- Testing metformin in mice has not extended lifespan, however, whether these findings apply to humans remains an open question.
- Resveratrol, administered in varying doses, does not extend mouse lifespan; however, a lack of understanding regarding the most effective dosage could hinder its potential lifespan-extending benefits.
- Mouse studies testing NR have not shown that it extends lifespan, however, Rich Miller says that future testing will reveal whether combining NR with other compounds enhances longevity.
In a YouTube segment, Peter Attia, M.D. interviewed Rich Miller, M.D., Ph.D., the Director of the Center for Aging Research at the University of Michigan. Dr. Rich Miller is also one of the architects of the Interventions Testing Program (ITP), a consortium of researchers that tests whether certain compounds extend mouse lifespan. Along the lines of his work with the ITP, Rich Miller says that three compounds that have received lots of anti-aging hype, resveratrol, metformin, and NR, do not extend mouse lifespan on their own.
Has Metformin Been Over-Hyped?
“The fact that something fails in mice doesn’t mean it’s going to fail in people,” says Rich Miller. “Testing people is going to be much harder. It’s easier to sell stuff that’s untested, but in principle, one could actually test it in people and see if it does anything good.”
All the same, the ITP’s testing of compounds on mouse lifespan gives some of the best indications we have of whether these molecules influence longevity. Along those lines, one of the compounds the ITP has found to be ineffective for lifespan extension is the anti-diabetes drug metformin.
Metformin has sensibly been labeled an anti-aging drug for people, according to Miller. He goes on to say that it is very safe, and a case can be made that it postpones aspects of aging in people. Metformin, however, does not seem to work in mice.
Despite its failures in extending mouse lifespan in ITP studies and since mouse studies do not always translate to humans, researchers have set up a trial to find whether metformin extends human lifespan. Called the Targeting Aging with Metformin (TAME) study, this trial aims to find whether metformin reduces the age-related incidence of conditions like heart disease, cancer, and dementia along with mortality in adults who do not have diabetes. Nonetheless, even though this study could produce tantalizing results, it has not yet been started due to a lack of funding.
Resveratrol Fails to Extend Mouse Lifespan
Resveratrol was hyped for many years, according to Miller. Resveratrol can be found in red wine, and it purportedly activates sirtuins, which are proteins thought to play key roles in activating pro-longevity genes. Miller says, though, that none of these ideas about resveratrol are correct. In fact, its status as a sirtuin activator has been questioned by very serious and skilled biochemists. Furthermore, in order to get enough resveratrol to gain its purported benefits, one would have to consume about 30 bottles of red wine within a short period, according to Miller.
Importantly, resveratrol given at a number of different doses failed to extend mouse lifespan. Miller goes on to say that many other groups have also shown that resveratrol fails to extend lifespan in several different strains of mice. As such, he says that the collective evidence does not support the idea that resveratrol slows aging in mice.
“People are very easy to fool,” says Miller. “People are very very gullible.” These words go along with his criticism of people’s willingness to buy resveratrol-containing supplements.
NR Mixed with Other Compounds May Extend Lifespan
NR is a precursor to and has been shown to increase levels of the molecule nicotinamide adenine dinucleotide (NAD+), a molecule that every cell in our bodies use for energy production, among other functions. Although Miller says that NR failed to increase mouse lifespan in ITP studies, he says that some other “trick,” such as adding an enzyme that reduces NR or NAD+ degradation, may in fact extend mouse lifespan. In that regard, he says that the ITP plans to test NR with one other compound, which he did not identify in the interview.
Moreover, Miller says that other researchers have encouraged him and the ITP to test another NAD+ precursor called NMN, which is perhaps more bioavailable — a higher percentage ingested enters blood circulation. Along those lines, Miller says that he and the ITP are in negotiations with a private vendor to attain enough NMN to test its effects on mouse lifespan in the near future.
Mouse Studies Do Not Always Translate to Humans
“It could be true that it doesn’t work in mice but it works in people,” Miller adds.
In this regard, the ITP’s findings must be taken with a grain of salt, meaning that mouse studies do not always provide the full story of potential benefits that people attain from these compounds. While resveratrol, metformin, and NR on their own have failed to extend mouse lifespan, they could confer advantages such as allowing people to increase the number of disease-free years that they live. Moreover, only human trials testing the effects of these molecules on lifespan can give more convincing evidence of whether they extend human lifespan, although such trials are frequently cost-prohibitive.
An interesting caveat that Miller brought up was that the ITP plans to test NR with another compound, which a prominent biochemist says extends mouse lifespan, according to Miller. Miller admitted he believes increasing NAD+ with precursors like NMN or NR holds potential to slow aging even if the research does not currently reflect that belief. Along those same lines, if the negotiations with the unspecified private vendor work out, the ITP will soon test whether NMN extends mouse lifespan. Since NR on its own does not extend mouse lifespan, if NMN alone enhances longevity, these findings would support NMN’s superiority over other NAD+ precursors like NR.