New pill considered key in the fight against ageing

The NMN pill could be key in reversing the effects of ageing. Photo / 123RF

The small pinkish pill sitting in my palm looks no more exciting than a battered Smartie. And yet it represents the culmination of centuries of ceaseless striving and quests for magical elixirs.

The Australian scientist who has developed it predicts that, in decades to come, people will look back on its creation as a moment as historically significant as the Wright brothers' first flight, reports the Daily Mail.

Apparently, it tastes like salted popcorn, but for form's sake Professor David Sinclair would rather I didn't swallow this little dose of nicotinamide mononucleotide, or NMN - although he's confident it wouldn't harm me.

On the contrary, Professor Sinclair - one of the world's leading experts on the science of ageing - believes it is the key to not only warding off the process of human ageing but even reversing it.

Now professor of genetics at Harvard Medical School, he has spent two decades investigating how to "cure" ageing and believes NMN is by far the best prospect of providing the answer.

His fountain of youth is actually a specialised variant of vitamin B3 that is found in many foods, including broccoli, cucumber and avocado, that helps our cells repair damaged DNA. The latter is believed to be a major cause of natural ageing.

In the body, NMN is converted into a related chemical called nicotinamide adenine dinucleotide (NAD), which is found in every cell of living organisms and is essential for life. NAD is crucial in fuelling the seven different genes in our body that govern ageing.

However, our NAD levels decline by about 50 per cent as we age, turning off the body's defences against ageing and age-related diseases such as cancer, diabetes, heart disease and Alzheimer's.

Experiments on mice by Professor Sinclair and his team showed that after just a week of being fed NMN dissolved in their drinking water, the cells of ageing mice were indistinguishable from those of young mice. Their muscles looked and behaved like those of a young mouse, too.

In human terms, it was the equivalent of a 60-year-old's cells and muscles transforming into those of a 20-year-old. According to the team's paper in the international journal Science, the mice suffered no negative side-effects.

Often what works brilliantly in lab mice doesn't translate to the more complex systems of humans. However, Professor Sinclair says no one has ever tried to replace our dwindling NAD before.

"NAD is a naturally occurring molecule in the body, so we're really just replenishing what's been lost over time," he says. "That's different to other strategies that have introduced a foreign molecule from a bacterium or a plant, which could have all sorts of side-effects.

"This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years from being on the market if the trials go well."

The first tests on humans will soon begin in Boston in the U.S., focusing first on safety and then on whether the treatment can actually reverse ageing in people, too.

They will be monitored closely by the U.S. space agency NASA, which is interested in using the drug during future missions to Mars to stop the accelerated ageing process that affects astronauts exposed to radiation in space.

Professor Sinclair is so convinced of his pill's safety that not only has he been taking it himself, so has his 77-year-old father.

The results certainly sound encouraging. Before he started taking a 500mg NMN pill every morning, 47-year-old Professor Sinclair had his blood tested and was told his body had a biological age of 58.

After consuming NMN for three months, he was tested again and his biological age was 32.

As for his father, he's recently been out-pacing the professor's younger brother on mountaineering expeditions in their native Australia.

"He's as vigorous as he was in his 20s and 30s, and he seems to be getting more energetic," says Professor Sinclair.

Professor Sinclair is so convinced of his pill's safety that not only has he been taking it himself, so has his 77-year-old father. Photo / 123RF

The manufacturing process of the NMN pill is complicated and expensive, and it currently costs Professor Sinclair more than $1,000 (£797) a month to buy it just for himself.

Large-scale manufacturing would bring the cost down, but he says that ultimately it won't be cheap. Of course it won't - if it lives up to the hype, then it really is the long-sought-after elixir of youth.

We each have our own image of what it might entail, and taking a pill with my Bran Flakes is certainly not what I had in mind.

I mention Ursula Andress bathing in mystical cold flames that kept her forever young and gorgeous in the 1960s film version of the H. Rider Haggard story She.

Professor Sinclair remembers it, too. Nothing like that is quite on the cards, he admits... at least not yet.

For a start, what his NMN pill cannot do is rejuvenate our exterior appearance - especially if we're already old.

The fact that Professor Sinclair, a father of three young children, still has no grey hairs and very few wrinkles seems a miracle in itself, but he suggests it isn't because of his pills.

Hair loss, grey hair and wrinkled skin are not yet reversible, he says, although if you start taking NMN young, it may delay visible ageing, as it's much easier to prevent hair loss and grey hair than reverse it.

"I don't think people will go from 80 to looking like they are 20, although a person who started taking it in their 40s could stay looking in their 40s for longer.

"What I am expecting is that their body's internal workings will function better and people will be better protected against diseases as they get older," he explains.

And yet all is not lost for Ursula Andress wannabes. Stem cell replacement - the field that could rejuvenate skin and hair - is still in its infancy, but is looking hopeful, he says.
Professor Sinclair mentions Samumed, a California research company whose backers include the venture capitalist arm of IKEA and which claims considerable success in reversing the cosmetic aspects of ageing.

By reprogramming genes to be younger, it is developing molecules that could restore hair and hair colour and remove skin wrinkles.

Another drug could even regenerate cartilage in the knees of arthritis patients.
Professor Sinclair, a molecular biologist by training who sold his first research company to British drugs giant GlaxoSmithKline for $720 million and who was in Time magazine's 2014 list of the world's 100 most influential people, is certainly not a lone voice.
There's a growing scientific consensus that ageing is not inevitable.

There's considerable disagreement, however, over to what extent the inevitable can be put off. A minority, so-called 'immortalists' - who are big on imagination but short on serious scientific credentials - believe we can avoid death indefinitely.

They include Aubrey de Grey, a British technology expert and thinker who reckons we can live for 1,000 years.

Then there's the American futurist, Ray Kurzweil, who believes that humans will eventually physically merge with artificial intelligence and transcend our biological limitations.

Finally, there's Martine Rothblatt, a transgender woman and one of America's highest-paid chief executives, who intends to grow new organs from people's DNA.

She has already commissioned a "back-up version" of her own wife - a robot which has been uploaded with the real woman's thoughts, memories and even feelings.

Ageing science is a world full of quacks and charlatans, but that hasn't stopped Silicon Valley billionaires and celebrities terrified by the thought of death from plunging vast sums into scientifically dubious projects.

Hair loss, grey hair and wrinkled skin are not yet reversible but Professor Sinclair says if you start taking NMN young, it may delay visible ageing. Photo / 123RF

A recent Los Angeles meeting to discuss the latest theories brought together the actress Goldie Hawn, pop star Moby and Google co-founder Sergey Brin, who has talked of "curing death".

More serious scientists, including Professor Sinclair, are relatively modest in their ambitions: they speak of adding at most a few extra decades to our lifespans. But what's possibly more important, they say, is improving our 'health-spans'.

For what's the use of having another 50 years to live, if you have to spend it in a wheelchair, crippled by arthritis?

Professor Sinclair has strong personal reasons for devoting his career to unlocking the secrets of ageing.

He was in the middle of studying for his PhD when his mother contracted lung cancer. And he vividly recalls his sense of outrage watching his once vibrant grandmother grow old, enfeebled and pass away.

It's a tragic story being played out in everybody's family, so why aren't we up in arms about ageing, he asks.

The answer, he knows, is because we regard ageing as inevitable. In fact, everyone believed that until scientists identified genes that control DNA repair, and therefore the ageing process, in the Nineties.

It was known that strenuous exercise and a low-calorie diet put stress on our cells, prompting them to produce more NAD and so build up their defences against the sort of damage that will age us.

But we learned that over-exercising and starving ourselves is damaging, too, especially for older people - and so scientists intensified their search for a drug that could mimic their effect.

It was Professor Sinclair who initially identified a possible candidate in resveratrol, an antioxidant found in tiny amounts in red wine and in cocoa which reversed ageing in mice.

Complicated to manufacture, difficult to administer and of limited effectiveness, resveratrol was not the miracle it had appeared. And so his search for a far more powerful substance led him to NMN.

As to what exactly it may do for us, he mentions strengthened endurance and fitness, enhanced energy, and muscles and organs such as the liver that will function more like they did when we were much younger. (If DNA damage is repaired or minimised, our organs don't have a shelf life as such.) An increased metabolism might lead to weight loss, too.

Serious ageing researchers are wary of being too specific on how many extra years their discoveries may give us, but given what it's done for mice, Professor Sinclair's estimate that NMN could buy us an extra five or ten years of healthy life sounds a little disappointing.

But it's only a start, he insists. Combined with other research that scientists are doing around the world, our age span could be extended by half again.

"I've stated before that the first person to live to 150 has already been born, and that's me projecting where we'll be [scientifically] 50 years from now," he says.

"I don't think we're going to be immortal, but there's no law of biology that says we can't live for 200 years."

What are these other areas of research? Professor Sinclair mentions two more promising drugs. One is metformin, a drug used to treat diabetes, which has been found to help some diabetics live longer than non-diabetics.

The other is rapamycin, derived from a fungus found on Easter Island in the Pacific Ocean and used to prevent organ transplant rejection. Tests have shown it suppresses the onset of cancer in mice. Both of these drugs, like NMN, trick our body into upping its defences against diseases and negative effects of ageing.

The market for an effective anti-ageing drug has been estimated at $26 billion a year.

However, Professor Sinclair and his team must first convince regulators to accept that ageing is a treatable condition - essential if they want NMN officially approved as a drug - before the floodgates can open to the millions who may want to buy it.

In the meantime, many may ask whether we want to live until we're 150 and - just as important - whether the world can cope if we do.

Critics of extending human lifespans warn that it will impose a crippling burden on healthcare and the global economy.

But Professor Sinclair believes the opposite, arguing that it's economically essential that we find a way of keeping the elderly healthy and productive.

"We're talking about people in their 90s playing tennis and educating their great-grandkids," he says.

"It'll be a totally different world where your 80s and 90s will be the equivalent of your 60s and 70s now."

And from work with laboratory mice and observations of the very elderly, it seems death when it comes will be much more rapid, possibly after a short illness such as pneumonia. Scientists call this phenomenon the "compression of morbidity".

Professor Sinclair says he thinks about the ethics of his work every day. What bothers him most is the idea that he could be sentencing people in unpleasant, unrewarding jobs to decades more misery as they struggle towards a far later retirement.

In the developed world, we're well past the Bible's approximation of the human lot of threescore years and ten - even without molecular tinkering.

Advances in medical and pharmaceutical technology, and improving lifestyles, mean that lifespans will continue to extend for much of the world's population.

The prospect of a pill to boost longevity further still is a very good reason for our children, at least, to start looking forward to that 120th birthday party.