What Gets Measured Gets Managed
We can survive injuries to many organs. Lose a kidney? Fine. Lose half your liver? Fine. Lose a limb? Fine. But two organs stand out as vitally important: the heart and the brain. If something bad happens to either of them, we’re in deep trouble. This is visible on the list of our biggest killers. In most countries, the number one killer is cardiovascular diseases – most notably heart attacks and stroke.
Unfortunately, researchers in this field suffer from a condition that requires them to make every term as convoluted and hard to spell as possible. We want to stay healthy in old age, though, so let’s give it a shot anyway.
Most cardiovascular diseases are due to something called atherosclerosis. Which is a subtype of arteriosclerosis, not to be confused with arteriolosclerosis. Yes, I know.
You can think of atherosclerosis as fatty plaque building up in the walls of your arteries, like the pipes beneath a sink slowly getting clogged. Over time (and due to the decline of ageing), this build-up can eventually cause trouble. An artery can get blocked, or a piece of fatty debris can dislodge, travel through the bloodstream and block a smaller blood vessel. In both cases the result is that downstream tissue doesn’t get enough oxygen, and becomes damaged or dies. Again, this is especially bad if that tissue is in the heart (heart attack) or the brain (stroke).
We can age without much atherosclerosis, but ageing is a huge risk factor. Young people just don’t get heart attacks. However, the initial signs of atherosclerosis can show up early in life. For instance, during the Korean War, American doctors were surprised to find that almost eighty per cent of deceased soldiers had signs of fatty plaque in the blood vessels supplying the heart. These men had an average age of twenty-two. It turns out that even children can have blood vessels with (very) early signs of plaque development – especially if they live with smokers.
In some genetic conditions, the process of atherosclerosis is vastly accelerated. One of them, ‘familial hypercholesterolaemia’, was named to keep non-native English speakers like me awake at night. We can call it ‘FH’ from now on. If left untreated, people with FH have five to twenty times the normal risk of heart attacks and stroke. Half of men with untreated FH get heart attacks before turning fifty, while a third of untreated women get them before sixty. It seems whatever is happening in FH, we should seek to do the opposite.
The mutations causing FH make the liver worse at removing something called LDL cholesterol from the blood. LDL is technically a protein that transports fats around the body, but you can simply think of LDL cholesterol as ‘bad cholesterol’. People with FH have much higher levels of LDL cholesterol in the blood than normal because their bodies don’t remove it sufficiently. Sometimes they have so much that they develop visible yellow deposits above the eyes. Cholesterol is also a part of the fatty plaque that builds up inside arteries, so at this point we have a smoking gun.
We also know people with the opposite disposition from FH. Certain mutations in the gene PCSK9 make the liver aggressively remove LDL cholesterol from the blood, ensuring abnormally low levels. This condition vastly decreases the risk of heart attacks.
The case strengthens as we see the same pattern in regular people: the higher your blood LDL cholesterol levels throughout life, the higher your risk of getting heart attacks and strokes. Even within normal ranges. Lowering LDL cholesterol levels using drugs or lifestyle changes decreases the risk, and the drop is proportional to the drop in LDL cholesterol levels. Again, even within normal ranges.
Despite the overwhelming amount of evidence, some people desperately want cardiovascular diseases to be about something other than cholesterol. They have even tried constructing elaborate conspiracy theories where cholesterol is harmless and Big Bad Pharma is just out to steal our money. One reason that theory is tempting to some is that eggs are delicious, but also have a high cholesterol content. Health authorities used to vilify eggs based on the logic that eating a lot of cholesterol would increase blood levels of LDL cholesterol, causing heart attacks. However, health authorities have relaxed a bit lately. If you like eggs, you can take a deep breath, too. You see, we don’t just get cholesterol from our food; our bodies can make it by themselves as well. In fact, most of the cholesterol in our bodies is not from food we’ve eaten, but instead has been produced by us. That means there isn’t necessarily a connection between how much cholesterol you eat and how much cholesterol you have in your blood. If you eat more cholesterol, your body will simply turn its own production down.
There’s some pretty intense examples of this. In one case study, doctors discovered an eighty-eight-year-old man with dementia who was eating twenty-five soft-boiled eggs a day. He had kept this habit up for years, but despite ingesting humongous amounts of cholesterol (and being old), his blood LDL cholesterol was perfectly normal. Doctors would never have suspected this man of being a real-life incarnation of the Easter Bunny if carers hadn’t told them about his egg habit.
The man’s secret was that his body had adapted to the unusual diet. Doctors found that he only absorbed a little of the cholesterol he ate, that he had increased cholesterol loss and that he produced little cholesterol on his own. All of this was his body’s way to keep cholesterol levels in check while living on nothing but eggs.
There are similar results from studies in the 1970s and 1980s, where doctors experimented with using a diet of thirty-five eggs a day to treat patients with severe burns. Again, the patients had normal blood values for cholesterol throughout the studies, despite their gargantuan cholesterol intake.
I’m not going to recommend you try these diets, but eggs are delicious and also perfectly healthy. Research on more reasonable diets suggests that moderate egg consumption (one a day on average) does not increase the risk of atherosclerosis at all.
That doesn’t mean we cannot influence LDL cholesterol levels using our diets, though. You might have noticed that I haven’t included a ton of advice in this book in the form of ‘eat this specific herb/mushroom/plant and live forever’. This is mostly because such claims are almost always false. But I’m going to make an exception here. There’s actually some pretty good evidence that eating garlic (both as actual garlic and as supplements) incurs several health benefits, among them lowering LDL cholesterol levels in the blood. Researchers report the following side effects: ‘Garlic odour, breath or taste was noticed in a greater proportion of participants in the active treatment group.’ But despite that, I’m sure eating more garlic is a habit you can get behind.
An even better dietary trick for lowering LDL cholesterol is eating more dietary fibre. You see, we used to eat a lot more fibre than we do today. Both hunter-gatherers and medieval peasants had to actually chew their food, and one of the reasons is that they ate more foods with a high fibre content. Modern hunter-gatherers who still live like this have significantly lower LDL cholesterol levels than us, and also substantially lower risks of cardiovascular diseases.
Similarly, in modern societies, high intakes of dietary fibre are associated with living a long life. Is that just a longevity cargo cult, i.e. because rich, educated people eat more fibre?
No. Randomised controlled trials prove that dietary fibre intake lowers LDL cholesterol levels. When people add extra dietary fibre to their diets, their LDL cholesterol levels reliably fall. The mechanism is well understood, too. We can’t digest dietary fibre, which means it passes through the digestive system intact. On the way, it traps something called bile acids, which we use to digest and absorb fat. Our bodies try to recycle bile acids by reabsorbing them after use, but when they get trapped by fibre, we lose them. That means the liver has to make new bile acids – and the starting material for that is cholesterol, which is recruited from the blood. This mechanism might explain why modern people tend to get high LDL cholesterol levels in the first place. By evolving on high-fibre diets, our bodies expect us to lose considerably more bile acids than we do now, and are ready to compensate with LDL cholesterol in the blood. Remove the fibre, and suddenly LDL cholesterol levels get too high.
You can get more dietary fibre in two ways. The simplest solution is to include more fibre-rich foods in your diet. Fibres from oats (for instance, in the form of oatmeal in the morning) have been particularly well-studied, but really, any fibre-rich food will do. Wholegrains, beans and fruits such as apples and pears are all excellent sources of dietary fibre. The other option is to use fibre supplements. Obviously, whole foods are preferable, but none of us is perfect. The most popular and well-documented approach is to take supplements containing psyllium. Studies usually use 5–15g a day, taken in 5g doses with one, two or three meals. (Obviously, cholesterol-lowering drugs are also an option if LDL cholesterol levels cannot be adequately controlled by diet or lifestyle.)
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Another major risk factor for cardiovascular diseases is hypertension, or high blood pressure. The vast majority of people who have a heart attack or stroke have high blood pressure beforehand.
One of the important hormones involved in controlling blood pressure is called angiotensin II. When this hormone binds to its corresponding receptor, blood vessels constrict, raising blood pressure. You can think of it as squeezing on a water hose. If the same amount of water has to pass through, it will do so under higher pressure. Interestingly, there’s a genetic variant in the receptor for angiotensin II that is overrepresented among centenarians. This means it might increase the likelihood of living a long life. The mechanism is straightforward: this genetic variant makes it harder for angiotensin II to activate the receptor, meaning it protects against high blood pressure.
Researchers in Italy have created mice with an extreme version of this trait by completely deactivating the angiotensin II receptor. These mice are genetically immune to high blood pressure and reap the benefits by living twenty-six per cent longer than usual. This is interesting, because you don’t have to be a genetic mutant – we already have drugs that can do the same thing. When rats are treated with one of these drugs, they, too, live longer than normal. This stuff supposedly works even in the laboratory worm C. elegans, which is quite remarkable considering it doesn’t even have blood vessels.
Clearly, it’s a good idea to avoid high blood pressure if you want to live a long and healthy life. Unfortunately, however, blood pressure tends to increase with age. Some people say this is inevitable, but is it really?
Unknowingly, the Venezuelan government has set up a unique experiment to help us answer that question. In the Venezuelan part of the Amazon, on the border with Brazil, there are several tribes living a traditional hunter-gatherer lifestyle. That is, they hunt to get meat, gather various edible plants and have a low-tech way of life. Tribal members get plenty of exercise, but their lifestyle also provides time for relaxation and lots of social interaction.
The Venezuelan government has built a runway on the territory of one of these tribes, the Ye’kuana. In response, the tribespeople have begun trading their way to tasty processed foods when visitors arrive by air. Other tribes, such as the related Yanomami, however, still live in complete isolation on their ancestral diets.
American scientists have gone to Venezuela to study how this disparity has affected the health of the tribespeople. They found that blood pressure tends to rise with age among the
runway-having Ye’kuana people, just like it does in the developed world among the rest of us. But among the isolated Yanomami, there is no age-related increase in blood pressure. When living on their ancestral diet, these people seem to age without ever getting hypertension. Scientists have found something similar among the indigenous Tsimané people of Bolivia. Here, too, blood pressure rises with age, but only when groups have access to processed food.
This suggests increasing blood pressure isn’t necessarily part of getting old; it’s not a ‘natural’ part of ageing. In fact, it might be completely avoidable. All you have to do is move to the jungle and catch your food with a spear.
Failing that, I have some advice for you that might be a little easier to implement. For instance, we’ve already learned about one thing that tends to increase blood pressure: cytomegalovirus (CMV) infection. It is not unlikely that other chronic viral infections do the same so vaccinations and hygiene is relevant once again.
In a pleasant surprise, it also turns out that most things you can do to lower LDL cholesterol levels work equally well for high blood pressure: eating more dietary fibre, losing weight, quitting smoking and, yes, also eating garlic.
However, there is also an additional drug that works particularly well for lowering blood pressure. Not only that, it also lowers blood sugar, increases autophagy and improves mitochondrial function.
In 1991, scientists in Cleveland began a long-term study of this drug. They recruited subjects and divided them into groups that were instructed to take increasing doses. More than fifteen years later, the scientists did a final follow-up with the subjects and published their results. They found that those taking the drug in high doses were eighty per cent less likely to have died compared to those not receiving the drug. It also turned out that higher dosages reliably improved the health of the subjects. The group that fared best got the highest dose, followed by those on the second-highest dose, and so it continued all the way down to those not using the drug.
. . . Okay – it wasn’t actually a drug. It was exercise.
What the Cleveland scientists actually did was put people on a treadmill and measure their cardiorespiratory fitness, their ‘physical shape’. During fifteen years of follow-ups, they found that those in best shape had an eighty per cent reduced mortality risk compared to those in the worst shape – and they didn’t find any plateau where exercise stopped mattering. Even at the very top, when comparing the ‘elite’ with those just below them, there was still a benefit to being in better shape.
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It’s generally not easy to study the long-term impact of exercise. You might think getting people to change their diets long-term is hard, but imagine getting hundreds or thousands of people to pick up a new exercise habit and stick with it for years. Due to this difficulty, most studies on exercise are correlational. In some of these studies – like the one from Cleveland above – scientists actually measure people’s cardiorespiratory fitness. But in many other studies on exercise, participants are instead asked to self-report their activity levels. To everyone’s surprise, it turns out most people vastly exaggerate how much they exercise. That makes the studies less reliable – but for once, it is in a positive direction. If people don’t exercise nearly as much as they claim but scientists still find benefits, that could mean exercise is even more beneficial than thought. And that we might need less exercise than expected to start reaping the benefits.
While quality long-term studies on exercise are hard to do, short-term interventions are more realistic. In these, exercise has been shown to induce all sorts of beneficial adaptations that we know are life-extending: improved mitochondrial number and function, improved insulin sensitivity, increased autophagy, improved function of the immune system, and so on.
Exercise is an example of hormesis, and as we’ve learned that means the benefits appear during recovery. For instance, during exercise, blood pressure, blood sugar, oxidative stress and inflammation all rise. But in the long term, exercise decreases resting blood pressure, improves blood sugar levels and decreases inflammation and oxidative stress. We adapt to the stress of exercise by becoming more resilient. However, as exercise works by hormesis, it is also clear that there must be a ceiling somewhere: some tipping point where the stress factor becomes too big. The question is whether that ceiling for exercise is anything normal people like you and I should worry about. In other words, whether you bump into it hobby-jogging a few times a week, or whether it is only applicable if you try out Race Across America or Marathon des Sables.
According to the study from Cleveland, we have nothing to worry about. Even the most active participants fared well, and we can safely live by the rule that more exercise is better. But obviously, this is one of those things where you have to listen to your body. Remember that exercise is healthy because of all the things that happen while you recover.
The traditional way to exercise is so-called ‘steady-state’ exercise. Here, you get your pulse up, exert yourself at a moderate level and remain active for long periods of time. Examples could be running, cycling, swimming or even hiking. These habits are great, but they’re vulnerable to the number one anti-exercise excuse: ‘I don’t have the time.’ If someone claims they have never used this one, they’re probably lying. A potential solution is interval training, also known as ‘high-intensity interval training’ (HIIT). In HIIT, short periods of intense activity are alternated with rest periods. For instance, twenty seconds of sprinting, twenty seconds of rest, twenty seconds of sprinting, and so on, continued for five to fifteen minutes. The aim is to reach higher levels of exertion than during steady-state exercise. This can be beneficial, as hormesis often works best with high-intensity acute stressors. Proponents believe HIIT is as beneficial as steady-state exercise, and studies tend to back this up. Among other things, a large meta-analysis has shown that interval training reduces inflammation and oxidative stress more than steady-state training – and at the same time, it also increases insulin sensitivity more. Another study has shown that interval training leads to approximately twenty-five per cent more weight loss than moderate steady-state training.
The optimal fitness regimen might include both steady-state and interval training. For instance, a runner could go jogging as usual and also sometimes do sprint intervals. However, it is important to not let the perfect get in the way of the good. Studies show that all activity is better than none, and the very best is exercising as a regular habit. That’s a lot easier if you pick something you like.
There’s a kind of mouse that would best be described as a ‘muscle mouse’. These mice have twice as much muscle mass as regular mice and also carry less body fat. They’re everything human bodybuilders dream about, without having to live at the gym or eat excessive amounts of boiled chicken. These muscle mice are extra muscular because they have defects in a gene called myostatin. Myostatin normally inhibits muscle growth, so if it stops working, muscles will grow larger. Interestingly, we also know other animals with myostatin defects: cows, dogs, sheep and, yes, also humans. In 2004, for instance, a boy was born in Germany with mutations in both his myostatin genes. Doctors described him as ‘extremely muscular’, even as a newborn. Unsurprisingly, his mother was an athlete.
Myostatin is particularly interesting to us because the muscle mice are not just extremely muscular – they also live longer than regular mice. Myostatin works similarly in most mammals, so perhaps we should be lowering our myostatin levels as well. I’m sure someone will eventually figure out a way to do this medically without side effects, and so join the Silicon Valley guys at the top of the Forbes list. For now, though, the best option is the old-fashioned one: lifting weights. One of the ways weightlifting makes muscles increase in size over time is exactly by lowering our myostatin levels.
As we age, we tend to lose muscle mass. An eighty-year-old person has lost an average of fifty per cent of their muscle fibres. This is the reason people get weaker with age – and it also decreases resilience in the face of disease. People with low muscle mass or grip strength tend to die younger, but weightlifting can help in two ways. First, if we start from a larger muscle mass, it takes a longer time to decline down to a point where low muscle mass becomes a problem. Second, weightlifting can also counteract the actual muscle loss by way of hormesis. The weight-bearing stress forces the body to invest in muscle upkeep and strengthening. Similarly, weightlifting also counteracts age-related loss of bone density. Many older people, especially older women, have problems with osteoporosis – hollowed-out and fragile bones. Again, this can be counteracted by taxing bones through weightlifting. So the conclusion is that while aerobic exercise is the most important exercise for longevity it is highly beneficial to also include weightlifting. The absolute ideal programme, if you can bear it, would probably include both steady-state training, interval training and weightlifting.