Based on their ability to prolong the lifespan of both male and female mice, Johnson’s top longevity compounds are rapamycin, taurine, and acarbose.
Over the past few years, millionaire Bryan Johnson has devised an anti-aging protocol called Blueprint that he has made available for free to everyone. However, the majority of the population does not have the riches necessary to fully follow his protocol. For instance, Johnson takes a few handfuls of prescription and non-prescription pills every day, which can get a bit pricey. Considering this, some may wonder which of these pills have the most promise for increasing one’s lifespan.
The goal of most aging biology research is to determine which interventions promote longevity — a longer life. Considering that a longer life in bad health is unappealing, researchers also focus on healthspan — years lived in good health. Keeping in mind that longevity-promoting interventions tend to also promote healthspan, Bryan Johnson’s top anti-aging pills will be chosen based on whether they can improve the user’s longevity.
The gold standard for determining the longevity potential of a given intervention is if it increases the lifespan of mammals, usually mice. This is because controlled human longevity experiments are too time-consuming and expensive to perform. Therefore, Johnson’s top anti-aging pills will be chosen based on whether they extend the lifespan of mice. Furthermore, only interventions that extend the lifespan of both female and male mice will be considered.
Rapamycin supplementation has been shown to increase mouse lifespan by 23% in males and 26% in females. In a recent X post, Johnson said he combines rapamycin (sirolimus) with metformin because this combination extends mouse lifespan further than rapamcyin alone. He also mentions that he pairs rapamycin with fats, like olive oil, to increase the drug’s bioavailability. In the post, he continues,
“We monitor safety+efficacy via body temp, sirolimus blood level, complete metabolic panel + routine biofluids, devices, imaging and fitness tests.”
Taurine is a type of amino acid (protein building block) called an amino sulfonic acid that our body synthesizes naturally. However, taurine levels tend to decline with age in humans, monkeys, and mice. Accordingly, taurine supplementation has been shown to increase mouse lifespan by 10% in females and 12% in males. In humans, low taurine levels have been associated with higher risk of mortality from heart disease. Therefore, taurine supplementation in humans could potentially replenish age-dependent losses in taurine to prolong lifespan.
The anti-diabetes medication acarbose has been shown to increase mouse lifespan by 22% in males and 5% in females. In type 2 diabetes patients, acarbose is associated with lowering the risk of all-cause mortality. Whether acarbose treatment can reduce the mortality rates of individuals without diabetes remains to be determined. Considering that acarbose counteracts high blood glucose levels, its efficacy could potentially be modulated by one’s dietary intake of carbohydrates, whereby consuming less fast-digesting carbohydrates may have similar effects.
Notably, male and female mice genetically engineered to produce high levels of hyaluronic acid (HA) — one of Johnson’s anti-aging supplements — have a longer lifespan than normal mice. However, since genetic manipulation was used in this study rather than a supplement, it is unclear whether an HA supplement would have the same effect.
Some of Johnson’s pills did not make the top three list because they were tested on inbred mouse strains or mice with genetic mutations. For example, one supplement on the list called glucosamine sulphate — used to treat arthritis — was shown to increase the lifespan of mice, but these mice harbor a genetic mutation that promotes retinal degeneration. Such mouse strains may not translate to a general human population.
Similarly, some of Johnson’s interventions may not apply to the general population because they only affect one sex. This includes alpha-ketoglutarate and spermidine, which have only been shown to increase female mouse lifespan, but not male mouse lifespan. On the other hand, vitamin C, 17α-estradiol, astaxanthin, and N-acetyl-L-cysteine (NAC) have been shown only to increase male mouse lifespan, not female mouse lifespan.
Some of the pills on Johnson’s list were shown to increase mouse lifespan in some studies but not others. For example, melatonin has been shown to increase lifespan in some studies but decreased mouse lifespan in other studies. Similarly, metformin increased mouse lifespan in one study but had no effect in another study. There are also positive and negative results for fisetin, positive and negative results for nicotinamide riboside (NR), and contradicting results for coenzyme Q10.
Other interventions were shown to increase mouse lifespan but the human data showed that the same intervention increased the risk of all-cause mortality. For example, dietary genistein was shown to increase male mouse lifespan by 10%, but high urinary genistein levels in humans are associated with higher risk of all-cause mortality. Similarly, aspirin led to an 8% increase in male mouse lifespan, but high aspirin intake is associated with higher risk of all-cause mortality in humans. Furthermore, vitamin E increased the lifespan of mice by 15%, but a dose of 400 IU/day or higher was associated with higher all-cause mortality in humans.
While mice are evolutionarily closer to humans, some studies have shown that several of Johnson’s anti-aging pills increase the lifespan of other model organisms like worms and flies. For example sulforaphane, ashwagandha, cocoa, garlic extract, ginger root extract, curcumin — the anti-aging compound in turmeric — increased worm lifespan. But extending worm lifespan does not always translate to extending mouse lifespan, as is the case with curcumin. However, high turmeric intake is associated with lower risk of all-cause mortality in humans. Additionally, the fish oil EPA has been shown to increase fly lifespan and high circulating omega-3s is associated with lower risk for all-cause mortality.
Other anti-aging compounds from Johnson’s list have been shown to lower risk of all-cause mortality but lack controlled animal research. These include extra virgin olive oil, vitamins B6 and B9, DHEA, lycopene, zeaxanthin, vitamin D, lithium, and zinc. Additionally, L-tyrosine is associated with lower risk of death from cardiovascular disease. In contrast, high iodine is associated with higher risk for all-cause mortality, and vitamin K is not associated with all-cause mortality.
Other compounds, like boron, lack anti-aging evidence. Still, others may only be specific to Johnson, such as levothyroxine (used to treat hypothyroidism) and viviscal (used for hair growth). Furthermore, supplements like pea protein, lysine, and iron may be on the list to compensate for Johnson’s vegan diet.
NMN did not make the top three list because it has not been shown to increase the lifespan of both male and female mice. However, while not yet published, Harvard’s Dr. David Sinclair and his group have presented data showing that NMN increases the lifespan of female mice. With this in mind, more studies will be necessary to determine why NMN only extends the lifespan of female mice and whether this translates to humans.