Interview with George Church - Is End of Aging Near

Original author: Gregory M. Fahy, PhD
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Foreword by Gregory Faye


As a biogerontologist, I have been attending scientific meetings on aging since the early 1980s and have seen and heard many amazing things. But when I attended the George Church lecture at a conference organized by the SENS Aubrey de Gray Foundation at the end of 2014, I realized that I had just heard the most wonderful lecture in my life.

Why? For three very simple reasons.

First, as Dr. Church emphasized in the lecture, aging seems to be largely controlled by the action of a small subset of your genes, and mainly by master genes that control a large number of other genes. Your genes are areas of your DNA that determine your eye color, hair color, gender, height and other characteristics of your body. But it is becoming increasingly apparent that genes also determine how you are aging , and perhaps whether you are aging at all.

Secondly, Dr. Church talked about how technology has advanced to such an extent that the activity of your genes, whether on (expressed) or off (not expressed), is becoming more and more controlled. And this is possible not only in vitro, but throughout the body, and even in the brain.

Dr. Church's focus is on CRISPR ( clustered regular intermediate short palindromic repeats ), which is a relatively new and very powerful method for regulating gene activity.

CRISPR can “edit” or modify genes to correct harmful mutations or create intentional mutations that can have a positive effect (for example, turn off genes that affect aging). Thus, the connection is very clear: if aging is controlled by master genes, and if the activity of such genes can now be intentionally controlled, then we are starting to approach aging control at a fundamental level. And the same technology can be applied to the correction of many diseases, no matter whether they are age-related or not.

Finally, our ability to control aging would be completely useless if we had no desire to use it in real medicine. Fortunately, Dr. Church wants his achievements to quickly be in clinics. He intends to make aging control a practical reality - and very soon. And Dr. Church, as an outstanding professor of genetics and a major figure at Harvard Medical School, has every opportunity to realize his wishes.

In an interview with the Washington Post in early December 2015, Dr. Church said his lab had already reversed aging in mice, and human trials could take several years to complete. Dr. Church stated:

“One of our biggest economic disasters now is our aging population.”

“If all these gray-haired guys could return to work and feel healthy and young, then we would have prevented one of the greatest economic disasters in history.”

He said he sees:

“A scenario [in which] everyone receives gene therapy, not only to treat rare diseases like cystic fibrosis, but diseases that everyone has, including aging.”

Dr. Church also mentioned his personal interest in reversing human aging when he stated:

“I want to become younger, I still try to do something new every few years.”

CRISPR technology can change the world and our lives as we know them.

CRISPR is a technology that originally emerged in nature to fight viruses by cutting their DNA. Fortunately, it has now been modified by scientists, and can make specific controlled changes to the right places in the genome. As soon as doctors can adjust or “edit” the DNA, they will begin work to restore youth in older people.

How serious is the promise of scientists? Consider the following:

  • The new version of CRISPR has recently been inserted into a modified viral delivery system and has been successfully used to repair a gene defect that causes Duchenne muscular dystrophy in mice by direct injection into the leg muscle or bloodstream, resulting in improved muscle condition throughout the body and even in the heart.
  • The leading scientific journal Science at the end of 2015 declared CRISPR “a breakthrough of the year”, standing above all other scientific discoveries for 2015.
  • On January 7, 2016, Dr. Church's company, Editas Medicine, filed an $ 100 million IPO, and the company has already received support from Google Ventures and the Bill and Melinda Gates Foundation.

In general, in my opinion, the CRISPR revolution is a turning point in science with staggering consequences. If everything works out, our world will never be the same. The prospects are just as impressive - to say the least - as with the advent of electric lighting, telephones, personal cars, airplanes, personal computers, the Internet and cell phones. Only this time we are talking not only about how you live, but also about whether you will live in general, and for how long: your health, longevity and their impact on the quality of your life.

Will it work? We will see. Opinions are different. Of course, there will be many problems, sudden turns and pits in our path. Even the famous scientist Craig Venter says that it will take 100 years to fix it. But George Church’s lab is already turning aging in experiments today. So the process looks very promising, incredibly fast and based on a solid scientific foundation of our knowledge of aging. I bet on Church, and almost everyone is of the same opinion. The end of at least some critical aspects of aging can be very near.

Life Extension Fundparticipates in this innovative and future-oriented project. The Life Extension Foundation helped Dr. Church by providing him with data from a research project on super-long-living. As Dr. Church notes in his interview, studying super-long-livers can give a new idea of ​​how to reverse a person’s aging when we get the right gene editing tools and apply them.

We hope that you will appreciate what, in our opinion, could be the coming revolution that will change your life.

Managing human aging through genome editing


Interview with George Church


Trying to delay aging is an outdated concept. A new goal is to convert it not only in animals, but also in humans. Rejuvenation is very important, as significant age-related disorders have already occurred in most people due to changes in gene expression profiles .

The gene expression profile changes with age . This affects the speed with which a person ages, and also determines what senile diseases he will have. But innovative gene editing techniques based on CRISPR's unique technology (clustered regular intermediate short palindromic repeats) are currently being successfully tested as age-related treatments for people.

In response to these breakthroughs, Life Extension magazine sent biogerontologist Dr. Gregory M. Faye to Harvard University for an interview with Dr. George Church , who is a leading developer of advanced CRISPR technologies. In it, Dr. Church explains the incredible possibilities of reversing human aging, which can reach their potential earlier than many expected.

The interview with Dr. Church begins with a discussion on the reversal of cell aging by restoring the expression of youth genes.

Fairies: If aging is caused by changes in gene expression, then the ability to control it using CRISPR technology can have huge consequences for human aging. Why do you think aging can be at least partially due to changes in gene expression?

Church: We know that there are cells that work worse with age, and that we have the opportunity to turn them into young cells again. This means that we can reset their biological clock to zero and keep them in this form for as long as we want. For example, we can take old skin cells that have a limited lifespan and turn them into stem cells (stem cells are cells that can turn into other types of cells) and then back into skin cells. This transformation leads to the fact that they look like cells of children's skin. It seems as if my 60 year old cells became the cells of a one year old baby. There are many markers associated with aging, and they all return to a young age.

Fairies: It is fantastic. Does this mean that reversing the aging of the skin on your face will allow you to rejuvenate your entire face?

Church : If you rejuvenate at the molecular level, this will not necessarily lead to external rejuvenation. So, for example, if I have a scar on my face, it does not have to disappear (although theoretically I do not exclude this). But we can change the tendency of your cells (and therefore your entire body) to decay over time.

Technology: how genes and their expression can be changed


Feiji : So CRISPR has allowed you to reverse the aging of human cells. CRISPR is a unique technology. The CRISPR molecular machine, consisting of a protein and some associated RNA, can now be made in the laboratory or in our own cells and can alter genes and their expression. This is an incredibly powerful method. Please tell us more about him.

Church : CRISPR is the latest method for editing the genome (editing the entire set of genes). Its advantage is that creating a specific CRISPR construct is much easier than other gene editing tools, and CRISPR is around 5times more accurate than other methods. The combination of ease of construction, high efficiency and great flexibility makes it the most powerful gene editing tool to date.

Feiji : Right now, with the help of CRISPR, you can change, delete, insert, activate and reduce the effect or completely turn off any gene with high accuracy - both temporarily and permanently. Now let's talk about what this new fantastic opportunity can bring.

Specific opportunities for reversing human aging TFAM: preserving eternal youth


Feiji : A lot of interesting things are happening in the study of aging these days. In 2013, the Sinclair Laboratory at Harvard made the news that the aging of mitochondria (which are energy producers within cells) is largely due to a decrease in the levels of one particular molecule in the cell nucleus: oxidized NAD (NAD +).

The team showed that they can reverse mitochondrial aging by simply giving nicotinamide mononucleotide (NMN) to old mice, which is a vitamin-like substance and can be converted to NAD +. This has led to a phenomenal overall rejuvenation, including the disappearance of signs of muscle atrophy, inflammation and insulin resistance. Now your laboratory has shown that there is a very interesting alternative in the form of genetic engineering, including TFAM (Transcription Factor A, Mitochondrial). Why is TFAM important and what have you done with it?

Church: TFAM is a key protein that regulates the production of NMN and NAD +. It allows cells to independently receive the NMN precursor, so you do not need to produce it outside the cell, and then try to deliver it from the outside. Ideally, you don’t want to take NMN for the rest of your life, you want to allow the body to create its own NMN and receive rejuvenation for at least several decades before you have to worry about NMN again. To achieve this at the cellular level, we used CRISPR to activate TFAM and made it semi-permanent.

Feiji : With this technology, you were able to increase the level of TFAM in the cell by 47time. This led to a restoration of ATP levels, an increase in NAD + and an increase in the NAD + / NADH ratio. She also increased the total mass of mitochondria and reversed several other age-related changes.

Church : Yes. We have several ways to measure mitochondrial function and their age-related changes. When we activated TFAM, mitochondrial function returned to what you would expect from a younger cell. We have embedded the ability to rejuvenate in the cell, allowed it to self-renew, and eliminated the need to take pills or injections.

GDF11: Towards General Rejuvenation


Feiji : Now let's move on to GDF11 (growth differentiation factor 11), which is a protein and a type of youth factor present in the blood of young organisms, but decreasing over time.

Church : Yes, my lab is affiliated with GDF11. We are collaborating with Amy Wagers, a Harvard biologist known for her work on heterochronous parabiosis, and her group, one of the first to deal with this problem.

Fairies: GDF11 has been reported to rejuvenate the heart, muscles and brain. It restores strength, muscle regeneration, memory, the formation of new brain cells, the formation of blood vessels in the brain, the ability to smell and function of mitochondria. All this is done with only one molecule. Infusion of young plasma containing GDF11 into old animals also has a good effect on other tissues, such as the liver and spinal cord, and improves the ability of old brain cells to form bonds with each other.

How would you use CRISPR to ensure that blood GDF11 levels never drop?

ChurchA: CRISPR-regulated GDF11 can be delivered in adulthood just when you need it. If you want to set it at a certain level, you can use the GDF11 sensor to provide feedback so that you can automatically control the production of GDF11. If necessary, you can recalibrate and fine-tune it, perhaps once every several decades with a different dose of CRISPR. This is a great molecule, and we work with it.

We have a number of other projects with Amy, we are engaged in muscle diseases, such as muscular dystrophy. We are working on possible treatments that include proteins such as myostatin and follistatin.

Strong bones and strong muscles


Feiji : Speaking of myostatin, the absence of which causes increased muscle development, you mentioned SENS 2014 in your conversation that you are interested in the possibility of improving muscles and bones. Is this another way to treat aging?

Church : Muscle atrophy and osteoporosis are symptoms of aging. The key to fighting them is eliminating the root causes, even if they are complex. Known genes involved in muscle atrophy, and genes that can reverse it. We are interested in such powerful tools as growth hormone, myostatin and the target for new drugs for the treatment of osteoporosis, RANKL (Kappa-B-ligand nuclear factor receptor activator).

Feiji : What about going beyond aging treatment and really improving people by making them stronger bones and stronger muscles?

Church: Instead of waiting for the muscles to atrophy and then trying to fix the problem or wait for someone to break the bone and put in a cast, we suggest making them stronger and stronger initially. Think of it as preventive medicine. We must be careful, but there are a lot of people around us who have much stronger bones and strong muscles, and we don’t see anything bad, so we know that such things are possible.

Feiji : Can osteoporosis be stopped?

Church : I would say that osteoporosis can definitely be reversed. The process of bone formation and its destruction is a regulated process that responds to conditions such as tension when standing or running. So yes, this is an example of what is reversible.

IKKβ: Reversing a Possible Whole Body Aging Program


Feiji : Let's move on to another manifestation of the aging process that is of great importance. According to an article published in Nature, body weight, body aging, and life expectancy are largely controlled by increased expression of one particular IKKβ protein in one particularly specific location, microglial cells in the hypothalamus in the brain. When this overexpression is prevented in mice, the average and maximum lifespan is increased by 20% and 23%, improves learning ability, improves physical activity, as well as skin thickness and bone density. In addition, collagen crosslinking is reduced, and gonadotropin production is increased. If these improvements could be combined with the improvements brought about by other interventions that we discussed, the consequences would be overwhelming.

Church : Yes. What you are talking about is the direction of a certain scientific school - aging, programmed by the neuroendocrine system, the brain. The reason mice die within two and a half years, and whales die after 160.

Fairies: Yes. And this is a particularly interesting problem, because it is not only important in itself, but also offers us practical ways to stop the changes that occur in the brain. This part of the brain is protected from most molecules placed in the bloodstream by the blood-brain barrier. Is it possible to use CRISPR technology through the blood-brain barrier and direct it to this biochemical pathway or other pathways in the brain?

Church : The blood-brain barrier is overrated, there are so many things that cross it, such as various drugs, viruses, and even whole cells. So, the answer is yes, we can deliver CRISPR through the blood-brain barrier.

Telomerase: brain aging and cancer?


Feiji : Telomerase is widely known as an enzyme that can prevent aging at the cellular level. But the lack of telomerase can also lead to aging of the brain and cancer. Can CRISPR be used to increase telomeres?

Church : Yes, it is certainly possible.

Gene expression profile is a measure of aging in humans.


Feiji : Could you explain the epigenetics and comment on the evidence that there is an epigenetic clock for aging?

Church : Epigenetics is all that controls gene expression. One of the components of epigenetics is DNA methylation, which is the addition of chemical objects called methyl groups to DNA in certain places. DNA methylation is important in part because it is an easy-to-measure component of an epigenome (the totality of all epigenetic states). It turns out that DNA methylation changes over time. In fact, the DNA methylation profile can predict a person’s age with an accuracy of about three years.

Basically, if you could change the biological age of a cell or organism to a younger one, and if these methylation sites (the total of which is called “methylomete”) really reflect biological age, then methylomete should change to a profile corresponding to an earlier age. In other words, if aging itself changes, then this aging biomarker must change in the same way. We use methylation sites as a measure of how well we have advanced in our research on the treatment of aging, and it works great.

DNA methylation is very useful for assessing a person’s age and can also be changed. Despite the fact that in normal life it is always associated with chronological age, in the world of reverse aging and epigenetic intervention, you can change it, and such a change will be significant.

Feiji : Not all 50-year-olds are biologically 50. Some are biologically older and some are biologically younger. People age at different speeds. All these differences can be detected in the state of methyloma. If methyl stands for a different age other than your chronological age, you are indeed older or younger than your chronological age, and this is confirmed by a number of other measurements.

Church: Yes everything is correct. Scientists who have discovered the epigenetic clock of aging have studied their variations and found interesting correlations with them. There are many ways to measure aging processes at the molecular level, and they tend to confirm each other. We do not know enough about the correlation between indicators such as methyl and aging factors, for example, GDF11, IKKβ and TFAM, but if you do something that reverses aging, then reverse changes should also be expected in methylome.

Fairies: Apparently, the DNA methylation model is becoming more chaotic with aging. For example, methylation models of identical twins begin to diverge over time, more altered profiles are associated with more pathology. This is consistent with a recent theory linking the absence of aging in some species (“negligible aging”) with a relatively stable model of gene expression over time, and ordinary aging with unstable and increasingly chaotic gene expression models. If you change gene expression back to what it should be, all this instability should be reversible, right?

Church: Right. The scatter of various parameters in any biological system increases when you move away from a physiologically normal state. You can think of the difference in methylation as another risk factor for aging and disease.

How to quickly detect and begin to correct the still unknown causes of aging at the genetic level



Feiji : If aging is caused by changes in gene expression, and these changes can be reversed, then we need to find all the important age-related changes in gene expression as soon as possible. How can this be done?

Church: The result of gene expression in the cell is the presence of specific RNAs and proteins, and they can be studied. You do not have to identify each individual RNA in a cell to determine changes in it, but you can, and we just developed a new method that allows us to see all tens of thousands of RNA in one cell at once, as well as in neighboring cells. So now we can see how different cells interact with each other. This new method, called in situ fluorescence sequencing or FISSEQ, allows all RNAs in a cell to be counted while simultaneously counting all RNAs in neighboring cells. In addition, we obtain three-dimensional coordinates for each RNA molecule in each cell.

Faye : This is incredible. How can you use this method to look for changes related to aging?

Church: Suppose that there are two different types of cells, and we want to know the expression of which genes distinguishes them from each other. We can first compare two cells using FISSEQ to determine differences in gene expression between them. Then we can select specific differences, which, in our opinion, lead to the fact that the cells will be different, and change the expression of specific genes in either of them or in both cells, using, for example, CRISPR, and see if we can transform one kind of cell in another. Even if we fail for the first time, we can make many assumptions about which RNAs are important, and how we can change them so that we succeed.

The same principle can be applied to any pair of cells. Comparing old cells with young ones, we can find out what makes an old cell old, and how to turn it into a young one.

Faye : Fantastic.

Church : One of the problems in studying the development and aging of the body is that it takes a lot of time. But if we know the epigenetic state of all these different cells, it does not matter what their age difference is, in just a few days you can reprogram the cell and reproduce the effects of decades of slow changes in the body or even reverse them. Therefore, in principle, we could turn a young cell into an old or old cell into a young one, because the only difference between them is epigenetics or gene expression.

Fairies: What other methods exist for identifying important gene targets that allow you to intervene in a person's aging process?

Church : There are four main ways to find key genes.

First, we can look at the genes that underlie individual variability in such things as low risk of viral infections, diabetes, osteoporosis, etc. The most extreme example here is to compare normal people with super-long-living, with those who live 110 years and more. In a small group or even in one person you can find unique useful genes.

There are hundreds of genes that have small effects, but then at the end of the Gaussian curve something like a double null mutant for myostatin or over / underproduction of human growth hormone appears. Genes that have tremendous influence and completely overlap the effects of small environmental and genetic factors are the right type of gene to look for.

The second way to find gene targets is to take them from basic research such as GDF11 and TFAM, which we talked about earlier.

The third way is to use a special genomic strategy, for example, mutating thousands of genes one after another, and see if any of them block aging, or using the FISSEQ method that we discussed earlier.

A fourth way to identify gene targets is to compare closely related species, one of which is aging much slower than the other (for example, naked mole rats and rats).

No matter where you get your results, you don’t have to worry about having too many hypotheses. Just use CRISPR to activate or inhibit this candidate gene and look for biomarkers of aging reversal that we talked about earlier. The idea is to see if your change influences or not, and whether it enhances other techniques that have been successfully tested in the past.

Feiji : So, if we saw something unusual in super-long-livers, we could create the same change, for example, in the normal line of human cells and see if the correct longevity pattern appeared.

Church: Yes.

Faye : I was told by James Clement, funded by the Life Extension Foundation, that they were working with you on super-long-genetics, you could even take their gene expression models, put them in mice and see if the mice grow older more slowly.

Church: Right. Our protocol is likely to collect results from four different sources and first test them on human cells. Working directly with human cells, we will not spend many years on mice, which is quite expensive, only to find out that the reception does not work in humans. We can do a cheaper and more relevant study on human cells, confirm it on mice, then test on larger animals, and then in humans. I think that the transition from human cells to mice and back to people is likely to save us time and money. Many blood cell testing systems are getting better and better, such as “organs on a chip” or organoids that are becoming more and more attractive in in vivo studies.

Intervention for Aging Intervention


Feiji : Can the high specificity of CRISPR eliminate the side effects of some anti-aging interventions? For example, I am working on regenerating the thymus in humans and restoring T-cell production using growth hormone. Although growth hormone does not cause cancer in adult animals or humans, it slows down DNA repair in animals - an effect not related to its beneficial effect on thymus regeneration.

Church : So you want to get rid of its effect on DNA repair, while maintaining good effects.

Faye : Yes. If CRISPR can be used to act directly on genes of interest and not follow the usual biochemical pathways, we could avoid unwanted effects, right?

Church: Exactly. You can make a list of all growth hormone targets and either select the targets that you need and activate them selectively, or select the targets that you don't need and block them so you can use growth hormone as usual, but without inhibiting DNA repair .

Feasibility of using CRISPR in an adult body


Feiji : To reverse the aging process of people, CRISPR technology must ultimately be applied throughout the body, not just in vitro cells. How appropriate is CRISPR technology in a living organism?

Church : Gene therapy can be based on ex vivo manipulations, in which cells are removed from the body, genetically modified, and then returned to the body or in vivo (within the body) methods, in which, for example, a modified virus can be used to transfer the gene cassette into different cells of the body. Each of these methods has pros and cons.

There are viral and non-viral systems that can be used to deliver CRISPR constructs; they will leave the blood vessels and enter the tissues. The delivery system may contain CRISPR, directing RNA and donor DNA, or it may contain CRISPR, directing RNA and protein activator, and so on. But regardless of whether it is viral or non-viral, the total mass of constructs for editing the genes to be delivered must be significant. But this is not a problem, you can not rush and deliver them in batches.

Fortunately, there are cheap ways to produce biological products. The price of wood, and even food and fuel, is roughly in the range of the dollar per kilogram. If we could make a kilogram of the viral delivery system and load it using CRISPR, then it could become inexpensive enough to apply it to the whole body.

Feiji : Yes, a kilogram would be enough! Thus, the viral delivery system contains a gene for CRISPR, a separate gene for directing RNA, and so on. When it delivers these genes to a cell, it produces proteins and nucleic acids, and all the components just assemble in it, right?

Church : Yes.

Feiji : Which CRISPR delivery system is the best?

Church: Adeno-associated viruses (AAVs) are one of the best delivery systems these days because they can target tissues other than the liver (where many other delivery systems end up on their way). This is an active area of ​​research. It is booming, and the CRISPR revolution has made it even more attractive.

Security


Feiji : How specific can a virus be designed to deliver CRISPR to only one type of body cell?

Church : For every thousand cells of a certain type, usually there is one wrong delivery to a cell of another type that was not the target. This is pretty good. In addition, if you have something that is needed for all cells, it must be delivered to all cells. Even if you have something specific, it usually doesn't matter which cells it is delivered to. But in cases where this is important, you can get the correct delivery about 999 times out of 1000.

Fey : Can there be problems with one wrong delivery out of 1000? In general, it would still have been a lot of mistakes.

Church: You need to remember that most drugs actually get into all the cells of your body. It would be superfluous to say that CRISPR should be more specific than any previous drug.

Safety also depends on which brand of “explosives” you are dealing with. Like nitroglycerin or TNT. If you make safety one of your top priorities, you will not use the technique if it may not work properly until you are sure of very high cellular specificity.

Faye : It’s also very important for the safe use of CRISPR - it’s not only what cell it got into, but whether it is editing the correct gene. How accurately can CRISPR be targeted in the genome?

Church: In practice, when we introduced our first CRISPR in 2013, its error rate was about 5%. In other words, CRISPR would incorrectly edit 5 cells out of 100. Now we get about one error per 6 trillion cells.

Feiji : This means that the probability of a serious mistake is now so low that it is very difficult to measure, it is much less than the speed of spontaneous mutations.

Church : Yes. And besides this, you can use small molecules as conditional activators to ensure that the proposed changes occur only in the right cells. The combination of a fully safe small molecule activator and programmed targeting is unprecedented.

Other checks may also be introduced for even greater security. For example, when a virus enters a cell, it can make further decisions. He can essentially ask, “Am I in the right place?” - before acting. There is a whole field of molecular logic that can be used to avoid errors.

Availability


Feiji : Will aging treatment be affordable with this approach?

Church : If you look at the current price, it looks huge and inaccessible. About 2,000 gene therapies are involved in clinical trials, but the only one approved for use costs more than $ 1 million per dose. You need only one dose, but at this price it is clearly not available to most people. As far as I know, this is the most expensive medicine in history.

Feiji : What is this medicine?

Church: It is called Glybera. It treats pancreatitis, a rare genetic disease. But the first sequencing of the human genome cost $ 3 billion per genome, and now its price is only $ 1,000, so I think that reducing the price from one million to thousands will not be a problem.

Feiji : Another cost saving for interfering with the aging process would be if we could significantly slow down aging by simply changing 5-10 genes. This could lead to the fact that the total cost is reduced to acceptable.

Church : Right. The combination needed to change, say, a trillion cells throughout the body and 10,000 genes would be complex. But if you could change only part of the cells and genes, then you would make it more accessible.

Fairies: You said CRISPR therapy has the potential to replace conventional drugs. Why?

Church : The great advantage of CRISPR is that it is much better than the usual procedures, it has excellent capabilities for “placing control buttons” where there are currently no buttons. Now you need to be very lucky to get a good drug that will do exactly what you want, and nothing else. With CRISPR we can be much more accurate.

How much can be fixed at one time?


Feiji : If we know what to do, and we can afford to do it, how quickly can we reverse aging? What about the simultaneous modification of, say, 10 different types of cells in the body that cause most senile changes? Can they all be changed at the same time?

Church: “Everything” is a big word, but I think a lot can be changed right away. This can be done with what we call multiplexing, using a mixture of viruses or delivery vectors that allows you to make many changes at a time. But you can go the slow way, starting with the highest priority fabrics, and then go to the lower priority ones. Determining which tissues are top priority may vary depending on the patient’s heredity, it is possible that a particular tissue will be at a higher risk of aging.

The road to the clinic: how long does it take?


Feiji : Using your best method, how long will it take for a human test to be possible?

Church : I think this can happen very quickly. It may take years to get full approval for use, but it may take only a year to get permission to test the first phase. Tests of GDF11, myostatin and others have already been conducted in animals, as well as a large number of CRISPR studies. I think that in a year or two we will see the first human trials.

Feiji : Can you tell me what these trials might be?

Church: I helped create a company called Editas that deals with CRISPR-based genome treatments. Some of them are aimed at rare childhood diseases, while others, I hope, will be aimed at aging. We also have a company specializing in the treatment of aging that will test these treatments on animals and humans.

Aging Treatment, FDA and Dietary Supplement Model


Feiji : Is it a problem that the FDA does not recognize aging as a disease?

Church : The FDA deals with many of the symptoms of aging, such as osteoporosis, muscle dystrophy, heart disease, cognitive dysfunction, etc. It is generally more difficult to prove a preventive approach than the effectiveness of a medication that treats a quick and very dangerous disease. And since the FDA does not want you to make any unreasonable statements about your health, they should take responsibility for the regulation of any health-related condition that could be reported. In fact, aging does not have to be officially a disease.

Feiji : It was suggested that the FDA simply evaluate safety rather than effectiveness. What do you think about it?

Church: I love it. The Internet is likely to save us from ineffective drugs. The nutritional supplement market is an excellent example of the fact that safety is all that is needed to resolve. You can supply a nutritional supplement to the market only on the basis of its safety, but you cannot supply a prescription drug only on the basis of its safety. There should be a general rule.

Feiji : Freedom of innovation and the creation of nutritional supplements is what the Life Extension Fund is. They fund all my cryobiology research, and their nutritional supplements are based on scientific research. Good consequences of freedom and free work.

Church: It's true. I'm just saying that the FDA has a double standard. The standards for nutritional supplements differ from the standards for new prescription drugs.

Faye : Perhaps if it were to change the standards for supplements, we would have much more drugs, and everything would be much better.

Church : Yes. Focusing on security is probably the right model.

Feiji : Thank you, doctor, for an amazing excursion into the near future!

About Authors


George M. Church, PhD - American geneticist, molecular engineer and chemist. Professor at Harvard Medical School and Professor of Health Sciences at Harvard and MIT. He founded the Wyss Institute for Biologically Inspired Engineering and 9 bioengineering companies.

Gregory M. Fahy, PhD - Cryobiologist and Biogerologist, Vice President and Principal Researcher at Twenty-First Century Medicine, Inc. The world's best expert on cryopreservation and vitrification of organs.

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