About 3,500 years ago a Sumerian scraped the tale of the young King Gilgamesh’s desire to live forever onto tablets of clay. Since then, it’s been a trope that refuses to die. The Fountain of Youth (sought by Spanish explorer Juan Ponce De Leon to help him “keep up” with his lover), the Holy Grail, Gulliver’s Travels’ struldbrugs, Kristen Stewart’s lust for vampiric foreverness with Robert Pattinson in the Twilight films – the list is nearly as long as immortality itself.

Possibly buoyed by such inspirational stories, scientists have strained to achieve temporal elasticity by halting, reversing or at least slowing the ageing process. And for good reason – according to Global Industry Analysts, the anti-ageing product industry is set to reach a staggering $291.9bn by 2015.

Arlene Weintraub, author of Selling the Fountain of Youth, says that this extraordinary surge is largely down to the baby boomers: “They don’t want to age like their parents age, being frail and having that kind of slow decline to the nursing home. This generation really wants to avoid that.”

In the past few years a clutch of speculative start-ups have edged onto the radar, boasting genuine scientific clout and eschewing the usual supplements and cosmetics. In 2008, GlaxoSmithKline shelled out $720m to buy Sirtis Pharmaceuticals, a company touting resveratrol, a compound found in red grape skins that extended the lifespan of obese lab rats (though the project never reached fruition). One of the more vocal proponents of anti-ageing research is the maverick venture capitalist Peter Thiel (of Facebook and Paypal fame), who proffers funds through his innovation- catalysing Thiel Foundation.

Polymathic futurist, legendary inventor and all-round cerebral mindbender Ray Kurzweil, meanwhile, pushes the debate into hyperspace, regularly hitting the headlines for his radical theory of accelerated technological returns wherein we are reprogramming the underlying information processes of biology and forging a future where man and machine might become one. Apparently, we could even back up our bodies and brains should we “get hit by the proverbial bus”.

“These advances are accelerating,” he says phlegmatically. “Ultimately, we will become a hybrid of biological bodies and brains with non-biological augmentations”

Others remain sceptical. “The fundamental process of ageing is the result of the failure of repair processes to keep up with the inevitable loss of molecular structure as a result of the second law of thermodynamics,” says Leonard Hayflick, professor of anatomy at the University of California, San Francisco, School of Medicine, founding member of the council of the National Institute on Aging, and one of the godfathers of anti-ageing science thanks to his discovery that human cells divide for a limited number of times in vitro (the Hayflick limit). “There is no known process that will slow or stop the ageing process in humans. Period. It has never been done. And there is no evidence that it will be done.”

Deep in the heart of Reno, Nevada, Bill Andrews is hoping to change all that. “Cure ageing or die trying,” screams the slogan of his biotech company Sierra Sciences; part yuk-yuk bumper sticker, part deranged battle cry, but 100% serious in intent. Andrews, 59, is a man prone to obsession. One of America’s more accomplished ultra- marathon runners (top distance: 135 miles across Death Valley, California), he can more often than not be found contorting his 6ft 3in frame atop a chest of drawers for an overnight stay in the office. “There was a point when the only time I left work was to go running,” he confides. “I would wear my running clothes at work and go running while I was waiting for tests to run. Sometimes I’d sweat into the sample and have to do it all again.”

So far, so crazy, yet Andrews is far from being another whackjob in the all-too frequently loopy anti-ageing business. As a leading research scientist and molecular biologist, he is as respected as he is divisive. Back in the 1990s, he directed a team of researchers at Bay Area biotech firm Geron to identify the human telomerase gene.

In biological terms, this was unequivocally a Big Deal.

Telomerase is an enzyme that sustains the ends of cell chromosomes known as telomeres. Each time a cell divides, telomeres shorten over and over again until the cell can no longer replicate. Provided we live long enough, the anatomical nuts and bolts reliant on cell division – from organs to immune system – start breaking down.

Sierra Sciences hopes to curb the pace of our inevitable death spiral by inducing telomerase production, an impact that is not only likely to be felt among those dreading the Grim Reaper; Andrews claims telomeres can affect practically every disease known to mankind.

There has been fervent interest in telomeres’ anti- ageing potential since biochemist Elizabeth Blackburn discovered the telomerase enzyme in a pond-scum protozoan, winning a Nobel Prize for her troubles. Then last year, things got really interesting when Harvard University researcher Ron DePinho published a study in Nature dramatically highlighting the potential merits of telomerase activation. DePinho was able to switch off telomerase in a mouse and restore it using a synthetic oestrogen drug. He found that mice with inactive telomerase genes displayed all manner of geriatric attributes – wrinkles, dodgy intestines, reduced brain function – but when reactivated, they reverted to youthful exuberance within a month.

“I don’t think telomere length is the only thing that causes ageing,” says Andrews. “There are a series of ageing processes going on and I think of each one as a stick of dynamite. Telomeres are the stick of dynamite with the shortest fuse. If we find a way of putting that fuse out, we could live to, say, 150.”

Sierra Sciences’ initial attempt at telomeric magic involved painstakingly altering one or two DNA bases out of the thousands that make up the telomerase gene to hone in on the regulatory molecule that acts as the repressor. This would then be neutralised, reactivating the gene. The methodology shifted in 2006 to a strategy of bulk-buying libraries of several hundred thousand chemical compounds and testing each one to see if it would activate telomerase in cultured fibroblasts, which are found in skin and connective tissue.

On the 57,684th run, Andrews’ team found its first telomerase-inducing chemical, though the snappily titled C0057684 was too toxic to be used in a drug. Nevertheless, it was the first discovery that activates the telomerase gene without killing the cells and gave the team positive control.

Then came the economic downturn; two of Sierra Sciences’ investors were forced to bow out and ambition was duly downscaled. Andrews is sanguine about the future, however, with money starting to flow in the shape of a deal with Arizona-based supplement company Isagenix. Launching in August this year, Product B contains several natural compounds that Sierra Sciences has verified to have “telomere-supporting” properties. It is far from the knockout punch in Andrews’ mind, but the first royalty cheque in October was estimated at $250,000 and there are expectations that this will rise substantially over the coming months. Given $40m, he claims he could have a drug ready for clinical trials within three years.

“I strongly believe for every year I spend living this kind of life, I will recoup it many times over,” he says. So, all cards on the table, how long does he really think we can live? “Ask me in 50 years,” he says with no hint of irony. “And then ask me in 100 years. And then ask me 200 years after that – I wouldn’t be surprised, based on what we are doing right now, if people live for 500 years.”

Cynthia Kenyon also has her eyes on the anti-ageing prize, harbouring start-up dreams that stretch far beyond her considerable laboratorial pedigree. To get to the promised land, the Kenyon Lab at the University of California, San Francisco, has pegged a microscopic, distinctly unglamorous roundworm called C. elegans as the “Fountain of Youth, made of molecules and not simply dreams”.

Kenyon is driven by the notion that the ageing process is so much more than a random and haphazard process, and is firmly subject to regulation by genes. “Rats live three years and squirrels can live for 25, and these animals are different because of their genes,” she explains.

Kenyon Lab’s aim is to find the genes that control ageing and alter the activities of the proteins they encode. C. elegans is perfectly configured for this purpose as the worms enter old age and die within about two weeks. To date, Kenyon’s team has discovered that certain genes (daf-2 and daf-16) allow the tissues to respond to hormones that affect lifespan. Through gene manipulation, they have been able to extend the lifespan of active, youthful worms sixfold.

“For centuries people thought you just get old,” says Kenyon. “What has really changed over the past couple of decades is that you can make animals live way longer than their expected lifespan. It is a fundamental difference and something people really didn’t think possible.”

Kenyon’s studies have since been supported by others showing that daf-2-like genes control the lifespan of fruit flies, mice and, potentially, humans.

And, it transpires, longevity is just part of the story. “[Our process turns them] into animals that are very resilient and can resist practically anything you can imagine. For example, they are resistant to high temperature, ultraviolet light, low oxygen – all sorts of nasty things. The animal is on red alert.”

Retaining her focus on C. elegans, Kenyon has identified around 50 genes that affect lifespan and is deep-diving into the science using powerful molecular techniques. As a result, it is now possible to discover if the genes have universal effects on lifespan and can be tested in higher animals. “We’re trying to shift the body from its happy-go-lucky state,” she says. “This is an extremely exciting and important concept that could revolutionise medicine, human health and longevity, and it has just now begun to be studied in earnest. Right now is the time where we have enough of a foothold to move this on to humans.”

Over in London, Aubrey de Grey strikes a similarly optimistic tone. Rangy, long-haired and long-bearded, he cuts a conspicuous figure amid the post-work pub crowd, looking like a mischievous hobo but sounding like an aristocrat. “Ageing is the world’s most important problem,” he says loudly over the noise of an errant coffee-grinder sounding off in the background. “It can be solved.”

De Grey is arguably the most famous, outspoken and, some would say, notorious figure in the field of gerontology, the study of the social, psychological and biological aspects of ageing. He claims that of the 150,000 people who die every day, two-thirds do so from aging. Not only is death from old age unpleasant and undesirable, he argues, it is an expensive societal burden costing more in the final year of life than the rest of the cumulative healthcare combined.

As chief scientific officer of the US-based SENS (Strategies for Engineered Negligible Senescence) Foundation, he presides over an organisational nexus that purports to attract, empower and cheerlead regenerative medicine, specifically the broad category of rejuvenation biotechnologies. It comprises a sprawling network of experts, research projects and affiliated universities and research organisations.

A UK citizen and former computer scientist, de Grey is more about health than the notion of anti-ageing. Longevity is simply a by-product of keeping us all healthy. Famously, he has claimed that the first person to live to 1,000 has already been born. “Regenerative medicine actually turns back the clock,” says de Grey. “What this means is that we can do it repeatedly. In principle, that means we should be able to keep people in a truly youthful state as long as we like.”

According to de Grey there are seven reasons for ageing, all of which basically amount to a hodgepodge of molecular garbage and cellular decay, and he is fomenting solutions to combat pathology for all – a ‘longevity escape velocity’ whereby therapies enable the delay of the ill health from old age faster than time passes, buying breathing space to develop better therapies.

De Grey’s forthright views have a tendency to rub people up the wrong way; in 2006 the Massachusetts Institute of Technology’s Technology Review journal offered $20,000 to any molecular biologist who could demonstrate that de Grey’s SENS theory was “so wrong that it was unworthy of learned debate”. The prize remains unclaimed, as a panel judged that de Grey inhabits a grey area – one that exists in “a middle ground of yet-to-be-tested ideas that some people may find intriguing but which others are free to doubt”.

“We are not part of the anti-ageing industry,” says de Grey emphatically, pointing to his unkempt appearance as evidence he is not in it for the money. “We are not selling anything. We are developing medicines that don’t yet exist.”

At present, the SENS’s strategies are an amorphous mass of potential. But it is a test bed and an increasingly influential catalytic stepping stone. The budget for 2010 stood at $2m and that has been comfortably doubled this year. Ideally, he’d have $100m a year to play with (“a pitifully small amount”), with research centering on mice before being ramped up over time to humans.

“Our reaction over millennia has been to make our peace with ageing. I want to spread the word well enough that everyone wakes up from this pro-ageing trance,” says de Grey. “The only thing you need to know is that ageing is bad for you. Can we cure it? Not yet. But the big thing that has changed over the last decade or so is that now, I believe, we are within striking distance.”

Making a meal of the anti-ageing boom

By Jo Bowman

Twenty years after the first beauty supplement hit the market, the appetite for products that strive to make users attractive from the inside is suddenly growing at an astronomical pace.

The market just for food and drinks that make claims about the effects on appearance is worth an estimated £167.4m (€194m) this year, up from £83.4m (€97m), according to Euromonitor International. Drinks have been the fastest-growing category, with teas and soft drinks, particularly in Asia, becoming huge sellers, and packaged food and dairy products, especially in Eastern Europe, fast movers.

But it’s supplements – tablets and powders – that are really challenging the idea that beauty products are bought in bottles and smeared on, and that a good-skin diet just means cutting down on chocolate and drinking plenty of water. In the US, the trade in internal beauty products (food, drinks and supplements) is expected to rise from $1bn in 2008 to $1.55bn by 2013, in Europe from $1.8bn to 2.7bn, and in Japan from $2.4m to $3bn, according to Datamonitor’s projections.

Some of the biggest – and some of the newest – names in beauty gathered in Paris at the end of October for the second annual Beauty From Within conference, where speakers included representatives from Innéov, a L’Oréal and Nestlé joint venture, and Oeneobiol, which had an annual turnover of €57.2m when it was acquired by pharmaceutical giant Sanofi-Aventis two years ago. The breadth of this booming sector is illustrated in the diversity of delegates: from PepsiCo to Healthspan, PZ Cussons and ingredient suppliers DSM and Gelita.

Upmarket London department store Harvey Nichols now sells Eat Yourself Beautiful collagen marshmallows designed to improve skin tone and reduce wrinkles, Chilean brand Cosmetofood and the oral beauty product Peptan, based on collagen and made by Rousselot. Dove Spa, the Unilever brand, recently launched an anti-wrinkle supplement that’s been five years in development, British ‘hairstylist to the stars’ Nicky Clarke has his own branded tablets to promote healthy, shiny hair, and L’Oréal is even developing a tablet to prevent hair from going grey.

“There’s much more focus now on the concept that you are what you eat,” says Marie-Louise Haxthausen, international marketing director for Imedeen – widely seen as the first beauty pill – which was launched in 1991 by Danish healthcare company Ferrosan. Its tablets promise to improve skin quality and appearance by caring “from the inside, where traditional creams and lotions cannot reach”. The company reports seeing double- digit annual growth almost every year.

The importance of diet on health in Asia means that this is a rapidly growing market for beauty pills, also known as nutraceuticals or nutricosmetics. Amore Pacific, a Korean stable of brands, is expanding apace and has a vision for where it wants to be by 2015: with 10 ‘mega-brands’ in what it calls ‘outer beauty’ (skincare creams and make-up), and five ‘inner beauty’ mega brands accounting for 20% of earnings.

In Latin America, a focus on beauty and youth, and a willingness to try something new, also provide fertile ground for expansion.

Men are another market to be tapped. Imedeen launched a product last year that in most markets is the same recipe as that for women; although in some, it has added vitamin C and zinc to help shaving nicks heal. “Men are spending more on skin and health, and lots of the big beauty brands have been launching men’s lines,” says Haxthausen. “For women, we like our routine of using creams in front of the mirror, but men don’t get that same pleasure from it. They just want an easy way to solve their dry skin problem or their shaving rash, and being able to just take a couple of tablets a day is quite appealing to them.”

Mintel research shows that while the European market for shaving products is pretty stagnant, sales of men’s skincare products rose 45% in the five years to 2010, from €289m to €420m. In Spain alone, the sector grew 76%. Men show a huge interest in looking young, which has fuelled demand for skincare products that combat signs of fatigue, stress and ageing. “An increase in information about male grooming in the media, the availability of a wider range of products, and the wider usage of celebrities to endorse brands has benefited the male grooming category,” says Mintel global skincare analyst Nica Lewis.

Indeed, one of the best-known American supplement companies, BORBA, was launched by and is fronted by a man. Scott-Vincent Borba, who had worked in product development and marketing with the likes of Shiseido, Neutrogena and Wella, founded it in 2004, having struggled to find skincare products to suit his own problem skin. The company’s mantra is “Where inner health meets outer beauty”, and it sells a vast range of creams, edible liquids, chews and water-based drinks that set out to tackle signs of ageing, aid weight control and improve energy levels. “At BORBA, we believe that good health and beauty are one in the same, so we partner luxurious, eff ective topical skincare products with vitamin and antioxidant-packed supplements that work synergistically to heal your body and perfect your skin,” the company says.

While consumer demand for antidotes to the signs of ageing, dull hair and orange-peel thighs is hardly in short supply, disparities in regulation make international expansion something of a headache. Regulators disagree about whether nutricosmetics or nutraceuticals should be classed as food, cosmetics or pharmaceuticals, and what rules should apply to how they’re sold.

In the UK, one supplements company was reportedly told it had crossed the line into the world of medicines by using the word ‘spot’ to talk about a skin imperfection; using ‘blemish’ instead put it back into the food category.

The US Food and Drug Administration says a product can either be a cosmetic, a drug or both – in which case it must comply with two sets of regulations. Which one it counts as depends on the claims made in its packaging and promotional material; whether it contains ingredients considered to be drugs because they have a well-known therapeutic use; and consumer expectations of what the product will do for them.

The European Food Safety Authority, EFSA, is considered to have some of the most restrictive rules on what can be claimed by oral beauty products. Those in Japan are also strict, with the result being that many beauty products don’t make specific claims about what they do, but rather talk up the active ingredients they contain, which have a reputation for achieving certain results. In the UK, the Advertising Standards Authority is setting up a panel of experts to help rule on contentious claims in ads. This year it banned several heavily airbrushed ads by L’Oréal brands Lancôme and Maybelline for being unable to prove the pictures represented the results that could be achieved.

There are blurred lines within the sector, too, with food producers and cosmetics makers all involved in the development of ‘beauty from within’ products. Indeed, Ferrosan has recently been acquired by Pfizer, the drugs manufacturer best known for Viagra. And university researchers in North Carolina are in talks with cosmetics producers to use anthocyanins – the pigments that give berries their deep purple colour – in commercial applications. Their richness in antioxidants is thought to inhibit the effects of the ageing process, and is also attracting interest from cancer researchers.

“It’s both a challenge and an advantage in many ways,” says Haxthausen. “It’s always been important for us to document what we claim is what the product does, and this is especially important when people are consuming a product versus using a topical product. We think regulation is a good thing, because then you avoid companies overclaiming what they can do, which discredits the whole industry, but in some countries you find very tough regulations and others not. More consistency would help.”

Mark Whalley, a senior analyst at Datamonitor’s Consumer Business Unit, says the “regulatory roulette” governing nutraceuticals fuels consumer scepticism over whether beauty pills really make any difference to appearance and is probably holding back the industry.

“The problem for consumers is that it’s difficult to measure the results of the products,” he says. “If you’re the type of consumer who’s interested in these types of products, you probably already have quite a substantial beauty regime, so how do you attribute what’s happening to the food or drink or tablet in particular?”

Of course, for many of those who see results with a combination of products, it probably doesn’t matter which element in the daily regimen is making the difference, as long as something is. And for others, desperation will drive them to keep trying new products.

Whalley says: “We will see high growth in this area... but I don’t think it’s ever going to be a truly mainstream practice in the same way that having an Actimel [probiotic drink] in the morning has become mainstream.”