Who wants to live forever? The race to "cure" ageing [NZ Herald]

Could we still be living our best lives at 150 or beyond, asks Joanna Wane, and would that be such a good idea for our overburdened planet anyway?

No one really wants to live forever. Well, apart from Jeff Bezos (and Doctor Who). The Amazon founder is said to be a signed-up member of the billionaires club out to cheat death, or at least stall it significantly. After all, when you're already sending rockets on joy rides into space, is there anything money can't buy?

Bezos, the second-richest man in the world, is reported to have invested heavily in start-up Altos Labs, which aims to disrupt biological ageing by programming the entire human body to rejuvenate at a cellular level — potentially increasing life expectancy by 50 years.

Healthspan

The aim of longevity research, however, isn't to cling on to life at all costs but extend the human "healthspan" by retaining physical and mental function far beyond our current use-by date. That comes with what's known in the anti-ageing industry as a paradigm shift. Instead of pouring resources into treating specific diseases, why not focus on the root cause – the ageing process itself.

"Hundreds of billions of dollars have been spent on trying to solve Alzheimer's, Parkinson's, cancer, cardiovascular disease… and we've made progress," says Auckland biotechnologist and pharmacist Greg Macpherson. "We understand those diseases better than we ever have. But imagine if you applied that much resource into helping people stay younger for longer and taking 'luck' out of the equation."

 So just how serious is the science behind anti-ageing therapies, which are mostly still at an experimental stage? And is it ethical (or even remotely sensible) to spend billions of dollars on finding ways to significantly extend the human lifespan when our species is already consuming resources at an unsustainable rate and inducing cataclysmic climate change? As Cambridge University computer science professor Jon Crowcroft told CNBC, "It's a bit pointless living forever on a dying planet."

Put that to Macpherson and he doesn't skip a beat. With fertility rates dropping, particularly in the developed world, he thinks we're more likely to face a global crash than a crisis of overpopulation. He has faith, too, that decarbonisation and other technological breakthroughs will solve our most pressing environmental problems, while delaying the onset of age-related diseases would gain us decades of quality life.

Progress on extending longevity is already moving at such a rapid pace, he says, that even scientists are having to constantly update their worldview.

"What's unequivocal is that you CAN slow the ageing process. It's very clear now that that's possible, whereas some might have been hugely sceptical, even up to a couple of years ago. Who wants to live forever? That's definitely not the point. We only need to extend the health span by five years to have a massive and positive impact on humanity."

As for those billionaires bankrolling the quest for eternal youth, Macpherson is as realistic as anyone about their true motives. "These guys live in the future and they see an opportunity; it's the next trillion-dollar industry. So they're not just thinking about saving the planet. But they'll drag humanity along with them and we'll all live better for it. In the meantime, it's good headlines for sure."

Modern theories on what causes ageing largely fall into two overlapping camps: that it's a programmed process because living too long produces an evolutionary disadvantage, or that it's an accumulation of cellular damage. Either way, the stakes are much higher than the wounded vanity of wrinkles and grey hair. In developed countries, age is the main risk factor for cancer, neurodegeneration and cardiovascular disease.

Harnessing the Nine Hallmarks of Aging

Early this year, Macpherson released his book Harnessing the Nine Hallmarks of Aging, which distills the latest scientific research into why our bodies fail and what we can do to repair — and potentially reverse — the ravages of time. "People might think I'm completely nuts," he says. "There's no way we're going to live to 120, let alone 150, that's just bollocks. But once we didn't understand bugs and antibiotics, either."

The book draws on a 2013 paper by a group of leading European scientists outlining nine cellular and molecular markers that contribute to our decline, ranging from accumulated DNA damage to a degraded immune system. Unsurprisingly, some of it gets pretty complicated but their aim was to create a model that would help identify "pharmaceutical targets" to slow ageing and help people stay biologically young.

While it's still early days, a handful of life-extending therapies that have shown promise in animal models have progressed to clinical trials. In the US, 3000 people are taking part in the TAME (Targeting Ageing with Metformin) Trial to see whether a drug originally prescribed for pre-diabetes can delay the development or progression of heart disease, cancer and dementia.

Also headed to trial is rapamycin, which Macpherson describes as the only drug or molecule to date that has "absolutely, unequivocally" extended life in every organism it's been tested on, from mice to primates. "The final milestone is humans." Currently used to prevent organ rejection after kidney transplants, rapamycin changes the way our DNA is stored and triggers autophagy — a kind of quality-control process that removes harmful material and could potentially be harnessed for cell repair. In mice, it apparently did wonders for their skin and hair.

Researchers are exploring the gene-editing technology CRISPR for anti-ageing treatments and, in Texas, a new therapy is being trialled that adds genes to the human body without altering the existing genome.

Another relatively new area being investigated is senolytics, which targets cells that have deteriorated and are no longer able to divide. Normally, they're dispatched by the immune system but that falters as we age, leaving these troublesome zombie cells to stockpile in our tissues. A trial with older adults is being run in the US at the Mayo Clinic to evaluate the effects of Fisetin, an antioxidant with senolytic properties that's found in fruit and vegetables.

For baby boomers, that's good news. Anti-ageing therapies tend to focus less on repairing damage than preventing it in the first place. In Macpherson's book, recommended interventions start at the age of 20, although that includes the basics such as exercise, a moderate diet and learning how to manage stress. Fisetin is also being studied in Covid patients — typically in the older age bracket — to see if it helps prevent the virus from binding to their cells.

Hobamine^TM (2-HOBA) - Dr. Naji Abumrad

Back in April, legendary country singer Dolly Parton gave US$1 million for Covid research to Vanderbilt University in Nashville, helping fund what would become the Moderna vaccine. She made the donation in the name of Dr. Naji Abumrad, a professor of surgery she befriended when he was part of the team that took care of her after a minor car accident in 2013.

Abumrad met Greg Macpherson a few years ago through a mutual friend at Cambridge University. He's now among a team of international scientists on the advisory board of Macpherson's nutraceutical company, Science Research Wellness, which is focused on cellular health. Through that connection with Abumrad, a new supplement recently released in New Zealand and China contains a patented compound called 2-HOBA that's extracted from Himalayan Tartary buckwheat — only the second product in the world licensed to use it so far.

On a Zoom call from the US, Abumrad told Canvas his interest in healthy ageing began tangentially in the late 80s when he began investigating the cause of muscle wasting from protein-breakdown during illness, particularly following surgery. One of his first patients was an American football player who had both legs amputated after a car accident and lost 25kg in 10 days.

In collaboration with scientist Steve Nissen, Abumrad invented a nutraceutical HMB to support healthy muscle mass, which begins to diminish naturally from the age of 30. In the 90s, HMB was trialled to treat wasting in late-stage Aids and it's been used in medical nutrition since 2003 by athletes and patients being treated for the likes of cancer or kidney disease.

More recently, he's collaborated with the creators of 2-HOBA (marketed as Hobamine), which helps protect cells from oxidative stress. Abumrad says it's also effective as an anti-hypertensive and is soon to be trialled in early Alzheimer's disease.

At the age of 76, he's an avid cyclist and believes taking both HMB and 2-HOBA helped him recover from a bad crash last year that left him with fractured ribs and a collapsed lung. "Do I have a scientific basis for that? No. But today I cycled 26 miles and I'm not a young man anymore," he says. "I want to live a good quality of life. If not, I'd rather die quickly."

Inequity of access is one of the thorniest ethical problems of a future where it might not be out of the ordinary to celebrate your 150th birthday by knocking off a few expert Sudoku puzzles and going for a run around the block. Abumrad would like to see established nutraceutical companies create foundations to provide anti-ageing supplements to those who can't afford them, although the cost inevitably reduces over time. When he began producing HMB, it cost $1000 per kg. "Now, it's almost nothing."

Turning Back the Clock

For all the talk of being able to turn back the clock, how do you know if it's worked? On Macpherson's website, you can order a saliva DNA test that uses epigenetics to assess your biological age and theoretically see it change over time. He's met a 63-year-old doctor who's active, meditates regularly and eats a healthy diet; her biological age is 30. On the flip side, a woman in her early 40s took the test recently and was given a biological age of 67.

In principle, lifestyle changes and maybe popping a pill can help "clean" your DNA to improve performance, like polishing the scratches off a CD. I'm disappointed that Macpherson, who's 52, has only managed to knock a couple of years off his biological age — until I learn he has Crohn's, an inflammatory bowel disease.

A technology geek, he brought the first robotic dispensing machines into New Zealand and later established one of the first online pharmacies. When scientists at Otago University discovered an antioxidant molecule which is absorbed into the mitochondria and controls free radicals, Macpherson lead the  formulation of it as an anti-ageing supplement that was launched commercially in 2015.

Now out on his own, most of his anti-ageing collaborations are with scientists overseas, although he's currently working with the Cawthron Institute in Nelson to investigate the potential of bioactives in seaweed and algae to prevent sunburn, supported by a grant from the Government's Sustainable Seas fund.

A father of three, he's genuinely excited by the possibilities of an extended healthspan that would reframe what it means to be old. His own father died at 51 — younger than Macpherson is now — after contracting hepatitis C through a contaminated blood transfusion. Today, that's a curable disease. His youngest son, Jack, has already worked out that age is a mindset more than a number. He's an active member of Make It 16, a campaign to lower the voting age.

"We're not talking about spending the last 50 years of your life consuming health resources, but saying you can be 100 and as fit and healthy as you and I are right now, spending time with your grandchildren and positively contributing to society," says Macpherson, whose book is dedicated to his wife and three children.

"Even one extra day on this planet with you will be a bonus," he wrote, "but let's aim for decades."

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