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A longevity diet that hacks cell ageing could add years to your life
A new diet based on research into the body's ageing process suggests you can increase your life expectancy by up to 20 years by changing what, when and how much you eat
HEALTH 28 June 2022 By Graham Lawton
I HAVE seen my future and it is full of beans, both literally and metaphorically. As well as upping my bean count, there will be a lot of vegetables, no meat, long periods of hunger and hardly any alcohol. But in return for this dietary discipline, my future will also be significantly longer and sprightlier. I am 52 and, on my current diet, can expect to live another 29 years. But if I change now, I could gain an extra decade and live in good health into my 90s.
This “longevity diet” isn’t just the latest fad, it is the product of more than a human lifespan of scientific research. And it isn’t merely designed to prevent illness, but to actually slow down the ageing process – that’s the claim, anyway.
Of course, it is a no-brainer to say that our diets can alter our lifespans. Worldwide, millions of people still die prematurely every year from lack of calories and nutrients. Meanwhile, an estimated 11 million die each year from too many calories and the wrong sort of nutrients. Scoffing more than we need inevitably leads to obesity and its pall-bearers, cardiovascular disease, diabetes and cancer. Typical Western diets are also high in sugars, refined starches and saturated fats and low in wholefoods, which add insult to injury by disrupting metabolism. That includes the excessive release of insulin, the hormone that keeps blood sugar levels under control and has a direct impact on ageing. Suffice to say that Western diets don’t push the longevity lever in the right direction. But is it really possible to eat oneself into a later grave?
In the US, between 1970 and 2009, average daily calorie intake rose by 20 per cent, to 2520 kilocalories. Other Western countries have followed that trend. The shocking extent to which our obesogenic, disease-promoting and pro-ageing diets are shortening our lives was revealed in recent work from the University of Bergen in Norway. Researchers led by Lars Fadnes modelled what would happen to people who switched from a typical Western diet to their optimal one containing more wholegrains, fruits, vegetables, nuts, legumes and fish and less meat, dairy, refined grains and sugary drinks. Based on data from a huge research project called the Global Burden of Disease study, which, among other things, analysed diets and diet-related illnesses across 195 countries, they found that Westerners could typically buy themselves a lot more time.
Switching to this optimal diet at age 20 and sticking to it would extend average life expectancy by more than 10 years for women and 13 years for men. And it is never too late: 60-year-olds shifting to this diet would gain eight years of life expectancy and 80-year-olds an extra 3.4 years. Even a diet that is a halfway house between a typical Western one and the team’s optimal one would add six to seven years if adopted at age 20. These surprisingly large responses are probably because the diet immediately improves metabolic health, says Fadnes. “We haven’t gone into the mechanisms, but our hypothesis is that the longevity expectations are linked to reduction in cardiovascular disease and, to some degree, reduction in the risk of cancer,” he says.
In other words, a healthy diet can prevent diseases linked to a bad diet. Who knew? However, for decades, many researchers have believed we can do even better, by hacking our biology to actually slow the ageing process.
The first inklings came over a century ago. In 1917, researchers at the Connecticut Agricultural Experiment Station in New Haven discovered that female rats that had been starved as pups subsequently stayed fertile longer than average and lived to a ripe old age. Further experiments confirmed that this “caloric restriction without malnutrition” – achieved by cutting calories by up to 60 per cent while supplementing the diet with vitamins and minerals – kept mice and rats healthy and alive for longer. The earlier it was started and the more stringently it was applied, the greater the gain.
Caloric restriction has since been shown to be capable of extending healthspan and lifespan in every organism it has been foisted on, including yeast, flies, worms and primates. The results vary widely, but some of the gains in lifespan are spectacular. Mice on caloric restriction, for example, can live up to 50 per cent longer than average – which would translate to about 120 years if replicated in humans.
But can it be replicated in humans? Unfortunately, doing human caloric-restriction experiments is extremely difficult. Not only do people find it very hard to halve their energy intake for more than a few days at a time, but the experiment would also have to run for many years to assess whether it had any life-extending effect. “In people, we don’t even really know that caloric restriction has long-term significant health benefit,” says Matt Kaeberlein at the University of Washington in Seattle. And we do know that it can seriously damage the health of people who limit their caloric intake as a result of eating disorders. It is important to note that no one should restrict their diet to the extent that it damages their health.
Nevertheless, there are reasons to believe that caloric restriction would extend lifespan in people. One is basic biology. It turns out that, regardless of species, the mechanism by which caloric restriction exerts its life-extending effects is essentially the same: a network of metabolic pathways that assess the availability of nutrients and respond by toggling cells between two biological states, feast and famine. When nutrients are plentiful, these pathways stimulate cells to grow and divide. When they are scarce, cells are told to hunker down and await better days. “We see most organisms going into a maintenance mode and not ageing very much,” says Valter Longo at the University of Southern California in Los Angeles.
Crucially, part of that process is to sweep up intracellular debris, such as damaged molecules and organelles, to burn as fuel, a bit like throwing bits of broken furniture onto the fire. This detritus is a direct cause of the cellular damage that results in ageing, so destroying it – a process called autophagy – prevents such damage from occurring. Starvation also boosts repair processes, which can reverse damage that has already been done.
Feast or famine
One key player in this nutrient-sensing system is the insulin receptor. When insulin is released in response to a spike in blood glucose, this cell-membrane protein switches on and helps turn the system to growth and reproduction. It does this in part by activating another nutrient sensor called mTOR, which is the linchpin of the feast-famine system and is of intense interest in anti-ageing circles. When mTOR is on, autophagy and repair switch off. So if glucose is constantly flooding into the bloodstream, the insulin receptor gets stuck in the “on” position and mTOR is chronically activated.
Animals subjected to caloric restriction show increased sensitivity to insulin, along with improved liver function and loss of weight and body fat. All these biological indicators were also seen during a rare human trial called CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) in which people consumed 25 per cent fewer calories for up to two years. This is another reason for optimism about human caloric restriction, but it still doesn’t get around the fact that the regime is very hard to stick with.
However, there is some evidence that less-onerous diets have similar effects – at least in mice. Many involve restricting calories some of the time, such as periodic fasting, which entails eating next to nothing for two days each week, or every other day, or for up to four consecutive days a month. Another is time-restricted eating, such as the 16:8 diet, when all the day’s calories are consumed in an 8-hour window bookended by 16-hour fasts. Both these types of diet are sometimes called intermittent fasting. A third approach is the fasting-mimicking diet in which, for a period of five days a month, individuals eat a plant-based meal plan low in sugar, carbs and calories but high in fat that is designed to evoke the fasting response without total abstinence. (Longo holds patents related to fasting-mimicking diets and has equity in a company that sells them.)
If we can tap into the body’s anti-ageing pathways, we can increase healthspan as well as lifespan
Other diets that promote longevity in rodents don’t even require fasting, but these are more complicated to follow. Protein restriction, for example, is based on reducing the calories obtained from protein from the normal 10 to 15 per cent to around 5 per cent, with the calories replaced by carbohydrates. More elaborate still is amino-acid restriction, which limits consumption of some of the building blocks of proteins. The main target is ethionine, found mostly in animal proteins, with cuts of 80 per cent or more required. Another is tryptophan – sources include milk, chicken and oily fish – which must be reduced by about 40 per cent. Cutting branched-chain amino acids such as leucine, isoleucine, and valine – mostly found in meat, dairy and cereal – by two-thirds also works. These restrictions appear to exert their effect through mTOR, though exactly why the body responds in that way isn’t clear.
Such interventions are generally less effective than full-on caloric restriction. Protein restriction, for example, extends mouse lifespans by about 15 per cent compared with 50 per cent, while time-restricted feeding gives about a 10 per cent boost. But the fact that they are easier has led to claims that they can be directly applied to humans. The past few years has seen a torrent of questionable anti-ageing diets based on this research, says Kaeberlein. “When people start recommending these dietary interventions to the general public, they’re doing so in the absence of any real data suggesting that it’s beneficial, beyond the benefits you get from not being overweight.”
Now, however, such claims are finding their way into the scientific literature. In April, the prestigious journal Cell published a review paper containing a “longevity diet… to optimize lifespan and healthspan in humans”. The authors – Longo and Rozalyn Anderson at the University of Wisconsin-Madison – blended decades of research on the biology of ageing, the effects of caloric restriction and similar dietary interventions, and knowledge on the health benefits of various food groups, including from the recent University of Bergen study. Then, they seasoned it with data on the dietary habits of people living in longevity hotspots such as Okinawa in Japan and Sardinia in Italy. The end product is a diet that could add years to a typical person’s life. “It’s going to be associated with a huge effect,” says Longo. “You’re starting to get into 15 to 20-year changes in life expectancy.”
The main ingredients of this longevity diet – which is yet to be tested in trials – are enough caloric restriction to stay slim, a daily regime of very mild, time-restricted feeding, a few five-day cycles of fasting-mimicking each year and a largely plant-based diet (see “The longevity diet“). This, says Longo, delivers both a conventional healthy diet that guards against obesity and its consequences, and also taps into the longevity-enhancing starvation response. “This is what we know works, based on epidemiology, clinical trials, basic research and centenarian studies,” he says.
Hold on a minute, says Kaeberlein: even in mice, the evidence for the benefits of time-restricted feeding is slender. “There have been a few studies, but they’re almost all short-term – usually eight to 12 weeks – where people claim to see benefits in some cases, and in other cases no benefits. I’d say the body of work is unconvincing.” And it is a similar story with the fasting-mimicking diet. This is essentially a period of caloric restriction and, despite a widespread view that such restriction invariably works, that is a myth. Only about half the strains of lab mouse it has been tried on have the “correct” response, some don’t respond at all and about a third live shorter, not longer, lives. “We don’t really understand why that is,” says Kaeberlein, “It’s a little bit risky to start recommending these things to the general public when even in mice, a third of the time, it actually reduces lifespan and increases mortality.” On top of that, most people who attempt caloric restriction also experience unpleasant side effects, including disturbed thermoregulation, loss of libido and increased susceptibility to infection.
Longo is dismissive of these warnings. “The idea is to keep it very, very safe,” he says. He could have recommended something much more hardcore, with caloric restriction, 16 hours of daily fasting and a monthly bout of the fasting-mimicking diet, but deemed it too risky. “Could it help? Yes. But could it hurt? Yes, it could too. So we don’t go there.”
The proof of the pudding, of course, will be in the eating. Longo has just secured funding to do an 18-month clinical trial in Italy. He will recruit 500 people and put half of them on the longevity diet, leaving the rest on their normal chow, then track biomarkers of improved health and longevity. He doesn’t have any doubts it will be safe and effective. In fact, he follows the diet himself and has done for 30 years. But while we wait for those results, it is never too late to start living, so pass the beans.
Always consult your doctor before radically changing your diet
The longevity diet
Research published in April identifies six steps designed to increase lifespan by promoting lean body mass and healthy blood sugar levels, switching off the body’s central pro-ageing system and ramping up an anti-ageing process called autophagy:
1 Limit calorie intake to maintain a body mass index of 22 to 23 for men and 21 to 22 for women.
2 Eat a diet high in wholegrains, legumes and nuts. Stop eating meat to restrict intake of the amino acid methionine, but include some fish.
3 Aim to get between 45 and 60 per cent of calories from non-refined complex carbohydrates, 10 to 15 per cent from plant-based proteins and 25 to 35 per cent from plant-based fats.
4 Do a limited daily fast, eating no calories from around 3 hours before bedtime and for the next 11 to 12 hours.
5 Every two to three months, undertake five days of a fasting-mimicking diet (see main story).
6 Alcohol is allowed in small amounts, but no more than 5 units a week.
Article amended on 29 June 2022
We have corrected step 5 of the longevity diet.