Covid exacerbates cellular senescence – geneticist

SS: We're going to talk about NAD a lot, a little later. But look, there's this idea that elderly people are more vulnerable to Covid, because their immune systems are weaker, as well. But we also know that some people's immune systems, young people react to the virus so vigorously that they start to cause damage to their hosts. And then in order to treat that infection, I mean, your immune systems have to be weakened. Does that mean that the weaker immune systems in older people may actually be helpful in Covid treatments? How does it work?

DS: Yeah, well, immunology is an extremely complicated field. That's one of the reasons, you know, I prefer to work on muscle, it's just simpler, because you need different types of immune reactions depending on the type of infection and the phase of the infection. And so early on, you want to have a really robust attack on the virus, which young people generally are good at. But then you don't want it to go too crazy or too aggressive and you need to be able to shut that down again once the virus starts to go away. Instead, what seems to happen in the elderly is they don't have a strong initial response, and the virus starts to multiply. And then when the older person's immune system does finally ramp up, it starts to attack parts of the body that it shouldn't, you get senescence cells, which are part of ageing itself, and then it doesn't switch off very well. And so you can have the body doing more damage to itself even than the virus does. And why the body doesn't fully turn this off? We can get into the details of why I think it might be. But it is a fact. And that's why treatment with these anti-inflammatory steroids is one of the things that they do for the elderly trying to tell the body, ‘Calm down, it's not that bad.’

SS: But let's talk about treating with anti-ageing pills. So the old age is a huge risk factor for Covid, should elderly people along with masks, social distancing, other measures, take some kind of anti-ageing pills which would boost their defences?

DS: Well, I don't make recommendations. I'm just a PhD studying mice, but I can talk about the science. The science says that if we were to reduce the age of the body, it should function like a young person’s, there's no reason why that shouldn't be possible. And there have been molecules, one of which, for example, is called rapamycin that in low doses was shown to boost the older people's immune system. And there are other ways of doing that. The molecule that I work on, called NAD, when you replenish that, it's thought to improve the body's immune system and make it younger. And in fact, I work on mice, but I also work with a company that I co-founded, that is doing clinical trials across the United States, in more than 28 hospitals, trying to see if rejuvenating the immune system, making it younger through raising NAD, this molecule, will help in not just eliminating the virus but preventing that overreaction to it.

SS: What kind of time span are we talking about? I mean, the anti-ageing supplements that you're researching, that you're promoting, which are so far not being certified as medicine, but they surely don't work overnight, right? Unlike masks or social distancing, I mean. How long before we can prove a definite connection between anti-ageing supplements and human resistance to Covid?

DS: Well, so most of the treatments that we have, or even the theoretical treatments, which are sold as supplements, work through mechanisms of slowing down ageing, turning on the body's natural defences against disease, which is still a big deal. We've only been able to do that for the last 15 years in animals and in humans, we think we can do it somewhat, there's not a lot of evidence, but there's retrospective studies of people taking a drug, for example, called Metformin for diabetes, which looks promising at slowing ageing. But to work rapidly, we need something that will reverse aspects of ageing. And it looks actually like drugs like rapamycin, and potentially these NAD-boosting molecules, I mean, they won't make you look 20 tomorrow, that's not going to happen, but they can target parts of the body, such as the immune system or the lining of blood vessels and make those cells behave as though they're young very quickly. Just to give you an example, when we treat mice that are old with a molecule that raises NAD, just in about a week or two, those animals are now as fit and can run on a treadmill as far and as fast as a young animal. We think that with Covid, we can have benefits within days. That's so far what the early results say. Ultimately, we want an age reversal, injection or a pill, that's, of course, what the ultimate dream would be. We recently had a paper, it was on the cover of Nature magazine in December, that showed the first evidence that you can rewind the clock, the body's epigenetic clock called the DNA Methylation clock, sometimes known as the Horvath clock, you can rewind that back, just very quickly, within a matter of a week or two as well. And that might be a permanent reset and then you just age out again and keep doing that reset. To be fair, we did it in mice, we did it in the eye and skin. We haven't done it in the immune system but we're hoping to try that too.

SS: So before we go on with Covid, because I'm a girl and I need to ask – you’ve actually seen it with your own eyes that in a week's time someone's skin can rejuvenate and be rewound back to like young age? 

DS: Oh, I wish that was true. You know, we can rewind skin cells that we grow. And we're now doing what are called skin organoids, which are models for skin, and then we'll move on if that all works to turn back the clock in the skin as well.

SS: You’ve got to let me know once that happens.

DS: Yeah, well, we need to figure out a better way of doing it. Right now it's a gene therapy. And I think a gene therapy for beauty would be extreme. But the biological principles are still there that the body has a memory of youth that we can tap into by turning on a combination of just three genes. And it should be possible to do that with small molecules that you could put into a cream one day.

SS: All right, so you speak a lot about the NAD+ molecule, last time we spoke about it in detail. It's a molecule that boosts our longevity genes and protects us from ageing. So tell me this, is just taking NAD+ going to help me with all of those destructive processes, help restore health, vitality? Or do I still need to cut down on bad habits, exercise, eat healthy, you know, all the boring stuff?

DS: Well, so the scientific answer is we don't know the answer to that. But what I do is I do a combination of those things. We do know that exercise and fasting are beneficial to the human body. So if you want to place bets on longevity, those are good ones, even though they're boring and sometimes painful. And then the supplements, what I think is that they enhance that. I mean, very few people do perfect exercise or perfect fasting and these could enhance that. There's a little bit of data from my lab where we did the NAD boosting in combination with exercise, and they added to each other, the benefits. And resveratrol is the same, if you do resveratrol on its own versus fasting, they both have health benefits; if you do them together, we saw a lifespan extension, quite a big one in old mice. And so, again, I think that all points to the combination being the best bet.

SS: Because I'm thinking, on the other hand, if you cut down on bad habits and only eat vegetables and exercise and never smoke and never drink, I mean, just that it's sort of a combo, perhaps, that, you know, would allow me to live long and look great and I won't probably need any pills if a person is able to stick to that all their lives. Do you know what I mean?

DS: It's a good start if you just don't do the five things that doctors – Well, if you do the five things that doctors tell you to do –

SS: Which is?

DS: Well, I knew you were going to ask me that. My recollection is, obviously don't smoke. Don't be obese. Get exercise. Eat the right types of food, which would be mostly focusing on vegetables and not transfats, all that other bad stuff. And then I think the last one was mental health. I can't remember if it was good sleep or lack of stress. But in any case, just the things that you read about on the internet or in newspapers, those are pretty basic things. Those alone – if you do those, you'll extend your life on average by 13 years, which is a big deal. So it's not that hard to live longer for most people, but we also know that people who live those healthy lives still will die in their 90s. It doesn't give you the longevity of Jeanne Calment , who in France made it 122. So if you're looking for longer life than 90s, and healthy life, which is the important thing, –

SS: Yeah, I think long and healthy is the key, because you can live till you're 90, but if you're in a wheelchair or you have Alzheimer's, I mean, I don't see the point living that long. Do you know what I mean?

DS: Well, yeah, not only do I know what you mean, it's what I live for. It's what I do with my life, it's my career is to reduce morbidity, reduce disease. And it turns out, if you're not sick, you rarely die. And so longevity goes along with the health, not the other way round. Typically, typically, medicine as it's practised today, in my view, does things the wrong way around: they will treat a) what we call a disease, process that goes wrong, they treat it after it happens rather than before, and they only treat that one disease rather than try to protect the entire body. And so, as a result, we have more and more patients with dementia because we can keep the heart and the cardiovascular system healthy these days much better than we used to but the brain still ages.

SS: I realise maybe this is probably too early to tell but I can't help asking, is there any evidence at this point about the impact of Covid on longevity? For instance, it's known that it causes thrombosis, the creation of blood clots, which is bad for the heart, whatnot in the long term.

DS: Well, in mouse studies, yeah, it does look like it's accelerating the ageing process, the senescence cells I mentioned. But I don't know if it long-term affects your longevity. It really wouldn't surprise me at all, we see what scientists and doctors see: lasting problems in kidneys and in the heart. So it could, if you have a very bad case of it, and you don't clear it, we call it long Covid, it could reduce your lifespan. I haven't seen data on that yet. Though, I mean, that to state the obvious, even if you don't look at that data, and you just look at lifespan in the US, it declined by a year in 2020.

SS: The main concern is, of course, about the vaccines, which after all these months of hope and expectations can turn out to be ineffective because of the new strains and new variants. Yet I've heard from many health professionals that there's no evidence for this so far. You tell me, can this coronavirus mutate to a point where the antibodies from a vaccine or past disease will not protect you?

DS: Yeah, of course, that's the worry that this is an arms race. What happens, it seems is that in people who have the inability to clear the infection and can be sick for months, in fact, this is a breeding ground and evolution inside the body that leads to these new strains. Because, you know, the virus is mutating within the person's body, and if you can't get rid of it, it'll keep mutating. And then all you have to do is have that person with their cocktail of mutants in their body to give it to a nurse and then it spreads. And, you know, we're seeing this in South African strains and Britain.

SS: Right.

DS: And it's gonna continue. A lot of people – when I first wrote on social media and I had a video on Instagram that people looked at, I said, we should watch out for these mutations, it's mutating, and I'm concerned, what happens a year from now, – a lot of people thought that that was, you know, scare-mongering, fear-mongering. And here we are, where a lot of the news is about these emerging strains and probability... I think eventually the likelihood that it will get around the vaccine and will become endemic, meaning it will never leave this planet and we’ll have to continually make new vaccines every two, three years like we do for the flu.

SS: But the vaccine rollout makes you optimistic that the worst is behind us? I mean, it seems to be working already in Israel, United Kingdom, right?

DS: Oh, sure. I'm very optimistic. A year from now, we may not be talking about Covid. But to eliminate it from the entire planet I think is dreaming, there are just so many people infected around the world now. And it will continue to mutate in the background, and eventually, it will break out again. And so we'll just have to be better ready next time.

SS: Since Covid was such a surprise and hit all over the world, medical professionals couldn't provide clear guidelines on how to deal with it right away because no one really knew. And amid the confusion, it seems that the trust in doctors in general, through this thing, just isn't there anymore. Do you know what I mean? On one hand, we have you know, the nurses and people who are like on the frontlines, and we see them as heroes, but that the doctors themselves couldn’t have answers and don’t know the reasons why, it seems like people don't really trust them anymore. Why?

DS: Well, that sounds like a shame. It's the doctors and the scientists who supply them with medicines that are saving the planet. So at least in my circles, but you know, I tend to hang out with doctors and scientists, so I have a biased, selective view of the world, if people are angry with doctors, I would say that's unfair. You know, we've had the worst pandemic in 100 years, and they were very quickly trying to figure out the best way to treat it. And I thought they did a very good job of figuring out how to do that: the ventilators at first and then putting people prone, face down. These are things you learn along the way. It's not like we have as doctors an answer to everything. We're all human. And as a planet, I think we did well. Where we didn't do well was politically, particularly in the US, it was disorganised, misinformation and so that was a shame. But doctors, I think in general, not all of them – some of them, didn't know what they were talking about either and through the media and social media confused things, but some of the doctors that I know and so on, reputable TV programs did a great job.

SS: You know, I hear all around, like, ‘let's learn our lesson,’ ‘let's prevent the next pandemic.’ Pandemic warnings have been ignored before. But after such a splashy entrance of Covid-19 do you think pandemic doomsdaying will attract a lot of more attention and reaction? Do you think we're actually going to take this seriously and be prepared if something next is up? Or will everyone just forget about the whole endeavour once we get our vaccines and everything calms down?

DS: Well, let's hope that we learn our lesson because the next one could be much worse. Yeah, something that comes out from the forests of Africa and could potentially kill 10% of people and be just as infective is not really just a possibility, it's going to happen at some point. We have to be ready. Now, I'm optimistic because Southeast Asia, Asia in general was much more prepared for SARS than we were over here in the US and I would say most of the rest of the world because they had experience with it, they feared it, the population knew it was very serious. That's one of the reasons they did better. And yeah, hopefully, we do learn and that we'll be prepared and we'll have stockpiles and we'll know how to ramp up industries that we need again, and we'll have better technologies that can track viruses that emerge early and be able to test for them and follow them much better. This was part of our problem here is that trying to get testing up and going was also not done very efficiently.

SS: What is and isn't being done right now to prepare for and perhaps prevent the next pandemic, in your opinion?

DS: Well, so I can speak with some authority on that, in this case. So there are a number of programs to track viruses in the environment and in the population. And not just where it is, and how often it occurs, but what type of virus and even down to the strain level, we need to know that if it's mutating and potentially becoming- it can skirt our immune system and our vaccines. So one of the things that I've done, actually, I started about seven years ago is a virus tracking company. In fact, it tracks all pathogens, not just viruses. You can take a swab of the mouth or a blood sample, and they can tell you every thing that's not human in the body, which is I think the way microbiology and medicine has to be practised in the future. And so companies like that one, that one's called Arc Bio, there's other ones, will serve us as surveillance in the United States. I think, I would hope that the world has a much better global surveillance of viruses so that we can be forewarned and not play catch up so much next time.

SS: David, it's always so wonderful to talk to you. I love what you're doing. And actually I have so much faith in you. Thanks a lot for this wonderful insight of what you think of Covid and whatever is going on and what we're doing or not doing to be prepared in the future. And I really hope that we get to do this again soon. And good luck with everything. 

DS: Thanks. It was good to see you.

SS: Thank you. Bye.

DS: Bye.