Key Takeaways

No drug or supplement covered here has been shown to extend life in healthy adults. Some change biomarkers, and a few improve narrow outcomes, but those results do not establish longer life.

Rapamycin extends lifespan in several mouse experiments. The 48-week PEARL trial in healthy adults tested safety and healthspan measures, not lifespan, and did not change its visceral-fat primary outcome. [1] [2]
Oral NR and NMN raise NAD-related biomarkers. Across human trials, effects on function, metabolism, vascular measures, and other clinical outcomes are mixed or absent. No eligible outcomes trial of intravenous or intramuscular NAD itself was found in a 2026 systematic review. [3] [4]
Creatine taken with resistance training can add a small amount of lean mass and strength in older adults. Evidence for cognition is less certain, and neither result shows that creatine extends human life. [5] [6]
Metformin can blunt some exercise adaptations in some study groups. A 2026 meta-analysis did not find a uniform effect across body composition, glucose, insulin, and lipid outcomes, so the result should not be generalized to every person or used to dismiss indicated diabetes care. [7] [8] [9]
A change in NAD, an epigenetic clock, or another biomarker is not proof of fewer illnesses, better function, or longer life. Trials need outcomes that match the claim being sold. [10] [3]

What is stable

No randomized human trial has shown that any drug or supplement discussed on this page extends lifespan in healthy adults. [2] [3] [11] [12]
Mouse lifespan experiments can screen ideas, but they cannot establish a human longevity effect. The NIA Interventions Testing Program repeats candidate tests across three sites to reduce single-laboratory error. [13] [14]
Creatine has a narrow, repeatable use alongside resistance training. The added muscle and strength effects are modest and depend on training. [5]

What remains uncertain

Long-term benefits and harms of low-dose rapamycin in healthy adults remain unknown. PEARL lasted 48 weeks, analyzed 114 completers, and used a compounded product with lower exposure than planned. [2]
The clinical benefit and long-term safety of IV NAD for anti-aging use remain untested. Product quality, dose, infusion practice, and clinic oversight add separate safety questions. [3]
It remains uncertain whether small changes in muscle endurance, memory, metabolic markers, or biological-age clocks translate into less disability or longer life. [11] [6] [10]

Common questions

Does rapamycin help healthy people live longer?

That has not been shown in people. Rapamycin extends lifespan in several mouse experiments. PEARL followed healthy adults for 48 weeks and found similar adverse-event rates across groups, but it did not test lifespan and did not change the visceral-fat primary outcome. Subgroup signals for lean mass and pain need confirmation. [1] [2]

Do NMN or NR improve health, or do they only raise NAD?

They reliably raise NAD-related biomarkers. Human trials have not established a consistent improvement in glucose control, lipids, physical function, vascular function, or other clinical outcomes. One small NMN trial in 25 prediabetic women reported better muscle insulin sensitivity, but pooled NMN results have been null for several common metabolic measures. [3] [15] [4]

Is IV NAD proven for anti-aging?

No. A 2026 systematic review found no eligible outcomes trial of intravenous or intramuscular NAD itself. Evidence from oral NR or NMN cannot be transferred to an IV treatment. Infusion safety also depends on the product, dose, staff, sterile technique, monitoring, and emergency readiness. [3]

Does creatine improve longevity or mainly support training?

The best-supported use here is creatine with resistance training, where pooled trials in older adults report small added gains in lean mass and strength. Cognitive evidence is less settled. A dietary-intake cohort cannot show that creatine supplements prevent death, and no human lifespan trial has done so. [5] [6] [16]

Should a healthy adult use metformin for longevity?

Human evidence does not establish metformin as a longevity drug for healthy adults. Trials in older adults suggest that it can reduce some training adaptations, but not every outcome changed. Its established clinical role in diabetes is a separate question that depends on diagnosis, risks, benefits, and individual care. [7] [8] [9]

What does a negative mouse study mean for a supplement?

It weakens a claim that depends on the same compound, dose, and mechanism, but it does not directly test a commercial formulation or a person. The 2026 alpha-ketoglutarate result came from UM-HET3 mice, not from a human trial of Rejuvant. The right conclusion is narrower than either proof or disproof of the product. [13] [14] [10]

Does an eight-year drop in biological age mean eight extra years of life?

No. The cited Rejuvant report followed 42 customers without a randomized control group and used a commercial methylation clock. A lower clock estimate can be a research signal, but it does not equal eight added years or prove fewer illnesses, better function, or lower mortality. [10]

Did the FDA decide that NMN is safe and effective?

No. In September 2025, the FDA decided that the drug-preclusion clause did not exclude NMN from the dietary-supplement definition. That legal classification did not approve NMN for anti-aging, establish clinical benefit, or certify every product. Other dietary-supplement requirements still apply. [17]

Longevity Drugs and Supplements: Human Evidence, Limits, and Safety