foundation includes nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), both precursors to NAD+ (nicotinamide adenine dinucleotide), a molecule that naturally declines with age. Johnson takes 500 milligrams of either compound six times weekly. NAD+ plays a critical role in energy production and DNA repair, and its age-related decline correlates with fatigue, reduced metabolic function, and cognitive decline .

Beyond NAD+ boosters, Johnson's regimen includes compounds designed to address cellular waste accumulation and inflammation. Spermidine, taken at 10 milligrams daily, supports autophagy, a cellular cleanup process that slows significantly with age. Fisetin, at 200 milligrams each morning, targets senescent cells, which are dysfunctional cells that accumulate in tissues over time and contribute to systemic inflammation. Calcium alpha-ketoglutarate (Ca-AKG), taken twice daily at 1 gram per dose, has been shown in mouse studies to extend lifespan and reduce chronic inflammation .

How to Build a Science-Backed Longevity Supplement Strategy?

• Start with NAD+ Support: NMN or NR supplementation may improve physical function in older adults, according to human research. Johnson's approach of 500 mg, six days weekly, provides a model for consistent dosing without daily saturation.
• Include Senolytic Compounds: Fisetin and other senolytic agents help clear dysfunctional cells that accumulate with age. Mouse studies show fisetin extended lifespan, making it a candidate for human longevity protocols.
• Prioritize Antioxidant and Anti-Inflammatory Support: NAC (N-acetyl-L-cysteine) at 1,800 milligrams daily boosts glutathione, one of the body's most potent antioxidants. Curcumin from turmeric, taken at 1 gram with dinner and again before bed, offers anti-inflammatory and antioxidant properties that may support brain function and reduce joint pain.
• Support Mitochondrial Health: Coenzyme Q10, at 100 milligrams daily, plays a critical role in cellular energy production. Since natural levels decline with age, supplementation may support energy and endurance.
• Address Stress and Hormonal Balance: Ashwagandha, at 600 milligrams each morning, has been shown to lower cortisol, a stress-related hormone, and may improve sleep and support testosterone levels.

Johnson's full supplement list also includes vitamins D3 (2,000 IU daily), EPA omega-3 (500 mg), vitamin C (500 mg), B vitamin complex (half pill twice weekly), and multiple forms of vitamin K (K1, K2-MK4, and K2-MK7) to support bone and cardiovascular health. Additional compounds like BroccoMax (17.5 mg for sulforaphane detoxification), ginger root, garlic, and lycopene round out the anti-inflammatory and antioxidant support .

One notable change in Johnson's 2026 protocol is the elimination of rapamycin, an immunosuppressant drug that has generated significant interest in longevity research. While rapamycin shows promise in preclinical studies, Johnson's decision to remove it from his regimen reflects ongoing questions about its real-world efficacy and safety profile in healthy individuals .

What Does the Science Say About These Compounds?

The evidence supporting Johnson's supplement choices varies considerably. NMN and NR have shown promise in animal models and early human studies. Research suggests that NMN significantly improves aspects of physical function in older adults, though completed human studies remain relatively sparse. Calcium alpha-ketoglutarate has demonstrated the ability to extend lifespan and reduce chronic inflammation in mice, supporting its inclusion in longevity protocols .

Spermidine offers another example of compound-specific evidence. Beyond its role in supporting autophagy, some research suggests that higher dietary intake of spermidine reduces mortality risk in humans. Fisetin, derived from plants, has been shown in mouse studies to extend lifespan by clearing senescent cells, though human longevity trials remain limited .

Metformin, a diabetes medication included in Johnson's protocol, represents an interesting case. While typically prescribed for blood sugar management, it is also being studied for potential pro-longevity properties, though evidence in healthy individuals remains preliminary .

Beyond Supplements: The Broader Project Blueprint Framework

Johnson's supplement stack represents only one component of Project Blueprint. His comprehensive longevity protocol also includes structured protocols for diet, exercise, sleep optimization, and continuous medical monitoring. This multi-faceted approach reflects a growing recognition that anti-aging interventions work best when combined across multiple lifestyle domains. The supplement regimen, while extensive, functions as a supporting layer to these foundational lifestyle practices .

The cost and complexity of Johnson's regimen make it inaccessible to most people. However, the underlying logic of his supplement choices offers insights into which compounds researchers believe warrant investigation for human longevity. His decision to adjust his protocol annually, including dropping rapamycin, also demonstrates how longevity science remains dynamic, with new evidence continuously reshaping recommendations.

For those interested in longevity optimization, Johnson's approach suggests that evidence-based supplementation should focus on compounds with demonstrated effects on aging hallmarks: NAD+ metabolism, cellular cleanup, senescent cell clearance, mitochondrial function, and inflammation reduction. However, most of these compounds require further human research to establish optimal dosing, long-term safety, and real-world efficacy in extending human lifespan.