Harvard is reversing aging

Interview with George Church

Human Age Reversal at Harvard University (Gregory M. Fahy, PhD, Life Extension).

Translated by Ariel VA Feinerman, Geektimes

Is the End of Aging near (foreword by Gregory Fahey)

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

Why? For three very simple reasons. 

Firstly, as Dr. Church emphasized in his lecture, aging seems to be largely controlled by the action of a small subset of your genes and, mainly, by master genes controlling 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's becoming increasingly clear that genes also determine how you age, and perhaps whether you age 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 a test tube, but also in the whole body, and even in the brain. 

Dr. Church's attention is focused on the CRISPR method (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 in order 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 beginning to approach the control of aging 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 did not have the desire to use it in real medicine. Fortunately, Dr. Church wants his achievements to quickly end up in clinics. He intends to make the control of aging 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 that his laboratory had already reversed aging in mice, and human trials could take place in a few years. Dr. Church stated: 

"One of our biggest economic disasters right now is our aging population."

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

He said he saw: 

"A scenario [in which] everyone receives gene therapy, not only for the treatment of rare diseases such as cystic fibrosis, but diseases that everyone has, including aging."

Dr. Church also mentioned his personal interest in the treatment of human aging when he stated: 

"I want to get younger, I'm trying to do something new every few years anyway."

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

CRISPR is a technology that originally originated 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 are able to adjust or "edit" DNA, they will begin work on restoring youth in the elderly. 

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

A new version of CRISPR was recently inserted into a modified viral delivery system and successfully used to correct a gene defect that causes Duchenne muscular dystrophy in mice by direct injection into the leg muscle or into the bloodstream, which led to an improvement in the condition of muscles throughout the body and even in the heart.

Leading scientific journal Science at the end of 2015 declared CRISPR the "breakthrough of the year", standing above all other scientific discoveries for 2015.

On January 7, 2016, Dr. Church's company, Editas Medicine, filed documents for an IPO worth $100 million, and the company has already received the support of Google Ventures and the Bill and Melinda Gates Foundation.

In general, in my opinion, the CRISPR revolution is a turning point in science with stunning consequences. If everything works out, our world will never be the same. The prospects are 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 it's not just about how you live, but also about whether you will live at all, and for how long: your health, longevity and their impact on the quality of your life. 

Will it work? We'll see. Opinions change. Of course, there will be a lot of problems, sudden turns and holes on our way. Even renowned scientist Craig Venter says it will take 100 years to fix everything. But George Church's laboratory is already turning aging into experiments today. So the process looks very promising, incredibly fast and based on a solid scientific foundation of our knowledge about aging. I'm betting on Church, and almost everyone has a similar opinion. The end of at least some critical aspects of aging may be very close. 

The Life Extension Foundation participates in this innovative and future-oriented project. The Life Extension Foundation assisted Dr. Church by providing him with data from a scientific project dedicated to super-long-livers. As Dr. Church notes in his interview, the study of super-long-livers can give a new idea of how to reverse human aging when we get the right gene editing tools and apply them. 

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

Managing human aging with genome editing

Trying to delay aging is already an outdated concept. The new goal is to convert it not only in animals, but also in humans. Rejuvenation is very important, since 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 rate at which a person ages, and also determines which senile diseases he will have. But innovative gene editing techniques based on the unique CRISPR technology (clustered regular intermediate short palindromic repeats) are currently being successfully tested as an age-related therapy for humans. 

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

The interview with Dr. Church begins with a discussion of the issue of reversing cell aging by restoring the expression of "youth genes". 

Faye: 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, in your opinion, can aging be at least partially caused by changes in gene expression? 

Church: We know that there are cells that work worse with age, and that we have the ability to turn them back into young cells. 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 baby skin cells. It's as if my 60-year-old cells have become the cells of a one-year-old child. There are many markers associated with aging, and they all return to a young age. 

FAYE: It's fantastic. Does this mean that reversing the aging of the skin on your face will allow you to rejuvenate the whole face? 

Church: If you rejuvenate at the molecular level, it 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 whole body) to decay over time. 

Technology: how genes and their expression can be changed

Faye: So CRISPR 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 newest method for genome editing (editing the entire set of genes). Its advantage is that it is much easier to create a specific CRISPR construct than other gene editing tools, and CRISPR is about 5 times 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. 

Faye: Right now, with CRISPR, you can modify, delete, insert, activate and reduce the influence or completely turn off any gene with high accuracy – both temporarily and permanently. Now let's talk about what this fantastic new opportunity can bring. 

Specific opportunities to reverse human aging 

TFAM: preserving eternal youth

Faye: There are a lot of very interesting things going on in the study of aging nowadays. In 2013, the Sinclair laboratory at Harvard made the news that the aging of mitochondria (which are energy producers inside 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 old mice nicotinamide mononucleotide (NMN), which is a vitamin-like substance and can be converted to NAD+, for one week. This led to phenomenal overall rejuvenation, including the disappearance of signs of muscle atrophy, inflammation and insulin resistance. Now your lab 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 regulating the production of NMN and NAD+. It allows cells to independently obtain the NMN precursor, so you don't 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 let the body create its own NMN and get rejuvenated for at least a few 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. 

Faye: With this technology, you were able to increase the TFAM level in the cell by 47 times. This led to a recovery in ATP levels, an increase in NAD+, and an increase in the NAD+/NADH ratio. It 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 functions returned to what you would expect from a younger cell. We have built the ability to rejuvenate into the cell, allowed it to self-renew and eliminated the need to take pills or injections. 

GDF11: on the way to general rejuvenation

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

Church: Yes, my lab is connected to 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 tackle this problem.

Faye: GDF11 is 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 the function of mitochondria. All this is done by just 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 connections with each other. 

How would you use CRISPR to make sure that the level of GDF11 in the blood never decreases? 

Church: CRISPR-regulated GDF11 can be delivered in adulthood, exactly when it is needed. 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 GDF11 production. If necessary, it can be recalibrated and fine-tuned, perhaps once every few decades with a different dose of CRISPR. It's a great molecule, and we're working with it. 

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

Strong bones and strong muscles

Faye: Speaking about myostatin, the absence of which causes increased muscle development, you mentioned in your SENS 2014 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 dealing with them is to eliminate the underlying causes, even if they are complex. There are known genes involved in muscle atrophy and genes that can reverse it. We are interested in such powerful agents as growth hormone, myostatin and a target for new drugs for the treatment of osteoporosis, RANKL (activator of the kappa-B-ligand nuclear factor receptor). 

Faye: How about going beyond the treatment of aging 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 waiting for someone to break a bone and put a cast on, we suggest making them stronger and stronger initially. Think of it as preventive medicine. We need to 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 wrong, so we know that such things are possible. 

Faye: Is it possible to stop osteoporosis? 

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

IKKß: reversal of a possible whole-body aging program

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

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 why mice die within two and a half years, and whales after 160. 

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

Church: The blood-brain barrier is greatly overestimated, there are a lot of things that cross it, for example, various drugs, viruses and even whole cells. So, the answer is yes, we can deliver CRISPR across the blood-brain barrier. 

Telomerase: brain aging and cancer?

Faye: Telomerase is widely known as an enzyme that can prevent aging at the cellular level. But the absence of telomerase can also lead to brain aging and cancer. Is it possible to use CRISPR to increase telomeres? 

CHURCH: Yes, it is certainly possible. 

Gene expression profile is a measure of aging in humans

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

Church: Epigenetics is everything that controls gene expression. One of the components of epigenetics is DNA methylation, which consists in adding 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 the 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 the "methylome") really reflect the biological age, then the methylome should change to a profile corresponding to an earlier age. In other words, if aging itself changes, then this biomarker of aging should change in the same way. We use methylation sites as a measure of how well we have progressed in our research on the reversal of aging, and it works perfectly. 

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

Faye: Not all 50-year-olds are biologically 50. Some of them are biologically older and some are biologically younger. People age at different rates. All these differences can be detected in the state of the methylome. If the methylome indicates a different age 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, that's right. Scientists who discovered the epigenetic clock of aging 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 don't know enough about the correlation between indicators such as methylome and aging factors, for example, GDF11, IKKß and TFAM, but if you do something that reverses aging, then the reverse changes should also be expected in the methylome. 

Faye: Apparently, the DNA methylation model becomes more chaotic as we age. For example, the methylation patterns of identical twins begin to diverge over time, more altered profiles are associated with greater 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 normal aging with unstable and increasingly chaotic models of gene expression. If you change the gene expression back to what it should be, all this instability should be reversible, right? 

CHURCH: That's right. The spread of various parameters in any biological system increases when you move away from a physiologically normal state. You can think of the methylation difference as another risk factor for aging and disease. 

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

Faye: 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 a cell is the presence of specific RNAs and proteins, and they can be studied. You don't have to identify every single 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 RNAs 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 fluorescent sequencing or FISSEQ, allows you to count all the RNAs in a cell while simultaneously counting all the RNAs in neighboring cells. In addition, we get three-dimensional coordinates for each RNA molecule in each cell. 

Faye: It's unbelievable. How can you use this method to find changes related to aging? 

Church: Suppose there are two different types of cells, and we want to know which gene expression distinguishes them from each other. We can first compare two cells using FISSEQ to determine the differences in gene expression between them. Then we can select the specific differences that we think lead to the cells being 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 turn one kind of cell into another. Even if we don't succeed the first time, we can make a lot of 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. By 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 long time. But if we know the epigenetic state of all these different cells, then no matter what their age difference is, in just a few days it is possible to reprogram a 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 one or an old cell into a young one, because the only difference between them is epigenetics or gene expression. 

Faye: What other ways are there to identify important gene targets that can interfere with the aging process of a person? 

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

First, we can look at the genes underlying individual variability in things like low risk of viral infections, diabetes, osteoporosis, etc. The most extreme example here is to compare normal people with super–long-livers, with those who live 110 years or 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 zero mutant for myostatin or over/under-production of human growth hormone appears. Genes that have a huge impact and completely override the effects of small environmental and genetic factors – this is 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 by one, and see if any of them blocks aging, or using the FISSEQ method, which we discussed earlier. 

The fourth way to determine gene targets is to compare closely related species, one of which ages much slower than the other (for example, naked diggers 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 the aging reversal that we talked about earlier. The idea is to see if your change affects or not, and whether it reinforces other techniques that have been successfully tested in the past. 

Faye: So, if we saw something unusual in super-long-livers, we could create the same change, for example, in a normal human cell line and observe whether the correct longevity pattern has appeared. 

CHURCH: Yes. 

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

CHURCH: That's right. Our protocol will probably collect results from four different sources and test them on human cells first. Working directly with human cells, we won't spend many years on mice, which is quite expensive, only to find out that the technique doesn't work on humans. We can do a cheaper and more relevant study on human cells, confirm it in mice, then test it on larger animals, and then in humans. I think that the transition from human cells to mice and back to humans will most likely save us time and money. Many blood cell testing systems are getting better and better, such as "organs on a chip" or organoids, which are becoming more and more attractive in in vivo research. 

Elimination of problems with aging intervention

Faye: Can the high specificity of CRISPR eliminate the side effects of some anti-aging interventions? For example, I am working on the regeneration of the thymus in humans and the restoration of 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 unrelated to its beneficial effect on thymus regeneration. 

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

FAYE: Yes. If CRISPR can be used to directly affect the 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 the 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 that you can use growth hormone as usual, but without inhibiting DNA repair.

The feasibility of using CRISPR in an adult body

Faye: To reverse the aging process of humans, CRISPR technology eventually needs to be applied throughout the body, not just in cells in a test tube. How appropriate is it to use 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 on in vivo (inside the body) methods, in which, for example, a modified virus can be used to transfer a gene cassette to 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, guide RNA and donor DNA, or it may contain CRISPR, guide RNA and protein activator, and so on. But regardless of whether it is viral or non-viral, the total mass of gene editing constructs that need to be delivered should be significant. But this is not a problem, you can take your time and deliver them in batches. 

Fortunately, there are cheap ways to produce biological drugs. The price of wood and even food and fuel is approximately in the range of a dollar per kilogram. If we could make a kilogram of a viral delivery system and load it with CRISPR, then it could become inexpensive enough to apply it to an entire organism. 

Faye: Yes, a kilogram would be enough! So the viral delivery system contains a gene for CRISPR, a separate gene for guide RNA, etc. When it delivers these genes to a cell, it produces proteins and nucleic acids, and all the components just assemble themselves in it, right? 

CHURCH: Yes. 

Faye: Which CRISPR delivery system is the best? 

Church: Adeno-associated viruses (AAV) are one of the best delivery systems nowadays because they can be targeted at tissues other than the liver (where many other delivery systems end up). This is an active area of research. It is booming, and the CRISPR revolution has made it even more attractive. 

Safety

Faye: 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, there is usually one incorrect delivery to a cell of another type that was not a target. This is quite good. Also, if you have something needed for all cells, it should 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 it is important, you can get the correct delivery about 999 times out of 1000. 

Faye: Can there be problems with one incorrect delivery out of 1000? In general, it would still turn out to be a lot of mistakes. 

Church: You have to remember that most drugs actually get into all the cells of your body. It would be a double standard 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 a technique if it may not work properly until you are sure of a 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 also whether it edits the right 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. 

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

CHURCH: Yes. And in addition, small molecules can be used as conditional activators to ensure that the intended changes occur only in the right cells. The combination of a completely safe small molecule activator and programmable targeting is unprecedented. 

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

Availability

Faye: Will it be affordable to reverse aging with this approach? 

Church: If you look at the current price, it looks huge and unaffordable. About 2,000 gene therapies are involved in clinical trials, but the only one approved for use costs more than one million dollars per dose. You only need 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. 

Faye: What kind of medicine is this? 

Church: It's 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. 

Faye: Another cost savings for intervening in the aging process would arise if we could significantly slow down aging by simply changing 5-10 genes. This could lead to the fact that the total cost will decrease to an acceptable one. 

CHURCH: That's right. The combination needed to change, say, a trillion cells in the whole body and 10,000 genes would be difficult. But if you could change only a part of cells and genes, then you would make it more accessible. 

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

Church: The big advantage of CRISPR is that it is much better than conventional procedures, it has excellent opportunities to "place 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?

Faye: If we know what to do and we can afford to do it, how quickly can we reverse aging? How about simultaneous modification of, say, 10 different cell types 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 vectors for delivery, allowing many changes to be made at a time. But you can also go the slow way, starting with the highest priority fabrics, and then move on to the lower priority ones. Determining which tissues are the highest priority may vary depending on the patient's heredity, it is possible that a particular tissue will be at higher risk of aging. 

The road to the clinics: how long will it take?

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

Church: I think it can happen very quickly. It may take years to get a full application permit, but it may take as little as a year to get a permit for phase one testing. Tests of GDF11, myostatin and others have already been conducted on 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. 

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

Church: I helped create a company called Editas, which deals with CRISPR-based genome therapies. Some of them are aimed at rare childhood diseases, and 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, the FDA and the Dietary Supplement Model

Faye: Is it a problem that the FDA doesn't recognize aging as a disease? 

Church: The FDA deals with many symptoms of aging, such as osteoporosis, muscular dystrophy, heart disease, cognitive dysfunction, etc. As a rule, it is more difficult to prove a preventive approach than the effectiveness of a drug that treats a rapid and very dangerous disease. And since the FDA doesn't want you to make any unsubstantiated claims about your health, they should have taken responsibility for regulating any health-related condition that could be claimed. In fact, aging does not have to officially be a disease. 

Fahey: It has been suggested that the FDA simply assesses safety, not efficacy. How do you feel about this? 

Church: I really like it. The Internet will probably rid us of ineffective medicines. The food additives market is a perfect example of the fact that safety is all that is necessary for resolution. You can supply a dietary 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. 

Faye: Freedom of innovation and the creation of dietary supplements – that's what the Life Extension Fund is. They fund all my research in the field of cryobiology, and their dietary supplements are based on scientific research. Good consequences of freedom and free work. 

CHURCH: It's true. I'm just saying that there is a double standard in the FDA. The standards for dietary supplements differ from the standards for new prescription drugs. 

Faye: Maybe if this had been changed in favor of supplement standards, we would have had a lot more drugs, and everything would have been much better. 

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

Faye: Thank you, Doctor, for an amazing excursion into the near future! 

About the authors:
George Church, PhD is an American geneticist, molecular engineer and chemist. Professor at Harvard Medical School and Professor of Health Sciences at Harvard and MIT. Founded the Wyss Institute for Biologically Inspired Engineering and 9 bioengineering companies. 
Gregory M. Fahy, PhD – Cryobiologist and Biogerologist, Vice President and Chief Scientist at Twenty-First Century Medicine, Inc. The world's best expert on cryopreservation and vitrification of organs.

Portal "Eternal youth" http://vechnayamolodost.ru  24.07.2017