A new wave of ‘age-reversing’ pills is upon us. Should we bite?

A scientific paradox lies at the heart of a new wave of pills promising to stave off age-related decline. To definitively prove a supplement extends human lifespan, you’d need a trial that runs for, well, a human lifespan.

Among these anti-ageing pills targeting lifespan on the cellular level is NMN, nicotinamide mononucleotide, which generates a substance known as NAD+ that repairs cellular DNA and boosts cell vitality. It’s worked wonders in mice, boosting lifespan by 20 per cent.

Are treatments promising to reverse ageing really worth the hype? Or the risk?Credit: Marija Ercegovac

NMN and other hot age-defying substances, such as resveratrol and Hobamine, have skirted the long and expensive medical drug pipeline and leapt to market as dietary supplements. Other existing drugs, including the immunosuppressant rapamycin and diabetes treatment metformin, have garnered interest outside the medical sphere as general lifespan-boosters.

So as the years of our lives tick by, what’s the state of evidence in the absence of large-scale, long-term human longevity trials? Are any of these supplements worth considering now?

Various anti-ageing nutraceutical companies, such as New Zealand-based SRW, are enticing customers to take the leap. The founder of SRW, Greg Macpherson, came to Sydney this year to speak to a room filled by influencers at the Art Gallery of NSW, decorated by boxes of their anti-ageing supplements beside arrangements of conical flasks.

Macpherson, a self-described futurist, believes our age limit is an evolutionary hangover from our mammalian ancestors scurrying around the feet of dinosaurs. Back then, it was advantageous to have short lifespans, so creatures could adapt and evolve quickly.

“It’s worked really well in terms of evolution,” he said. “But now we’re at the stage where it doesn’t serve us.”

As well as NMN, the company sells capsules containing 2-HOBA, or Hobamine, a substance drawn from Himalayan tartary buckwheat, which some believe can protect DNA against free radical damage and reduce inflammation.

Macpherson says it “should be in our water”.

Industry-funded human clinical trials found the substance reduced inflammatory molecules and boosted anti-inflammatory proteins, but the research was done on a small scale, with 33 participants and a two-week trial.

NMN has skirted the medical drug pipeline and leapt to market as dietary supplements.Credit: iStock

As for NMN, it’s a regulatory grey area. It’s under development as a drug, so it can’t be sold as a supplement off the shelf. But you can legally purchase it from overseas for personal use.

Longevity expert Dr Lindsay Wu, from the University of NSW, is no sceptic. In fact, he’s actively involved in developing NMN as a drug to treat age-related infertility in women after publishing research that found the substance restored the ability of older mice to conceive and give birth. But he cautions against jumping the gun.

“I worry that it’s got too far ahead of itself in that, if you go on to various IVF websites and Reddit forums and whatnot, people are taking the substance as part of their IVF protocol. We haven’t yet run the clinical trials to see whether it works. So that’s the caution.”

In terms of longevity, the results from human trials so far yield some promise, although the effects seem more subtle than those observed in mice.

On fertility forums, some users recommend taking NMN during IVF treatments, despite this not being official medical advice.Credit: iStock

One 12-week study found NMN improved walking speed and grip strength, although it was a tiny sample size of 20 older men. In another study of 66 people, those who took NMN with breakfast improved their walking endurance by 6.5 per cent over 60 days compared with 3.9 per cent for the placebo group. But the difference wasn’t statistically significant.

A recent review of human clinical trials into NMN concluded the supplement is safe and does hold potential as an anti-ageing agent. But it cautioned against “excessive hype surrounding NMN in the market”, especially for NMN products promising to conjure youthful skin. There is no evidence in humans it can do so and NMN can’t cross the skin barrier.

Given that so much of the evidence for longevity supplements and drugs comes from animals, there’s a program in the US dedicated to verifying the veracity of findings in mice and rats called the Interventions Testing Program (ITP).

The program takes substances purported to extend rodent life and re-tests them independently across three labs, with large and genetically diverse samples.

In these trials, lifespan-boosting promises often falter.

The allure of resveratrol, present in red wine and dark chocolate, was knocked when the ITP found no lifespan-boosting properties, for example. The same goes for metformin, a diabetes drug that attracted hype as a potential longevity-booster.

But there is one candidate that passed the ITP’s rigorous test: rapamycin. Previously used in immunosuppressant treatments for organ transplant recipients, it’s the only drug shown to consistently increase mammalian longevity. But there is a catch.

Rapamycin works by emulating what happens on the cellular level when we fast or starve and your body starts breaking down old proteins in cells, Wu says.

“So the damaged proteins, damage subcellular organelles, they get burnt up. And then when you start eating again, they get replaced with young, fresh, healthy parts of the cell.”

However, this can threaten muscle mass – decline of which is one of the critical drivers of frailty and ill health in old age.

“Rapamycin and calorie restriction actually do the exact opposite of what we want to do in older people because they both prevent protein synthesis and putting on new muscle mass.”

Whether ageing supplements are worth it is down to you. But at the very least they’re only effective when people have the fundamentals of diet and good, regular exercise in check.

It remains true the most powerful and proven intervention for anyone looking to preserve their youth does not come in a capsule; it lies in wait for you at the gym.

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