Miracle weight-loss drugs, stem cells, the aging clock, and brain health: What could extend life?

Life science and medicine are undergoing a profound and complex transformation: Artificial intelligence has begun to intervene in the key aspects of life research and drug development; gene editing is redefining our understanding of biological mechanisms and the boundaries of evolution; after the recently concluded COVID-19 pandemic, society is rethinking how to deal with sudden human disasters.

Meanwhile, revolutionary treatment methods such as PD-1 and CAR-T will turn cancer into a fully curable chronic disease within the next decade; the miraculous effects of GLP-1 drugs on diabetes treatment and weight loss may truly achieve the concept of "preventive treatment of disease", turning prevention and "consumer healthcare" to improve physical health into people's pursuit of quality of life; the approval of Aβ antibody drugs has finally brought a breakthrough in the treatment of Alzheimer's disease for humanity.

This series of scientific advancements, combined with the development of anti-aging and regenerative medicine, are changing our perception of the boundaries of life. Humans are starting to seriously consider: To what extent can life be extended?

Recently, at the "AI Gives Birth to All Things" forum hosted by the Gaoshan Academy, several high-profile guests engaged in an in-depth dialogue around the theme of "Life, Future, and Ethical Choices". The following is the edited dialogue content:

Guest Information

Lu Bai, Member of the Academic Management Committee of the Gaoshan Academy, Dean of the Shanghai Shangsi Institute of Natural Sciences

Ding Sheng, Former Dean of the School of Pharmaceutical Sciences at Tsinghua University, Director of the Global Health Drug Discovery Institute, Distinguished Professor at Bayer

David Ho, Member of the National Academy of Medicine of the United States, Director of the Aaron Diamond AIDS Research Center at Columbia University College of Physicians and Surgeons

Ning Guang, Member of the Chinese Academy of Engineering, Dean of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Wang Yongjun, Member of the Chinese Academy of Sciences, Dean of Beijing Tiantan Hospital Affiliated to Capital Medical University

Regenerative Medicine: Cells Can Be "Reprogrammed"

Lu Bai: In the past, we thought that the life process was irreversible and uncontrollable. But now, at least at the cellular level, we can "return" cells to their original state. Please let Professor Ding Sheng talk about his research.

Ding Sheng: Based on my experience in researching stem cells and drug translation over the past two decades, there have been revolutionary changes in this field.

First, the cells in our human body can be reprogrammed into cells in a very early stage of development through molecular regulation, whether it's using genetic or pharmaceutical regulatory means. These are pluripotent stem cells and the totipotent stem cells currently under research.

With such cells, based on our knowledge of developmental biology, we can differentiate them into various functional tissue- and organ-specific cells in the body for transplantation.

Traditional pharmaceutical development has a fundamental problem: Almost every new drug is non-iterative. When you develop a new drug targeting a specific target, the success rate is only about 10%; if you switch to another target, it's back to 10%. But now it's different. Through stem cell technology, combined with gene editing, we can produce multiple cell-based drugs from a single raw material, and we can continuously modify and upgrade them.

CAR-T is essentially an enhanced cell product. This means that cell-based drugs can be continuously upgraded like software. If in the future we can stably, safely, and controllably produce healthy cells to continuously replace the aging, dysfunctional, or harmful cells in the body, theoretically, we can delay aging and extend healthy lifespan.

If we further combine artificial intelligence and Brain–Computer Interface (BCI), then human longevity and even more distant possibilities are not a particularly distant future.

Will There Definitely Be Another Pandemic? Science Is Progressing, but Humans Are Prone to Forgetfulness

Lu Bai: We've just experienced a pandemic that is extremely rare in human history. It has not only changed medicine but also society itself: If another one comes, are we ready?

David Ho: I believe there will be more pandemics in the future. In the past century, we've experienced three major pandemics: the Spanish flu in 1918; HIV/AIDS, which was recognized around 1980; and the recent COVID-19. In addition, there are many "near misses", such as SARS, Ebola, Nipah virus, and Hendra virus.

These viruses have been constantly jumping from animals to humans. With the increasing population density and more convenient transportation, this situation will only become more frequent. If another pandemic comes, we will be better prepared in terms of diagnosis, treatment, and vaccines.

However, the problem is that humans tend to become slack after a crisis has passed. This is the same as preventive medicine: We always think we "should be fine" until something actually happens. The truly dangerous viruses are often airborne and infect the nasopharynx.

In addition to antibodies, we have a first line of defense: innate immunity. If we can activate this defense mechanism locally, we've seen that it can block influenza, COVID-19, and various other viral infections. Because we never know who the next enemy will be.

Is It Reliable to Lose Weight with GLP-1?

Lu Bai: Everyone is very concerned about GLP-1 (Glucagon-Like Peptide-1). It has been continuously iterated and is becoming more and more effective. Metabolic diseases, tumors, immune diseases, and central nervous system diseases are the four major diseases that have the greatest impact on humans. In the field of metabolism, will diabetes and obesity become controllable diseases in the future? Are we entering an era of preventive treatment of disease and consumer metabolic drugs? What impact will this have on human longevity?

Ning Guang: You're absolutely right. Metabolic disease drugs, especially GLP-1, have indeed entered the consumer level. Currently, in China, less than half of GLP-1 is used with a doctor's prescription. A large amount of the drug is purchased through online and e-commerce platforms. This is a phenomenon and also indicates that this drug has shifted from a "therapeutic drug" to a "consumer product".

It is estimated that by 2026, the GLP-1 market will reach $70 billion, and by 2030, it may reach $300 billion globally. So, it is no longer just a drug; it's almost a consumer product.

Everyone hopes to take it orally. But the current problem is that the absorption rate of peptide hormones in the digestive tract is too low. In the future, there may be oral regimens once a week or even once a month, and only then will it truly become an "easy-to-use drug". The main action site of GLP-1 is the gastrointestinal tract, but its real regulatory center is actually in the hypothalamus of the brain. Essentially, it is an appetite-suppressing drug. But its original function is actually to stimulate pancreatic islet secretion. If this balance is not well maintained, it will bring the risk of acute pancreatitis; as a growth factor, it may affect the thyroid; if it suppresses appetite too strongly, there will be obvious mood changes, and the risks of depression, self-harm, and suicide will increase; it may also induce ketoacidosis. Currently, a large number of people using GLP-1 are not severely obese patients, so these risks will become more prominent.

If a person gains weight, basically 80% of the increased fat is in the abdominal cavity, about 10% is in the organs, and less than 10% is under the skin. Subcutaneous fat is beneficial to some extent, but abdominal fat and organ fat (such as fatty liver) are dangerous. Currently, the fat reduction effect of GLP-1 is general. The real future direction is targeted reduction of visceral fat. There are already drugs in Phase II clinical trials targeting liver fat, but there are no drugs targeting abdominal fat that have truly entered clinical trials yet.

Why Is China a "Country with a High Incidence of Cerebrovascular Diseases"?

Lu Bai: Cardiovascular and cerebrovascular diseases are the leading cause of death in China. Why are cerebrovascular diseases particularly prominent in China? What is the relationship with lifestyle and genes? What is the relationship between cerebrovascular diseases and Alzheimer's disease? If these diseases can all be treated, do we still need a brain-computer interface?

Wang Yongjun: In China, 48% of deaths are related to cardiovascular and cerebrovascular diseases. Nearly half of the population eventually dies from such diseases. But the biggest difference is that in China, cerebrovascular diseases are predominant; in the West, heart diseases are predominant. For the same case of hypertension, in China, you may have four strokes before having a heart attack. In the case of white people, it's the opposite. After a stroke in China, 20% are cerebral hemorrhages, while for white people, it's only 7%. Our disease spectrum is very similar to that of black people.

Global data shows that the awareness rate of hypertension is completely linearly related to the incidence of stroke. The awareness rate in the United States is 80%, so there are fewer strokes; in China, the awareness rate is moderately low, and the number of strokes is high; in some African countries, the awareness rate is less than 20%, and the number of strokes is even higher.

The reason is that the Chinese have insufficient intake of fruits and vegetables; combined with air pollution, blood vessels are damaged over the long term, resulting in this situation.

Even if stroke and Alzheimer's disease are cured, brain diseases will still be the most prevalent. The latest European data shows that €800 billion is spent on brain diseases every year, which is equal to the total spending on all other diseases combined. From birth to old age, the brain is constantly "sick". 80% of single-gene diseases in the whole body occur in the brain. In recent years, the incidence of childhood autism has increased significantly; many teenagers suffer from insomnia. There are about 100 million migraine sufferers in China, mostly women; after adulthood and starting work, various diseases such as depression and emotional disorders emerge; in old age, cortical aging brings Alzheimer's disease; subcortical aging brings Parkinson's disease; aging of the anterior horn cells of the spinal cord brings amyotrophic lateral sclerosis (ALS).

Wherever there is aging, there will be problems.

In addition, the brain has two fatal weaknesses. First, it is the only organ without energy storage. 15% of the blood supply to the heart and 20% of the body's oxygen are supplied to the brain. Second, the brain's regenerative ability is almost the weakest in the whole body. Even though it has been discovered that neurons can regenerate, their role in overall recovery is still very limited.

The world has regarded "brain research" as a national asset. The G7 Summit proposed Brain Capital: A country's future competitiveness comes from mental power, not physical strength. Thus, there is Brain Economy. Now there are scientific methods to evaluate the degree of brain aging and predict the risks of stroke, dementia, Parkinson's, and ALS. Most brain diseases can be prevented. It is recommended that everyone go to the hospital for a brain health assessment as early as possible.

Q&A Session

Q: There are many "clocks" in the market to measure aging, including those for the brain, organs, and DNA methylation. Many of us have sports equipment, smart bracelets, and various medical examinations, which will all give you a biological age. My questions are: First, which method is the best? Second, how should we understand biological age? Is there a better measurement method?

Ding Sheng: There are indeed a large number of methods, such as DNA methylation, gene expression panels, protein modifications, etc. But to tell the truth, the vast majority of research has been done on animals. In the human population, especially at the clinical intervention level, there has not been unified verification.

However, with artificial intelligence deeply learning the aging-related data generated by more measurement methods, combined with the emergence of drugs or consumer products like GLP-1 that can potentially intervene in certain indicators, we have truly entered a stage: a stage where we can start to evaluate and intervene in the "age state". A great deal of resources will be invested in this area in the next few years.

Q: Should I get a stem cell injection?

Lu Bai: Anything that has not been approved by the drug regulatory authorities can only be considered "just for fun". This concept is very important. I know many people here have gotten stem cell injections. If you're getting it to treat a disease, then it must be a drug. But a drug must meet three basic criteria: randomization, double-blindness, and placebo control. It must go through clinical trials and be approved by the drug regulatory system. Otherwise, it's not a drug.

Getting a stem cell injection is the same as eating a piece of braised pork: You may feel better, but that's not treatment. As for artificial intelligence and big data calculating a "brain age" or "immune age" for you, as far as I know, none of them have been approved by the drug regulatory system.

Q: What are the reliable and effective "aging indicators"?

Ning Guang: In the field of aging, biological aging is a very important concept. I have a few indicators for your reference:

The first indicator: Body weight

Can you maintain a constant body weight in the long term? Think about how much your current weight has increased compared to when you were 20 years old. Why is it important to maintain body weight? Because as people age, especially after 60 years old: Weight gain mainly comes from fat; weight loss comes from muscle and bone. After 80 years old, the overall body weight is decreasing, but abdominal fat and organ fat increase significantly. So if your weight is still increasing significantly after 60 years old, it can basically be judged that the increase is all fat. And the incidence of cardiovascular and cerebrovascular diseases and tumors increases with the increase of fat.

The second indicator: Sleep

As people age, if your sleep becomes shorter and irregular, this is a very important signal. This change usually occurs after 50 years old.

The third indicator: Falls

After 70 years old, have you had a fall? Because a fall after 70 years old is very likely to lead to a fracture, and the treatment after a fracture will cause damage to the brain. You can use these three indicators to assess yourself and your family members.

The fourth bonus indicator: Genetics

If your parents can live to 90 years old, you can basically live to 95 years old.

Q: How to ensure brain health?

Lu Bai: Stress is the biggest enemy. Stress is number one killer for your brain. Whether you're starting a business or doing investment, stress management is an extremely important part of brain health.

Wang Yongjun: Currently, there are many brain health and brain training clinics in Europe and the United States. They first measure three things about the brain: Is the structure normal? Is the function normal? Is the social adaptation good? What does it mean for the function to be normal? The most core is the ability to resist stress. During the pandemic, when people got COVID-19, some had brain fog, while others didn't. People with brain fog indicate that