What mechanisms and targets are the forefront trend?| Pharmaceutical Cond Health Aging Forum Record

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What mechanisms and targets are the forefront trend?| Pharmaceutical Cond Health Aging Forum Record

2022-01-15 18:07:29 13 ℃

Editor's note: Recently, the first Pharmaceutical King Health Age Forum opened online, from the United States, Europe, Singapore, China and other places, affiliated industrial, academia, venture capital, government decision-making layer Global leader copagon, explore how everyone can have a longer and healthier future.

In order to facilitate more new and old friends, the revision of the expert cave, the drug in Cantonese Content Team continues to launch the text record discussed in the forum. The third discussion topic is "the current situation of aging research". More reports, please pay attention to "Pharmaceutical King" public account.

Due to the retroception of the country, the understanding of aging biology will specify the scientific direction for anti-aging strategies. This discussion of the Medicine Health Age Forum will give a look at the forefront of aging research. Outstanding researchers in the three aging areas will share the latest insights on aging and disease process from biological perspectives, and their enlightenment to therapy development and target recognition. A number of anti-aging therapies have begun to get into clinical, and the flourishing development of this field is worth looking forward to. In addition, three experts also strongly appeal to healthy lifestyles is also an important choice for anti-aging.

Solve aging, perhaps to prevent multiple diseases at the same time

Dr. Sebastien Thuault: Hello, thank you for watching this topic discussion on aging research status. I am the editor of Nature Aging Sebastien Thuault. "Nature - Disease" is a journal in publication of biological health, social science research papers, as well as comment articles on aging and age-related diseases. I am very honored to introduce you to the two guests participating in the discussion today. They are outstanding researchers in the field of aging, from Dr. Linda Partridge, Max Prance Diseases, Germany, and Eric Verdin from the US Buck Institute. PhD. Linda, ERIC, welcome two.

Dr. Sebastien Thuault: As an opening, I would like to introduce it, why is it important to the study of aging and longevity. Due to the advancement of modern medicine, now many of our lives are much longer than before centuries, and the world is also in progress. In human history, the number of populations over 65 years old exceeded children under 5 years old. It is estimated that by 2050, about 20% of the population will exceed 65. This aging process has brought both challenges and opportunities. For those who have a good health condition, the opportunities brought by aging include continuing to work and share knowledge, volunteer work, take care of their families, share wealth, contribute to society in a variety of other ways. But the prerequisite for these opportunities is health.

Unfortunately, longevity does not necessarily mean good health. Most older people have a variety of diseases, such as cancer, cardiovascular or metabolic diseases, dementia, arthritis, etc., which brings health, economics and social challenges with age-related multi-disease conditions. Therefore, achieving health aging should become the primary task of society. To get the so-called "longevity bonus", this is a major challenge we have to solve.

Obviously, understanding of aging biology will help us extend human life and health life. Speaking here, I would like to ask the first question. From the perspective of biological perspectives, what is aging? What is aging on the biological level? Linda, can you please share it?

Dr. Linda Partridge: Since these years, the culprit in the aging process has become very clear. It begins with problems, DNA damage, and the like, which are caused to deteriorate the mechanism of the entire control gene expression. This also means that the protein in the cell has begun to deteriorate, and the control of protein quality is often affected. Differential disorders in mitochondria for cellular energy supply, aging cells begin to accumulate. This is very important in aging. These cells can resist apoptosis, with strong bioactivity, and can lead to tissue damage.

Stem cells begin to abnormally, there is no split when it should be divided, or if it should be divided while should not split, the wrong divided sub-cell cells. Systemic inflammation occurs during aging, resulting in deterioration of the entire circulation environment. The reaction of cells to normal nutrition and signal molecules circulating in the system also become very poor.

So this is very complicated, there are many things happening, and not independent. For example, gene injury can lead to cell aging, which leads to most animals that will appear with age-related inflammation during aging. It is now clear that we can fight some basic mechanisms of aging. Therefore, it is important to identify them to improve health in the process of aging.

Dr. Sebastien Thuault: ERIC, do you want to add it? Perhaps you can talk to our influence of this biological process on age-related diseases.

Professor Eric Verdin: In the past 10 to 15 years, there have been an expected thing, that is, when we study the basic mechanism of aging, we not only created animal models, but also observed various model animals. Live longer, and healthier. This does tip us, aging is not only a process of restriction life, but it also contributed to the concept of "healthy life". Recognizing the same mechanism behind the aging process with the actual mechanism of the actual driven disease process in the aging process, this has indeed changed our views on aging. This concept is called "old science". This view believes that aging is a major risk factor in a series of chronic diseases. In fact, as the population is aging, we are experiencing the popularity of these diseases. This work has extremely important sociology and scientific significance, which means that when we consider using this basic biology research to human beings, one of the early priorities is to apply old science to improve our aging process regulation pathway. To mitigate or inhibit the development of aging chronic diseases.

Sebastien, you mentioned these chronic diseases we are familiar with, such as Alzheimer's disease, Parkinson disease, cardiovascular disease, heart disease, stroke and many forms of cancer, all consume our social resources, It really restricted the quality of old life. Therefore, many of our current focus is actually trying to struggle with these diseases and change our views on aging.

Dr. Linda Partridge: Yes. The potential mechanism of these aging is present in these age-related diseases - they are indeed the main cause. If we can solve them, we may prevent multiple diseases at the same time.

New discovery and new trend of anti-aging research

Dr. Sebastien Thuault: This is a very interesting concept. In my opinion, aging research is indeed a booming area. Important discovery will be released every week. Can you tell us that some new discoveries recently causing you, this may explain some current trends in the field.

Dr. Linda Partridge: The current is indeed a very active area. There will be some very interesting things in the study literature. I started my own scientific career as an evolutionary biologist. I am very interested in these creatures living in nature - that is really longevity. Recently, Greenland sharks can live 400 years, it is really amazing! The small double shell of the Atlantic Ocean is 500 years. There are some very long livelihoods. People have always tried to find this potential reason for slow aging, can we learn from these creatures, help us improve human health in the end of life?

Recently, there was a paper about rock fish caused my attention. There are many kinds of rock cavity in the world, some of which can live to 200 years, and some can only live for two years. Obviously, a large genetic difference in the speed of aging and the resulting life. In this paper, in this paper, the genome of all these rock fish is sequenced, trying to find the evolution tree of all these species, how they are interrelated, and the longevity in some species is in the evolutionary tree Is it independently evolved in different branches? The results prove that the latter is correct - they have experienced many independent evolutionary transitions, thereby achieving real longevity.

This is part of an ecological reason. For example, longevity species tend to live in the deep sea, and they are also very small in the first reproduction, and these conditions are related to considerable genetic variation. Interestingly, once they excluded, the genes in the nutrient-sensitive network will also be associated with the longevity characteristics of these species, such as insulin, IGF, Tor, and these factors have also proven to be very important in laboratory research. In addition, there is a feature of inflammation-related gene amplification, both of which are very obvious.

In some respects, the results of this papers are very inspiring. It reminds us to work through our laboratory and laboratory model bio - yeast, worms and fruit flies, we are using these widely known model organisms to reveal some of the most basic mechanisms. It turns out that these mechanisms are very important in the evolution of natural longevity organisms.

Dr. Sebastien Thuault: Can I tell two sentences next question? In fact, this journal has recently published a papers to study the genetic factors affecting the longevity of the 100-year-old. As you mentioned, some insulin-related mechanisms and all the biological mechanisms we have learned from other organisms have appeared in those analyzes. In this way, this biological mechanism seems to be able to convert and apply to human groups.

Dr. Linda Partridge: Research on this field is ripening. The target that improves the health of the elderly needs to pay attention is more and more clear. It can be clarified that inflammation is a great influencing factor. A paper that I liked recently studied excessive reactions in the process of innate immunization. Studies have basically confirmed the new metabolism of macrophages, which are increasingly relying on glucose. At the same time, they also increase the expression of a receptor, which transforms glucose into glycogen stored, hindering the call to glucose or the respiratory process. After inhibition of such receptors from genetics and pharmacology, researchers have improved good energy supply, and reducing proximity. More importantly, this process reduces cerebral inflammation, which is very important in neurodegenerative diseases. Even in elderly mice that have already appear eutea, this drug inhibitor is given, they still restore special memories and obtain long-term hippocampal enhancements. This is a very great study.

Dr. Sebastien Thuault: It's really interesting. Eric, what have you been to study your research recently?

Professor Eric Verdin: I want to call the views mentioned just mentioned. Chronic inflammation is becoming one of the main participants, and this topic has been ignored. For example, (now) chronic inflammation is no longer included in the first nine features of the aging. The aging field is now found to have the importance of inflammation.

Professor Laura Niedernhofer from University of Minnesota has recently published a papers in a key research strategy. They knocked out genes encoding DNA repair proteins, ERCC1, who conducted this step in tissue-specific ways, and cleared this gene in all hematopoietic cells. Hematopoietic cells are located in the bone marrow, which can produce almost all blood cells, macrophages, neutral granulocytes and lymphocytes.

By selectively knocking out DNA repair mechanisms in these cells, they want to induce accelerated aging processes throughout the lymph and myeloid system. Researchers observed that this did shortened (mouse) life, indicating that only the aging of the immune system itself can cause the body to aging. More interesting is that they observed the appearance of secondary agents in multiple organs, indicating that the aging myeloid and lymphocytes circulating in these organs can induce secondary age of these tissues. Although this does not prove chronic inflammation is the only mechanism, it does point a fact that the aging in this area occupies the dominance in the entire biological aging, so this is probably a very important target.

Another paper I want to emphasize is also from the University of Minnesota, from the Professor Paul Robbins. This study is related to COVID-19, this is very exciting. We have observed that the age is the main risk factor for complications after new crown virus infection. It turns out that the aging mechanism is the culprit. In the paper, researchers use a coronavirus mouse model, not a new crown virus, but another mouse-specific coronavirus. Studies have shown that under normal conditions, the mortality rate after infection of this virus is close to 100%. The post-researchers gave these elderly mice anti-aging drugs (SENOLYTICS), or using a variety of genetic means to remove aging cells, the study found that only these changes, thoroughly changed the disease process, and made a considerable number of mice survived .

This means that although it is not confirmed, in the human group, (aging mechanism) is probably one of the mechanisms that cause the elderly more susceptible to bad results. In addition, when we evaluate the risk factors of COVID-19, not only the elderly people, including the basic diseases we are talking, but also a lot of chronic diseases related to aging. This emphasizes that age is obviously a big risk factor, but if there is other age-related diseases, the danger will increase - this is of course also obese. The significance of this research work is significant because we are in the new crown epidemic, but if we look back in the flu, the situation is completely compliant.

We spent some time to review the literature, discovering the risk factors of age and influenza. I want to remind everyone that now, nearly 4 to 50,000 people will die in flu each year. Finally, I would like to say that we know that with age, the vaccination rate is declining, which means that groups that have been at the highest risk may be the least response to the vaccine. This is very interesting. We have a very large investment in this field. We tried to understand how the aging mechanism changes or regulates the human body's response ability to vaccine, and looks forward to revealing the signs of aging through our interventions to discuss, thus trying to alleviate us in the elderly. The adverse reaction of the vaccine seen in the person.

Challenges and future directions of transforming medical research

Dr. Sebastien Thuault: This is a great example. Significance. In this context, how do we apply rich biological knowledge to improve human health? Is these transformation works successfully? Is there a challenge, what is these challenges?

Dr. Linda Partridge: Our life is so long. We now know what problems in the process of aging in the process of aging. We also know that you can intervene, through drug treatment, metabolites, gene regulation, lifestyle, and nutrition, we know these basic principles. To apply it to humans, we need more people and many people are also getting a point of research results, that is, (find) a good biological marker. We need some things to prove that if we try to use a new drug in humans, they have responded to some way, indicating that we target the correct target to make them more in life. healthy. People are trying to explore, such as DNA methylation, histone modifications, circulating metabolites, RNA transcriptions, and other technologies such as protein markers, inflammatory markers, etc., try to understand what the human beings are in aging process.

Of course, individuals with aging process are very different, and different individuals will have different problems. Different organs will affect different organs during aging. We need a shortcut to determine what problems have occurred during the aging process, as well as whether specific interventions will improve. For so-called "aging clocks" is carrying out a lot of interesting work: what makes them slow, what makes them accelerate - this is very helpful, this is what we really need.

Many of the current drug interventions tend to change the adaptation of existing drugs, and make a larger-scale population trial for a new drug that is agreed, this will be very difficult. Although the US FDA decided that aging was the effective study of clinical trials, the research cost is huge.

Many working works represent drugs that have already been used for nutrient sensing networks, which can improve mitochondrial function and so on. Based on aging characteristics in the illness of disease disease, they plan to study whether these therapies can be reused to prevent disease. I think it is necessary for new drugs that need to be customized for specific indications. For example, ERIC has been mentioned in anti-aging drugs.

I think this will be very important, systemic new therapy can be very toxic. However, their applications may be more effective when applied to specific parts, such as eyes and joints. Therefore, I think these are both challenges and are currently in a field that is currently improving.

Dr. Sebastien Thuault: It sounds exciting. Eric, what do you feel?

Professor Eric Verdin: I agree with Linda's point of view. In this research field, we live in an extraordinary era. From a major study, it has been found to be used in clinical practice, usually take 15 to 20 years. Interestingly, as an indication, aging brings a series of challenges, we do not have to be treated as drug developers. When I was studying in the medical school, I learned the first thing that Hippocra has vowed: "First, don't cause harm." This means that care must be difficult to make it difficult and need to ensure that all aging related interventions will not cause harm.

Unfortunately, many drugs have potential hazards, especially when they use long-term medication. Therefore, this has indeed promoted a field to develop in multiple directions. At present, we are still not sure how this will develop.

Obviously, people have changed the attitude towards aging, and it is considered that aging is a disease, or a disease that can be treated. A good example is the Tame (TARGETING AGING BY METFORMIN) of Nir Barzilai and his colleague. Take other health adults to evaluate their anti-aging ability within a certain period of time.

Dr. Sebastien Thuault: This is a new example of old drug mentioned by Linda, because metformin has previously used to treat diabetes.

Dr. Linda Partridge: Dimethium, of course, is a safe drug.

Professor Eric Verdin: Yes. The application of hundreds of millions of doses shows that this is a safe drug. A epidemiological data show that patients with diabetic diabetes, can prevent some diseases, such as type 2 diabetes, certain cancers, and neurodegenerative diseases. Therefore, metformin looks like an anti-aging drug, but the anti-aging effect in the non-diabetic population has not been confirmed. This is why clinical trials are important. This is a way to see drug development.

Another method is to identify specific conditions related to the aging, these conditions have not been mentioned in the past, and even have not been identified. The individual conditions may lead to a faster drug development pathway.

I will take a few examples, one is muscle reduction, that is, the muscle mass associated with aging declines. The other is the thymus degradation, that is, the thymus loss after the sternal, the thymus is a key organ of T lymphocyte development, which will shrink with age growth. Another example is that the vaccination of our previous vaccination is insufficient. In fact, many of this is being studied separately. Finally, Linda refers to eye disease, macular degeneration, glaucoma, which seems to have treatment potential for aging cells to target these diseases.

At present, the biotech companies in this field are exploring these different ways, we will wait and see. We have not given a medicine to delay the idea of ​​aging. We are closer to this point of view that people with rapid progress of aging risk or show agreed symptoms will become a targeted population of specific drugs. Sebastien, I hope to wait for the chance to discuss the change of lifestyle, I think this should not be forgotten, because this is the first line of evidence of aging.

Healthy lifestyle is our existing anti-aging "therapy"

Dr. Sebastien Thuault: Of course! These efforts you mentioned are indeed a pioneering in the field of transformation. So far, our conversations are mainly concentrated in biological knowledge, which can help us delay the aging process.

We know that some lifestyle choices help achieve health aging and longevity, and help solve the challenges of some population aging. So let us talk about it.

Dr. Linda Partridge: Two key are sports and diet. A person can improve health in any age, depending on what stage. The huge unequal health during the modern society, often comes from these two simple questions. Other smoking, proper control of weight, avoid metabolic diseases and complications, exercise to maintain heart health, prevent muscle reduction, etc.

These are very simple and effective interventions. But in some countries I are familiar with, these are not standard public health measures. They only appear in an obese intervention strategy, not aging. It is a simple intervention for the elderly to open a regular dance class. People who have any ages like to dance, this is a great movement, and affordable and simple. But outside East Asia, there is almost no country to take these interventions seriously. They should be taken seriously.

Professor Eric Verdin: I agree with this point. Linda, I will give a few examples to further strengthen your point of view. One thing is that everyone is not realized, that is the importance of lifestyle on their expectancy. Many people have a view of the obstacles that will happen.

The Calico Group has recently published a paper that studies the relative contribution of genetic factors and lifestyle factors. Although the value of this papers is different, I think a signal from them is that nearly 90% of the expected life is determined by environmental factors, lifestyle, etc.

I think this is a strong signal that needs to make people know that the expected life depends mainly. In essence, you can't blame your parents because of the problems encountered, although there are some genetic effects.

We also learned from epidemiological data and society. In the same city, there is also an amazing difference in life, sometimes in the United States and Europe. The average life expectancy of the poor is 67 years old, and the rich people with high education can live to 87 years old. The expected life has a gap between 20 years.

We know that these differences are caused by many factors. I am convinced that education is a very important factor that provides people with truly effective information. Other of course, there are physical activities. I don't like to use this word. I think physical activity is enough to become a key. Nutrition is also a very important factor, which is closely related to our biological understanding of aging, pressure, and sleep.

Finally, our research field can still make great contributions. I think the drug that can slow down the aging process is being developed, which will become available. But today you can do is in the best physical condition when the drug is about to be listed.

A good example is exercise or physical activity. People lack a lot of knowledge in "what should be doing". People think I have to go to the gym and have to sweat. And if you don't like it, I don't do anything.

For example, we know that walk is a magical anti-aging therapy, which may be the best therapy we have today. Some people say that if you can make it into medicine, convert it according to the value of existing drugs, it will reach 20 billion US dollars.

Even when we think of walking, many people will think "I have to take an hour and a half hours, walk 10,000 steps." There is a study that is not long ago, focusing on the influence of walking steps on the expected life. The significant discovery of this study is that it is taken 4,700, that is, about 25 minutes walk, you can get nearly 70% of physical activity. As LinDa mentioned, I think this should be part of a wide range of public policy efforts.

I am sometimes confused. We put huge amounts of funds in health care, and there is very little spending in prevention. I hope that our research field can return to the foundation, telling those people who decided, this is the most worth value.

Dr. Sebastien Thuault: I agree. There must be necessary to promote these policies and improve public health, and we have known effective methods. Our discussion is coming to an end. Thank you for contributing this humorous dialogue. This is a very exciting moment for this field. We can see how this study has caused so much impact - not only in our understanding of biology, but also has an impact in clinical and social fields.

Investment in aging research is to invest for our own and future generations.I am very expected to witness the sustainable development of this field.Thank you again.Disclaimer: Pharmaceutical Content Content Team focuses on the introduction of global biomedical health research progress.This article is only the purpose of information exchange, and the viewpoint does not represent the Pharmaceutical Kangde position, nor does it represent the support of Cantonese British or objection.This article is not recommended for treatment.For guidance from treatment plan, please visit the regular hospital.

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