The Undoing Aging conference, a collaboration between the SENS Research Foundation and Michael Greve’s Forever Healthy Foundation, took place on March 15-17 in Berlin, and it saw many researchers, advocates, investors, and other important members of the longevity community gather together to learn about the latest progress in rejuvenation biotechnology.

LEAF arranged a travel grant for Anna Dobryukha, one of the best Russian journalists writing about aging, longevity, and rejuvenation research, to join us, so it made sense to collaborate with her on the most interesting interviews. Anna works for Komsomolskaya Pravda, one of the largest Russian publishing houses, which has a newspaper, a radio station, and a website with over 40 million readers. Anna has also published an article based on this and other interviews taken during the conference which you can find here.

During the conference, we had the opportunity to interview Dr. Jonathan Clark, who has recently been focusing on skin aging and the interactions of collagen in this process. He is the head of the biological chemistry department at the Babraham Institute, where his group carries out aging research. Dr. Clark has some interesting research which he presented at the conference but which has yet to be published, this means that he could not tell us everything he had discovered in this interview, but don’t worry, we have agreed a follow-up interview with him once his data is published.

Present during the interview were Anna (A), Elena Milova (E), Steve Hill (S), the interview has been edited for clarity and language.







A: What are the benefits of breaking the crosslinks?

J: In the literature, what they will tell you is that the tissue should become more supple and it shouldn’t be as stiff. It should be a good thing; this is what you would expect from the literature.E: Let’s hypothesize that we have a therapy that could remove the crosslinks that we don’t really need.

J: The question is whether the crosslinks really cause tissue stiffness and wrinkles. A lot of people would say it does, but I would question what the evidence might actually be of that, because there is a tendency in the literature to assume that if you see something increasing, then that must be the cause of the stiffness. Actually, there may be another mechanism, and that’s what our research is trying to show: how collagen really functions and what the impact of crosslinking really is. Because nobody has really explained before in the literature how collagen functions, what is actually going on. People are assuming it’s a very static material; actually, it’s a very dynamic material. We are trying to show that those properties are actually being changed. My research swims against the flow of accepted, normal hypotheses. I am showing that the things that people believe are not necessarily correct. This is why I’m finding this so difficult because I want to actually tell you what I’ve found.

E: This is a really important part of the work of a scientist, I believe. Because changing is painful, and there are some people who are not really able to change their minds, their opinions of different phenomena. So, it is nice. We are looking forward to the publication of your study. Could you please tell us what would be your advice to an ordinary person, who would like to kind of try to avoid excessive crosslinks in their bodies and problems related to crosslinking, starting from diets and different aspects of lifestyle. Do you think that, in general, having a healthy lifestyle would help to slow down the processes of aging, particularly the process of crosslinking?

J: Personally, I certainly believe it does. I think that there’d be a message that would be good for everybody; I think that on a number of levels, if you live a healthy lifestyle, and you exercise and eat well, sensibly, you will do yourself lots of good.







E: Could you please explain to our readers how physical activity could interact with the process of crosslinking and slow it down?

J: Can I do some more work before I go to print with that?

E: That’s a real scientist.

J: I have a gut feeling but I don’t want to express it.

E: Ok. Maybe we’ll rephrase it. As a representative of this field, you know quite a lot about aging and how it can hurt the body. So, probably, you know the best ways of how to keep yourself healthy? So, for instance, what do you do to remain healthy for as long as possible?







J: It’s known that exercise boosts collagen synthesis. There are papers out there where the turnover of collagen has been measured in athletes in their tendons, and it’s been shown to increase. It directly responds to exercise, and I think that is a good thing. I try and eat well; at least my wife makes me eat well. She watches my diet very carefully and tells me that I need to do better, but I put a lot of effort into exercise. For me personally, around 40, I certainly found I had to start doing a lot more exercise. If nothing else, it reduces the feeling of stiffness and aches and pains that you get first thing in the morning. So for a long, while now, when I get up in the morning, I do at least half an hour of yoga. I will go and exercise in a gym at least twice a week, and I go climbing three times a week. I realize that’s a lot for most people.

A: You mean, climbing a wall?

J: Yeah, rock climbing. I am actually in the process of building a climbing gym at home because I want to be able to get there more easily and not have the travel time of going to the gym. I think it is important, and so I am personally investing in making sure that I, my wife, and the rest of my family can exercise well and easily. If you are spending an hour getting to the gym and an hour getting back, that’s a large chunk of your evening.

E: You have probably heard about the initiatives of biohacking and self-experimenting, which are quite common for the community of life extensionists. Do you use some additional ways, such as drugs, pills, or supplements, that you believe are good to slow down the processes of aging?

J: I believe that generally, if you have a good diet, and you understand what you are eating, then you can provide everything your need in your diet. If I’m feeling run down, I might take vitamin C tablets; I don’t know if they really make any difference or not, but I feel that they might.







A: What do you mean by a good diet? Does it include meat or is it a vegetarian diet? What do you mean?

J: I generally eat relatively small amounts of chicken and fish. Sometimes, no meat; a lot of vegetables. We eat very little red meat. It was quite a shock coming here to Berlin. Actually, the other night, when we went to that pub, I didn’t realize they didn’t serve up vegetables; there was just a huge chunk of meat. I couldn’t believe that. That was quite difficult. We very rarely eat things with a lot of sugar; puddings, cakes, things like that; just don’t eat them. If I want to cruise on stuff, I eat nuts and fruit.

E: We know that glucose from different sweet products and carbs can actually add to these processes of crosslinking, but what do we know about fructose from fruit?

J: Very little. It probably does the same. It is supposed to be more reactive. I think it depends on exposure. The thing is, once glucose has reacted with the lysines on the proteins, there is a whole series of chemical changes that occur. At that point, there is probably very little difference between glucose and fructose. Initially, fructose will react faster; that’s what you would expect. Whether that’s a problem in the equation, at the moment, we don’t know.

S: Exercise has been known to stimulate interleukin-7, which promotes growth. Do you think it plays a role in the connection between exercise and skin aging?







J: I don’t have an answer to that. It is not something that I’ve looked at. I am working on the basis that if you want to replace old collagen with young collagen, then exercise may be a mechanism for doing that. If athletes are getting a high turnover when they do exercise, then you can expect it to happen in average people if they are doing a lot of exercise too. How much exercise you need to do to stimulate that turnover, we don’t know.

S: So, do you think a possible solution to this problem of skin aging may be to boost, in some way, the level of collagen production?

J: I don’t know the answer to that.

S: Collagen production drops as you age, right?

J: It definitely does drop, but I am trying to remember how much it drops by.







S: I think in terms of potentially combating things like sarcopenia, for example. A therapy that encourages collagen production can help arterial stiffness and hypertension, which is something that most people get.

J: Blood vessels are interesting.

S: They are different, aren’t they?

J: They are different. The turnover of blood vessels, certainly aortic tissue, seems to be very similar to the turnover of skin.

S: The mechanisms are similar, right? The collagen acts in a similar way?J: Skin turnover would be expected to drop from about one percent a day down to just under half a percent a day when you age. This is a big difference, though, so if you could increase the turnover, the deposition of collagen in skin, and turn it back to one percent a day, that would be quite a good thing to do.







S: The skin would become more plump because there would be more of these feather-like structures within the tissue. So, when can you deliver?

J: (laughs) I don’t know.

S: From a practicality point of view, we’re obviously quite a long way away from translating this sort of thing to people, but you’ve mentioned that you’re moving to human skin next?

J: I’m hoping to move to human tissue.

S: Do you think because the skin’s a lot easier to access than internal organs, it will be considerably easier to prove what works and what doesn’t?







J: Skin’s quite an interesting tissue to biopsy because it seems to correlate quite well to tendons in terms of crosslinks so far.

E: I wanted to ask a question regarding your plans for the near future. Your research plans maybe?

J: Our research plans are to take the research that we have done on tendons and apply it to arterial tissue, particularly the aorta, because the aorta stiffens with age. If we can understand what is happening in the aorta, it opens up the potential to modify aortic tissue and make it less stiff and less of a problem.

E: So that is technically the road to prevent or cure some heart diseases?

J: Blood pressure would be a particular disease state, but obviously high blood pressure then leads to other issues.







E: Not long ago, I interviewed a Russian specialist who is working in aesthetic medicine. His name is Vadim Zorin, and he is working in a Russian research institution called the Human Stem Cell Institute. Their project is the multiplication and injection of fibroblasts, autological fibroblasts, back into the patient’s skin in order to restore its elasticity. Because it turns out that the number of fibroblasts of the skin, specifically active fibroblasts, drops with age significantly, and that means that less collagen and elastin are produced. So they see this as a solution. Do you think it might work well?

J: Sounds like it could. Sounds like a reasonable approach. But, how many fibroblasts can you culture; how are you going to get them to go into the right place and spread them around? Presumably, you don’t want one half of your face to be young and the other to be old. We need a nice, even distribution. But those are technical problems; I’m sure they’ll be solved.

E: I think that is it.

We would like to thank Dr. Clark for taking the time to speak with us and we look forward to catching up with him soon when he has published the data he has been researching about skin aging. LEAF will be bringing you a follow-up interview with Dr. Clark once this data is published that potentially sheds new light on how skin aging happens.





