Society is currently in the middle of a technological revolution. One day, we may reach a point where medical technology could add years to our life expectancy faster than we can live them. This is called the “Break-Even Point” and some scientists think that it’s only a matter of decades before we achieve it. Unfortunately, many of us do not have the option of waiting that long. But there is a way to slow down our biological clocks so that we can live that long.
With enough effort, you could be able to buy yourself enough time to be among those who reach the “Break-Even Point“. You can take all the geroprotectants and nutraceuticals you want, but there is only one solid scientifically proven, reliable way of extending one’s lifespan. It’s called the Caloric Restriction Diet, or CR for short.
One day, humans will be able to replace damaged organs like car parts and, after a serious accident, will be able to fix their damaged bodies at a human body shop with lab-grown replacement parts. But this is still relatively far in the future. Fortunately another approach to make a car last longer is to simply reduce mileage and drive it less. This same logic also applies to humans.
Caloric Restriction is a diet where you cut your daily calorie intake by about 30% to 50% in an effort to increase your maximum lifespan. You can also practice it by eating healthy nutrient-dense foods to avoid malnutrition. That form of the diet is called CRON, which stands for “Calorie Restriction with Optimal Nutrition.” The people who take on this new lifestyle are referred to as CRONies. Whether CRON works is debatable. Some CRONies report becoming miserable with low sex drive and high irritability. Meanwhile, other CRONies who say they’ve been doing it for years have never felt better. Either way, it’s a big commitment. So how do we know that it works?
To begin with, caloric restriction has been shown to significantly extend lifespan in a number of species including yeast, nematode worms, fish, rodents and dogs, just as long as the diet wasn’t done to the point of malnutrition. It’s been proven that what some call semi-starvation, slows down the biological aging process and extends youth, health and maximum life expectancy. The effect on lifespan is very dramatic. Rats who are fed a shockingly low number of calories live up to 40% longer than rats who were fed normally.
In the 1980s, professor Roy Walford at the University of California, Los Angeles produced the world record for the longest living mouse at the time. Most mice barely lived over two years. But Dr. Walford managed to produce one that lived to 49 months. The exact mechanism is not known, but some scientists think that fasting turns on survival genes that fight stress. Other scientists think that the lack of glucose from eating less lowers the amount of free radicals in our cells. Radicals are molecules that damage our mitochondrial DNA through the double strand break problem. Damage to this mitochondrial DNA stops the cells from doing their jobs and causes aging. Therefore, running the mitochondria on fewer calories will produce less free radicals and consequently, slow down aging.
But there’s a catch. The biggest problem with caloric restriction is that it hasn’t been tested in humans, mainly because those tests would take many decades. It’s easier to study dogs which have considerably shorter lifespans. Despite this setback, it’s still very likely that the metabolic mechanism of caloric restriction is fundamentally beneficial to all mammals. So whichever mammal we study shouldn’t matter that much, even if there are varying degrees of success. As such, the diet might not give humans the same amount of extra life that Dr. Walford’s mice got, but it’s definitely better than no extra life at all.
Since we couldn’t test caloric restriction on humans, the next best thing was to test it on our genetically closest relatives through a famous study called the “Madison Monkey Experiment.” In the city of Madison, Wisconsin, researchers are spending millions of dollars to see if caloric restriction has the same effect in primates as it does in mice. So they’ve taken two groups of rhesus monkeys and locked them up for life. One group of monkeys was given a regular diet while the other group of monkeys was only given 70% the amount of calories that the first group got. Rhesus monkeys are one of our closest evolutionary relatives, but they only live for 25 years, which makes them easier to study than humans.
Many decades after the study began, it was finally finished and published in 2017. A collaborative report by scientists of the US National Institute on Aging and the University of Wisconsin showed that caloric restriction did in fact delay the effects of aging. The CRONies that were studied in the Madison Monkey Experiment showed lower body weight, lower fat mass, lower blood glucose and fewer disorders of Aging. Since these rhesus monkeys are so genetically similar to humans, the benefits are very likely to apply to humans as well, which has now resulted in millions of people around the world practicing caloric restriction, a new generation of CRONies.
So we know that the less you eat, the longer you live. Just don’t actually starve yourself. The key is to phase in the diet slowly enough that you don’t lose weight too quickly, because it could affect your health. And if you phase in the diet too quickly, then you might also relapse and start overeating again. The overall goal is to eventually get from 2,000 calories per day down to around 1,400 calories, depending on your age and height.
But is the CR diet dangerous? Well, not really. Society has changed a lot in recent decades. We no longer live very active lifestyles so we don’t need to eat as much as our parents did. Obesity has become so prevalent that more people in the world are dying from overeating than from starvation. Because of technology and our sedentary lifestyles, our bodies don’t need the same energy that our ancestors did. Large breakfasts, as seen in TV cereal commercials, contain far too much food, especially if you live a sedentary lifestyle, which is the case for most Americans. We need to start eating less food because our habits are literally killing us.
Many CRONies who try the CR diet report being hungry initially, but then started feeling much better once they got accustomed to eating less food. A good way to ward off the initial hunger is to eat lots of fiber which will make your body feel full. Although fiber rich foods have very few calories, people who do the CR diet improperly, without fiber or vegetables, tend to become angry, emotionally distant, hungry, and have a very low libido, in which case they are probably undoing the positive effects of caloric restriction by adding stress and depression, which are associated with rapid aging. So be careful, because if you jump right into the CR diet without gradually easing in first, you might cause your body to create higher levels of a stress hormone called cortisol, which would counteract some of the good that the diet would otherwise produce. So without fiber, it will not be an easy diet to keep. Regardless, CRONies still believe that there’s a good chance that technology will become available to dramatically extend their lives if only they can live long enough.
You might find it annoying to eat smaller meals, but it’s more important to put your health first so that you can live long enough to benefit from radical life extension technology. But the CR diet is not for everyone. It can be really tricky to eat just enough to sustain your body, but also get enough nutrients to be in peak health. Caloric restriction means you will have to shop healthy, but unfortunately, not everyone has access to quality stores, so it would be great if we had a way of getting the benefits of the CR diet without actually having to monitor what we eat.
We could potentially get the benefits of caloric restriction in three ways. They are:
- By supplementing hormones
- By taking drugs to manipulate gene expression, and
- By customizing our genomes altogether.
First there’s the idea of hormone supplementation at the chemical level. Much of modern caloric restriction research is focused on the role of a hormone called Dehydroepiandrosterone or DHEA for short. DHEA is the most abundant steroid hormone in the human body and it works as an inhibitor of the stress hormone cortisol. DHEA also helps rejuvenate female fertility. But the fact is that our levels of DHEA plummet as we age, so that cortisol will eventually kill us.
Interestingly, when studying the DHEA levels in the older people of the Japanese island Okinawa, it was found that their bodies still had high levels of the hormone. This is because the people of Okinawa practice “Hara Hachi Bu,” which is a form of caloric restriction. This is probably why Okinawans are the longest living population in the world and why Okinawa is considered a so-called “Longevity Blue Zone.”
Perhaps the rest of us could be just like the Okinawans if we could only find a way to up-regulate our DHEA levels. It’s no surprise that DHEA is now being touted as the Fountain of Youth and sold as an over-the-counter supplement. But, as with all nutraceuticals, there are always concerns about safety, side effects and lack of quality control, not to mention the supplement industry is often riddled with frauds. Supplements are not regulated or approved by the FDA, so supplement companies can mislead you about the ingredients. Many supplements will just outright lie on the bottle and not have DHEA inside them. There’s also the question of whether or not the supplement is even biochemically equivalent to the natural form of DHEA.
As such, the second way to get the effects of caloric restriction may come from epigenetics. For example, many people died during the Irish potato famine of the 1840s, but in the long-term, average life expectancy for that generation went up from 40 to 50. It’s hard to believe that an entire decade of extra life can come from just missing a few meals every week, but this is because hunger is the natural state of human beings. Evolution designed our bodies to last days without eating. We are not meant to gorge ourselves into obesity because we are, genetically, hunter-gatherers at heart and hunter-gatherers don’t expect to eat very often. This is probably why calorie restriction raised the life expectancy of the Irish potato famine generation.
Scientists think that these molecular effects are linked to a gene called LOS1. We have reason to believe that the amount you eat can now switch the gene on or off, making you age either slower or faster. It also affects a group of genes called the Sirtuins, which were the life’s work of MIT aging biologist Leonard Guarente. If he sounds familiar, it’s because Leonard Guarente created a popular anti-aging drug called “Basis.” Dr. Guarente was the first to discover that he could get the anti-aging effects of caloric restriction when he made yeast cells express the sirtuin genes more often. When he promoted expression of the most powerful gene called SIRT2, the yeast lived 50% longer. He also realized that decreasing the expression of the gene would make the yeast die sooner, even if put on a caloric restriction diet, which means caloric restriction does not work without the LOS1 gene.
It turns out that the sirtuin genes are stress regulators, thus explaining why lower cortisol is linked to longevity. They are also linked to the hormone, DHEA. Dr. Guarente was able to activate these sirtuin genes using semi-starvation, which kicks the sirtuins into overdrive, boosting DNA repair and stopping the cells from dying. Just like yeast, humans possess sirtuin genes as well. So perhaps we could find a way to activate those genes without having to cut calories.
Dr. David Sinclair, who is a postdoc in Guarente’s lab, thinks that taking a molecule called a Resveratrol could be the key to expressing the sirtuin genes. Resveratrol is the molecule in red wine that gives it all the health benefits we keep hearing about. When resveratrol is given to mice, worms and flies, it helps them live 25% to 40% longer. For that reason, Dr. Sinclair has spent his entire life trying to get resveratrol turned into a nutraceutical, so that we can mimic the effects of caloric restriction in humans. However, we might not have to take resveratrol at all, because perhaps we could just genetically engineer ourselves to get rid of all the risk genes for aging.
The third method to mirror the effects of caloric restriction might involve redesigning our genomes altogether and knocking out all the genes that make us age. Molecular biologist Dr. Cynthia Kenyon from the University of California, San Francisco, has been able to radically extend the lifespan of microscopic worms called C-elegans. All she did was simply delete one gene called DAF2 and the animals lived twice as long. DAF2 is a gene that increases the effects of insulin, but when Kenyon mutated the gene, it had the same effect as caloric restriction. This is because decreasing your food intake also leads to a lower level of insulin. So these genes could be organized to promote life extension. The lack of insulin might also help promote survival genes like the sirtuins. So this method might be better than the last two. When the equivalent genes for DAF2 were adjusted in mice, the drop in insulin levels had the same positive effects, also making them more resistant to heart disease and cancer.
This is a groundbreaking new way to treat diseases and target aging at its genetic source. Unfortunately, it’ll be awhile before we can make gene editing technology safe enough for humans. In the meantime, Dr. Kenyon is working with the famous aging biologist Elizabeth Blackburn on another project to naturally boost our DHEA levels. A study done a while back actually shows a 20% increase in DHEA levels after just 5 days on a lacto-vegetarian diet. The large fibre intake of vegetarians is associated with higher levels of DHEA . This is not because they were taking supplements or taking more of the hormone in, but because they were losing less of it. To figure out why, Kenyon and Blackbird got involved in the CRONA Study at the University of San Francisco, where hopefully, they will figure out a way to stall the aging process, at least until gene editing technology is perfected.
In conclusion, it’ll be a long time before we can get the benefits of caloric restriction without doing the nutritional work it requires. One day we might produce a drug that will elicit the benefits of stress regulating genes without having to do the diet, but until then you’re just going to have to eat healthy. You don’t have to join the CRONies, since a plant-based diet might have many of the same effects as the CR diet. After all, taking resveratrol and doing caloric restriction are still somewhat controversial in the scientific community. But the big takeaway from this is that you should just live more sensibly. Stop eating so much, consume more fiber and maybe incorporate a few more plants into your diet.