Willa Mag

Science has too many unsolved mysteries. What exactly is dark matter? Why do humans have consciousness? Are we the only living beings in the universe? And... why do I always feel so tired?

Adult fatigue is indeed a difficult and frustrating problem, and it is also an issue that concerns the daily lives of many office workers. According to a previous analysis of data from 32 countries, as many as one-fifth of healthy adults have reported being overly fatigued. Persistent fatigue is one of the most common reasons for people to seek medical advice, and doctors usually refer to it simply as TATT (Tired All The Time). In most cases, it is difficult for us to give a clear medical explanation for the cause of fatigue, and doctors can do little apart from conducting blood tests to check for obvious factors such as nutritional deficiencies.

Although the problem of fatigue places a huge burden on public health, the medical community seems to have never delved deeply into the biological essence of "energy" and "vigor" or explained the true meaning of being "energetic". In recent years, the health industry worth trillions of dollars has entered this gap - providing countless ways to enhance human vitality through various supplements, diet plans, and lifestyle adjustments.

In recent years, scientists have rethought the meaning of being energetic and explored the essence of fatigue and a sense of powerlessness. Some studies have shown that our perception of our energy state largely depends on the brain's continuous assessment of the available energy in cells. This discovery is changing our understanding of overall health, opening up new avenues for treating clinical-level fatigue problems, and putting forward some practical suggestions - perhaps helping those who feel "burned out" to regain the vitality of life.

It is obviously a very strange situation from the perspective of calorie balance that so many people with no physical problems feel completely drained. If whether you are energetic only depends on the level of calories you consume and expend, then modern people, who can easily consume far more calories than their bodies need, should not have any fatigue problems.

So what's the crux of the problem?

In short, the energy/vigor we can feel, or "subjective vitality", is not simply a reading on a fuel tank; it is a comprehensive and well-founded continuous assessment by the body and the brain: How much available energy does the body have? How much energy has been consumed? Is the remaining energy sufficient for the next task? These dynamic predictions dynamically determine our energy level.

Why do people feel sleepy and exhausted even when they have stored too much "grain"?

The above perception of energy is an example of what is called "interoception". Interoception refers to the ability to perceive internal signals of the body to understand one's adaptability to the external world. If there is a problem, such as the body feeling a lack of energy, these signals will prompt us to take action to solve the problem. Scientific research on interoception shows that human feelings, emotions, and motivations are all based on the continuous and ever-changing dialogue between the body and the brain.

Energy is the product of this dialogue process. From this, we can understand why simply eating more food or taking supplements is not enough to increase our energy level; we need to figure out where the signals about energy conservation come from in the body-brain dialogue and then solve the problem at the root.

Perhaps the problem lies in the energy release of cells. Perhaps the brain anticipates certain physical and mental challenges and thus actively reserves some energy for future needs. It is also possible that factors such as stress or infection have occupied too many body resources... Whatever the reason, the result is that you are drained. Of course, we need to eliminate fatigue by addressing the root cause.

The concept that energy is the core of health has a long history. Thousands of years ago, the traditional Eastern medicine was established on the basis that "the flow of human energy is the foundation of health and vitality". However, the cornerstone of Western medicine development is anatomy and physiology - everything must be visible, measurable, dissectible, and treatable with drugs or surgery. It is understandable that traditional Western medicine ignores this intangible force of energy flow.

The Western medical approach has extended human life expectancy by 30 years in less than a century, which is undoubtedly a miracle, but it has not significantly increased the time we can enjoy a healthy life, that is, the so-called healthy lifespan. According to an estimate in 2021, the global population now has to endure about 9 years of illness on average.

Martin Picard of Columbia University in the United States points out that it is time to shift the focus of medical research from disease treatment to understanding the essence of health. The key lies in a deep understanding of the way energy flows in the body.

Having the tools of reductionist science has led us astray. If something cannot be sequenced, observed under a microscope, or measured on an oscilloscope, it is not a suitable research object. I think this mindset has made us miss some really valuable things."

Picard once studied under Doug Wallace, a pioneer in mitochondrial research and a geneticist. Mitochondria, as the "factories" of cells, convert food molecules into chemical energy that can be used by cells. Wallace and others found that when mitochondria do not work effectively, people will feel sleepy.

Based on this discovery, Picard founded a new field, mitochondrial psychobiology, aiming to explore the two-way relationship between the "energy of mitochondria" release and "the degree of vigor we feel". Other studies have shown that healthy people may also encounter mitochondrial problems due to many factors, and some of these factors are almost certainly the driving forces behind the prevalence of TATT.

For mitochondria, an excess of fuel may actually lead to the greatest energy loss. The mechanism of this absurd situation may be that mitochondria release energy gradually through a series of delicate biochemical steps. If too much fuel is consumed at once, they have to suspend energy production so that the cells can focus on storing the excess energy for later use - which actually leads to a decrease in short-term available energy.

The harm of a high-sugar diet is particularly significant. Studies have shown that a high-sugar diet can lead to low mitochondrial efficiency, causing emotional problems and fatigue. Interestingly, if you choose a ketogenic diet, which is low in carbohydrates and high in fat, to significantly reduce sugar intake, this "challenge" to mitochondria may have the opposite effect.

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In addition, stress, whether it is from the emotional level or physiological problems such as infection or trauma, can affect the energy state.

Picard and his colleagues previously investigated and found that stress can increase the speed at which cells consume energy by 60%; partly because mitochondria also secrete the stress hormone cortisol, which sends a signal that "energy is needed to deal with challenges".

Stress not only erodes energy but also disrupts the body-brain energy calculation on a broader level.

Lisa Barrett, a neuroscientist at Northeastern University in the United States, once proposed the concept of "body budgeting" to describe the key role of the brain in managing energy supply to maintain survival. The working principle is as follows: The brain generates a "best prediction" of the external environment and then makes adjustments based on sensory feedback. When the prediction does not match the evidence, this error signal will be converted into physical sensations of being good, bad, fatigued, or energetic. "We regard these as an overall overview of the body's metabolic state."

Importantly, the brain's assessment of the metabolic state can explain why even with sufficient sleep, just thinking about a difficult task waiting for you can make you feel fatigued; it can also explain why unexpected good news can make you instantly full of energy. The actual energy reserve of the body has not changed, but the brain's prediction of available resources has changed the perception of energy.

A study led by Arran Davis, an expert at the University of Oxford, shows that the above predictive power has a significant impact on human energy consumption. Suppose a person is required to exercise until exhausted. If he can get support from friends during the process, he can坚持 exercising for a longer time and burn more calories before exhaustion.

In Davis's words, when the brain is convinced that someone is providing help, it can dig deeper into the body's energy reserves. "Social support indicates that there are enough resources around to help with recovery, so we can use body resources more easily."

In fact, in the body-brain energy assessment process, the input signals are very complex. Some are physiological, some come from the psychological level, and many operate unconsciously. Therefore, it is a daunting challenge for scientists to objectively measure the sense of fatigue. However, there are several "biomarkers" that can be used to reflect physiological processes and subjective vitality or fatigue.

One is growth differentiation factor 15 (GDF-15). This is a metabolic signaling molecule released by cells under stress; the release reaction is triggered when the body encounters infection, tissue damage, or mental stress.

Stephen O'Rahilly, an endocrinologist at the University of Cambridge, says that GDF-15 seems to be a general distress signal that can tell the brain to save energy.

GDF-15 may also explain why the problem of fatigue worsens with age. GDF-15 is a reliable marker of aging, and its level in the blood increases by 25% every decade.

Picard speculates that this is also related to energy budgeting. He published a paper in 2024, pointing out that many aging symptoms, including fatigue, are due to the accumulation of damage in cells, and the energy required for repair is too high.

When metabolic waste accumulates, cells send a distress signal to the brain, triggering a whole-body energy-saving mode. Picard explains: "GDF-15 will loudly announce that there is a metabolic overload here, requesting to cut expenses, atrophy muscles, suppress passion, and turn hair white. These are all strategies to save energy."

Scientists have also focused on many other different biomarkers.

In 2021, the World Health Organization convened a group of experts in health and aging research to develop a new definition of health: The basis for judging health is not "being free of disease" but the so-called "vitality capacity", that is, the body's ability to extract enough energy from food to maintain good operation.

The expert team explored several indicators that are expected to be used to evaluate the level of health and vitality - from muscle strength to blood inflammation markers, and then to simple self-state assessments. One promising method comes from the doctoral research of Ivan Bautmans, a gerontologist at the Free University of Brussels in Belgium and one of the team leaders, 20 years ago: simply testing the speed of muscle fatigue with a handheld device.

This device can calculate how long it takes for someone to lose 50% of their maximum grip strength when squeezing the device with all their might; combined with a questionnaire about the person's current energy level, a total score can be obtained, thus presenting their physical and mental energy levels to a certain extent.

Bautmans says: "This is a surrogate indicator that can reflect whether physiological functions are imbalanced or malfunctioning."

A survey of nearly 1,000 middle-aged people shows that those with the lowest total scores are more likely to have biomarkers of low-grade inflammation in their blood compared with those with higher scores. This is very important because chronic inflammation is a known driver of aging; another question then arises: If we receive enough warnings and give the correct interventions, can we delay the aging process itself?

Your hair turns white as you bear the stress, I exercise, but who gets younger?

A study conducted by Picard and his colleagues offers hope. He had heard anecdotal reports that sometimes white hair would turn black again from the roots. Interested in this, Picard recruited 14 volunteers who had experienced this to participate in the survey. Finally, he found that the stressful periods in their lives seemed to be related to the stage when their hair turned white; and when the stress disappeared, the white hair turned black again.

Picard believes that this phenomenon is due to the body-brain system temporarily diverting the energy originally used for hair melanin synthesis to more urgent tasks. "When the stress is reduced, a part of the energy budget is released and returns to the 'hair dyeing' work."

Of course, this does not mean that the natural process of hair turning white with age can be reversed. But we do see that the speed of aging is more plastic than we previously thought.

Regarding fatigue as the result of the dialogue between the body and the brain also provides a new perspective for understanding chronic fatigue syndrome (CFS, also known as myalgic encephalomyelitis). The symptoms of CFS are difficult to explain. A deeper understanding of the pathways involved in this syndrome will help doctors identify the problem areas. For example, previous studies have associated CFS with various factors, including: reduced blood flow, leading to a lack of fuel for mitochondria; chronic inflammation, consuming the body's reserves; and a bottleneck in the interoceptive processing center involved in energy budgeting, that is, the brainstem.

With the new understanding of energy and vitality, we can also formulate new strategies to deal with fatigue in our daily lives.

One option is "deep rest" proposed by Elissa Epel, a psychologist at the University of California, San Francisco. Epel has studied the psychological benefits of contemplative practices such as meditation and prayer. She believes that one of the reasons why such practices enhance well-being is that they can bring physical and mental peace, making the brain less eager to seek defensive contraction and reserve energy.

Diet and exercise also affect our energy distribution. Sugary snacks have been proven to cause emotional and physical problems by disrupting mitochondrial function, while so-called "exercise snacks" can have the opposite effect. Regular and regular exercise can force the body to improve energy production efficiency by removing old and inefficient mitochondria and generating new and efficient ones.

It is worth noting that the people around you will actually affect your own energy level! Therefore, no matter how busy you are and whether you occasionally fall into the "abyss" of not being able to control your diet and not wanting to exercise, we can still be glad that humans are social animals, and our physical and mental states are highly connected to the social environment. There is always someone who can give us a hand!