Bhagwati Gupta – Organism Lifespan and Genetics

Transcript:

Im a Mortal Episode 13: Bhagwati Gupta – Organism Lifespan and Genetics Transcript

Speakers: Bhagwati Gupta (Guest), Sufal Deb (Host), Marvin Yan (Host)

[MUSIC – Im a Mortal Theme]

Bhagwati Gupta  0:27  

Hello, my name is Bhagwati Gupta. I’m a professor of biology at McMaster University. My lab at McMaster is now more than 15 years old and over the years we have undertaken different projects and published lots of papers. The main theme of our research is— basically two actually. One is how organs develop in animals, what genes and mechanisms, signaling mechanisms are involved, and how genes control animal behavior. Related to that, we have also gotten into a new, very exciting area of research more recently, which is how genes control the stress response. This is something that we feel would be a major thrust of my research in the future years. The stress response affects the health and lifespan of animals. That’s something that I would be able to talk to you about. These research questions in my lab involve taking multidisciplinary approaches, and lots of collaborations with researchers, both from Canadian and international universities. The training in my lab, through these multidisciplinary approaches, has benefited lots of graduate and undergraduate students. Students have gone on to successful careers, both in academia and industry, which I’m very proud of.

Marvin Yan  1:53  

Okay, one question we always ask at the beginning, regardless of the person’s background is, what does immortality or the word immortal mean to you?

Bhagwati Gupta  2:00  

That’s a good question. The literal meaning of immortal or immortality is that you’re living forever, right? But to me, it’s more of a psychological or philosophical concept, because no organism can be immortal, right? It’s more about being alive even if you’re not physically alive, right? That’s what immortal to me means. That would be by doing things like leading or participating in activities or making significant contributions that keeps your name alive, even after you’re not physically living on Earth. Maybe a good example would be a famous scientist that I always admired, Albert Einstein, for his groundbreaking work related to relativity and the light. They’re still relevant today. Einstein is not with us, but we still talk about him very regularly, right? So that’s what immortal or immortality means to me.

Sufal Deb  2:54

I have a two parter question for you based on the answer. Number one is, if you had the chance, would you like to extend your life to, let’s say, 500-1000 years? Additionally, would you like to be immortal, according to your definition? 

Bhagwati Gupta  3:07  

Yeah, according to my definition, immortal, yes. But in a physical sense, I would say I would be more interested in extending life, but not being really immortal. But also, extending life has a catch. There’s no point in living longer if the quality of life is poor, right? One may be living longer, but bedridden, or need to rely on others to perform daily functions and that’s not a good thing. Now, note that I’m not referring to being poor in terms of not having enough money, or a health condition that affects people in the early stage of life with lots of these genetic disorders people have— that’s a completely different thing. What I mean is extending life, which I’m interested in, is having a better healthspan. In biological science or terms, we use something called healthy ageing. It’s not only living longer, but also maintaining health span. You can carry out your normal activities reasonably well and be independent. Your muscles are functional, the neurons of your brain are active, and your physiological functions are in a good state. It’s also worth mentioning— related to this is something that we talked about this physiological or biological age of living systems and chronological age. Chronological age is defined by when you were born and how old you are, whereas your biological age is how old your body behaves. These are two independent things and affected by lifestyle or medical interventions. For example, a poor lifestyle might result in one being younger based on their date of birth, but their body may be much older physiologically, and that’s an important thing.

Marvin Yan  4:50  

Okay, this is a good transition. In terms of age, a lot of scientists get asked this question, and people have a lot of different answers. They always have this question of, is biological ageing a disease, and we’re just wondering what your take was on that.

Bhagwati Gupta  5:02 

That’s a good point. Ageing, I don’t think is a disease. Ageing is the result of the breakdown of processes over time, and how much you use your organs, and so on. It’s more a decline of cellular processes, molecular processes, and it is a natural thing. It’s non-specific so all organs are affected in the body. Although, there might be times when some organ is accelerated more, aged more for whatever reason, and might then affect other parts of the body. But generally, this is an overall decline in the fitness of the organism. I like to think about it, that our genes and proteins, or molecules in our body, or cells are little machines, micromachines. They are continuously active, doing functions non-stop. They are continuously used and combined with external factors, such as the food that we eat, the environment that we live in, that cause these machines to slowly become less efficient with time. Why is that the case? There is a very interesting evolutionary aspect to that. We can elaborate on that more later on. Evolution basically selects living systems to allow them to just reproduce, so you can survive and propagate population growth. That is all that evolution selects. These little micromachines, and in turn the cells, organs and the whole body are just selected to be able to pass on our genes and reproduce. After that, those cells could die or become less efficient, organs could fail, and so on. Nature wouldn’t care. In a way, ageing is a consequence of these machines being less efficient over time, because nature is not selecting them.

Sufal Deb  6:53  

Just quickly, since we’re on the topic of genes and we’ll jump back later, why is it that we’re programmed for our organs to age? Shouldn’t our genes be thinking of refreshing our organs, or refreshing themselves, so we can live longer?

Bhagwati Gupta  7:05  

Yeah, so that’s also related to, as I said, about evolution selecting these machines to be efficient, for only a specific purpose, which is to pass on the genes and beyond that, it is not selected. It’s like, we, as humans, make certain products or objects with certain purposes. If that purpose is served, we don’t care how long the object is actually going to be functional or not. That’s exactly what it is. Nothing— I would say philosophically, as well, that nothing is designed to last forever. Everything is just selected for a certain function, a certain purpose. That purpose is done and after that, it is no longer selected. If you want something to be functional forever and be in a good state, it needs to have a lot more elements to that, that make it more robust, over and over again. If something starts to break down, there has got to be some compensatory mechanism to make it functional. Those compensatory changes would actually have to occur during evolution. It creates changes in our genes, in the DNA, which changes the proteins that could remain functional. What has happened so far is that nature selected these proteins or molecules to perform certain functions and hasn’t cared about making them robust forever. They do their job and over time they become less and less efficient. Then they fall apart.

Marvin Yan  8:29  

As a follow-up to that, you explained that you only need your body to work for as long as you need to reproduce, right? But then, how is it that evolution has some animals living a matter of days, maybe even hours? I think there’s some— Sufal, we talked about some other animals that are biologically immortal. Why are some [lifespans] so short and what’s the point of having some creatures that are “biologically immortal”?

Bhagwati Gupta  8:55

It’s puzzling why some animals, or some living things, like bacteria, live for only a few minutes, and other organisms can live for hundreds of years. It’s an interesting question. I don’t think there is a universal answer to that. So, why can you do that? Well, if you think about it, every living system has a unique environment that they live in. They have certain nutritional requirements, they have a certain competition for survival, their food sources are limited, their environment is more hostile, they have different levels of stress. Depending on the conditions that they are dealing with, it will impact the ability of these Micro Machines. If somebody is constantly dealing with distress and always having challenges. They would end up consuming a lot more energy in a small amount of time. Much smaller organisms are much more vulnerable. You would see they have a shorter lifetime. Basically over time, during evolution, these things have been selected to only perform certain functions. Nature has also selected them and allowed them to reproduce very fast, because they’ve only got such a short period of time to live. But humans, we have a longer period of time and that’s because we are able to, during this time, grow, mature and reproduce. Then after that, whatever happens, is a consequence of how we treat our bodies. 

There’s also other components that come in. The kind of food that we eat, the exercise that we might do, or the better quality of life that we might have. All of those lifestyle changes that we have, those will contribute to how long you live, but as far as nature is concerned, it selected us only to reproduce. If you look at humans 100 years ago, the mean lifespan used to be very short. Then, as technology has evolved, medical science has become more and more advanced, the lifespan has consistently increased. Now, you see humans that can live over 100 years, some of them. Researchers have mapped what the risk factors are for people as they get older. As people get older, they’re more susceptible to diseases, and as people get older, they can have one disease, two diseases, or three diseases. As they get older, they can have multiple problems. The risk factor continues to increase as people get older. Death is just stochastic, as they get older and have multiple risks. Sometimes, stochastically or randomly, one of the things just takes over and causes massive organ failure and could result in death.

Marvin Yan  11:35  

One follow up to that, which is— if evolution just wants us to reproduce, make the next generation. Humans are the first example but we seem particularly bad because we can’t reproduce for the first several years, more than a decade, right? Why is it that evolution hasn’t made us all be able to reproduce within like a day or two?

Bhagwati Gupta  11:55  

Yeah, that’s another interesting, interesting question. If you look at different organisms, and how those organisms develop, you see the different levels of complexity, right? More complex systems need more time to develop. In the case of humans, it takes nine months for babies, starting from a fertilized embryo, to become fully mature. It takes that much time just because— even though Micro Machines are working continuously, just as fast as they do in adults, right? But it’s just that the amount of work that they have to do is just enormous. It takes so many months for the fertilized embryo to become a mature baby. In order for us to be able to successfully give rise to babies, we have been selected to live at least long enough, that allows us to not only fertilize an embryo to give rise to babies, but also take various chance factors that take into consideration that one might not reproduce on day one, right? It might take several years to reproduce. 

During evolution, all that matters is whoever is successful, the best fit will survive. If they’re not successful, they would basically go extinct, right? Humans have survived because humans were able to reproduce in that period of time and were slowly selected as Homo sapiens. There are many related species to humans that came into existence, but then got lost. Nature has been working continuously to select the best population and Homo sapiens is the ultimate output of that. Now, that doesn’t mean that the Homo sapiens humans might not evolve, there may be smarter humans, who knows? As technology continues to evolve and our brain works differently. Our body parts work differently, right? 

If you think about that, the earliest humans used to just be hunters. They lived in the forest, they just hunted for food. Our bodies basically evolved to utilize whatever they ate to produce energy. The fat that is considered bad nowadays, well, it wasn’t bad when humans evolved because humans might find an animal today that they could kill, but then they might go hungry for several days or weeks. The body evolved to utilize fat, that it would break down and produce energy when they’re not getting food. There was no storage possibility but now we have a very good lifestyle, very safe, very secure. The body still recognizes fat as a premium product. When you see fatty stuff, your saliva gets going. You like fried chips, the body is still thinking that we’re living in the stone age, but in reality, it’s not. As a result, we’re not breaking down fat as fast as the ancestors used to do, so fat accumulates in our body. 

Things that we consume faster, carbohydrates or glucose, that break down like that. Our brain is designed to use glucose because it’s an instant source of energy, but for the rest of the body, it’s okay if you’re moving a little bit slower. As long as there is no threat, and if there is a threat, obviously, you have to run fast to survive. But other than that, you can survive by breaking down fat, which takes more time to break, because it’s a slower process, more energy-consuming process, and would allow animals to live longer. It’s a very interesting evolutionary angle.

Sufal Deb  15:17  

Okay, before we jump into other questions, I have a couple of thoughts I want to bring up and try to form into a question. Earlier, we were mentioning reproduction— and this isn’t based on any hard data or statistics, but from what I’ve noticed, people tend to, especially in first world countries, value education over starting a family, which leads them to having children in the later years of their life. Obviously, for females, they don’t have reproductive abilities after a certain point, they hit menopause. Is this trend of valuing education and career and having children later in their life than in the past, almost against what we should be doing genetically or to increase our fitness?

Bhagwati Gupta  15:54 

Yeah, that’s another interesting question. My colleague, Dr. Singh, Rama Singh, he works on the menopause-related. He would be able to give you more insight into that, but from what I know and based on his research and other people’s research, menopause basically evolved because nature selected for females to reproduce at a certain age, and after that, they were not reproducing. Therefore, mutations accumulated in those genes and are no longer necessary for reproduction. Why spend all that energy maintaining those tissues and cells when they are no longer in use? If humans delay reproduction, because they have other things in their life that are more important, that they’re more interested in, I wouldn’t be surprised if menopause slowly shifts to an older stage, older age in life, because it is going to get slowly, slowly selected. The difficulty with understanding this concept is that evolution is a very slow machine. We, as humans, have a tendency to see results or want to see results very quickly, in a matter of minutes, or hours or days. For us, it’s very hard to understand how could that be possible. But believe me, that’s what has happened so far and it is continuing. Humans are continuously evolving, as we speak.

Marvin Yan  17:11  

Okay, just jumping back before we move on to evolution. Earlier, you mentioned fat. I’ve seen that— I think it was my former TA, I don’t know if he’s Dr. Malik yet. You guys were featured on the McMaster website for your work on lipid metabolism. I was just wondering, what is the link between lipid metabolism and ageing?

Bhagwati Gupta  17:30  

That’s an interesting angle. Obesity is one of the highest risk factors for mortality. It has been found that, as I said, our body has evolved to utilize fat and convert that into energy. There are a lot of processes in our body that depend on fat, and not just energy, but also cells that are lipid bilayers, right? They need fat, the various other proteins that get modified and so on. There are many uses of fat. But if you have too much fat, then that’s also bad, because cells will need to take care of it. What will they do? They start to accumulate those fat molecules in different forms. When they’re just no longer able to, the fat would start to distribute in other parts of the body, which is what results in obesity. On the other hand, the faster breakdown of fat is also bad, because then you’re losing energy much faster than needed. Lipid metabolism research that we’ve done is about balancing the energy. Production and consumption. Animals can grow, utilize fat, mature and live longer. If you disrupt either production or breakdown of fat, you end up with this imbalance, both of which are bad. While too much accumulation of fat, which is a poor breakdown, can result in obesity or other kinds of problems in cells, not just obesity, but other types of problems that cells will have because they can’t modify their proteins and so on. But, also not having enough fat is also bad because the cells and tissues need that. In that sense that research is very interesting.

Sufal Deb  19:08  

Obviously, you’ve studied lifespan a bunch. What is one of the most interesting things you have found while studying lifespan and age? How did it come about and what does it mean for humans like us?

Bhagwati Gupta  19:18  

Our research on life span and ageing started from work that we did on one protein, which is generally a family of scaffolding proteins. Scaffolding proteins are proteins that have different domains. They actually are able to recruit other proteins to form bigger complexes. Then, these complexes will perform different functions. They act more like a docking site. They are able to bring in other— they act as a glue. We found that when you disrupt the function of this protein— and we did that in nematodes, but this protein is conserved in humans, too. When we disrupted the function of this protein in nematodes, what we found was that animals have a shorter life span. This means that they die faster. They have a higher level of distress, a variety of stress. We describe the stress in biological terms that are associated with organelles like the mitochondria, or the ER (Endoplasmic Reticulum), but also cytosolic stress that involves a role of the [unintelligible] protein, heat shock proteins that function to protect various proteins in the cells and other processes as well that this protein is involved in. 

That was the initial work that got us into the stress response and the ageing field. That’s something we found very interesting. Here is one protein, that when you don’t have this protein functioning properly, a lot of these processes are disrupted. We did more work on this and we found that one of the processes that this protein controls is the functioning of muscles. You know that if the muscles aren’t functioning properly, or degenerating faster, it could result in a lot of disorders and affect the mobility of animals. We found that this protein is— molecularly, whatever it does, ultimately results in the maintenance of the muscle function. If you don’t have this, the muscles degenerate faster and that causes— somehow links to the stress level going up and causes animals to die because they’re not able to move properly, not able to feed properly and all these other complications that happen that kill them. This aspect or function of this protein appears to be conserved in higher animal systems. We find that literature says that this protein also seems to be important for muscles in humans, we don’t know if it plays exactly the same role and that is one of the areas that we are very interested in investigating. How much of this protein function will be conserved in humans, in terms of maintaining mobility, muscle health, and so on. We find that research very interesting.

Sufal Deb  21:49  

You mentioned that you studied nematodes. Why nematodes? Are they ideal for studying ageing?

Bhagwati Gupta  22:46  

Yeah, nematodes have been at the forefront of ageing research. In fact, most of the initial discoveries came from the nematode system, and that, I think, has to do with a few characteristics that the nematodes have that offer advantages. One is that they have a shorter life span; they live about 20 days or so. Whatever manipulations that you do, you see the results within a matter of two to two and a half weeks. The mean lifespan of nematodes is about 15 days or so. You get results very quickly, and it allows you to come up with newer questions and you can address those questions faster. 

The other advantage that it has is that it has got a transparent body so you can see the organs, even in alive animals. If you’re changing the function of a gene, manipulating genes, you can see how those genes are affecting different organs. Biologists or researchers really like to investigate where the genes are functioning, which organs. For that, we look at the localization and all of that we are able to do in live demos, because we have this green fluorescent protein. These are fluorescent proteins, and we don’t have to sacrifice animals. We can examine where this fluorescent is located, which part of the body and we can then tell which tissues, which organs are utilizing these genes. Transparent-bodied animals are very advantageous. 

Another thing is that it has a fully sequenced genome. As you know, the genome is very useful in inferring the function of genes, their networks, and lots of other things. Nematodes happen to be the very first multicellular organisms that were sequenced. The nematode sequence is of very high quality. Not only do we know the sequence, but we also understand a lot of those sequences, what proteins they make so all of these and many other experimental advantages, have made nematodes an excellent system for research on ageing and research on the stress response pathways.

Marvin Yan  24:01  

We just talked about your research on ageing, and looking at ageing applied to humans, a lot of the leading researchers in the science field who are speaking out about how to possibly fix ageing. They’re usually talking about the damage repair approach. I was just wondering what your take on it was, because this is more of a, “Let the proteins accumulate, and then we’ll get rid of them” or “There’s a cancer cell, we’ll get rid of it”, rather than starting from the genome or genetics level. What’s your take on that approach?

Bhagwati Gupta  24:28  

Yes, given that the pace of research can only be so fast, I believe that we have got to take a multidisciplinary approach as well as working on multiple fronts. In a shorter term, you not only want to gain a more fundamental understanding, which could then help develop drugs and so on, but you also want to take care of people who are getting older. You have got to find some quick-fix solution if there are, you know, say Alzheimer’s or Parkinson’s patients. These are also age-related neurodegenerative diseases, cancer, which is also an age-related disease, you have to find drugs, so you can treat people who are right now— directly something that improves the quality of life for those patients. But then, on the other hand, you have to embark on more fundamental research. What are the genes involved in this, what are their mechanisms, interacting partners, and so on? We can then target those proteins, those components with certain drugs, and then try to either establish their function, or if they are bad, then break down their function. They can have a more comprehensive approach, a more foundational approach to increasing the quality of life and the health span of animals. It has got to be multifactorial on different fronts.

Sufal Deb  25:42  

How much do genetics play into the factor of living longer or just longevity in general?

Bhagwati Gupta  25:47  

A lot, actually. We just talked about why different organisms have different lifespans. It’s genetic factors, environmental factors, and the lifestyle of organisms. All of these come together to affect the lifespan. Genetics play a very important role. If our body is not capable of fighting certain infections, then you might not survive. Even in humans, there are variations. As we are dealing with COVID, the mortality rate is about 2% or 3%, something in that range. It varies from country to country. Also ethnic factors and geographical factors. The majority of people are actually fine, right? They don’t have problems, so you wonder, “Why? It’s the same virus getting into everybody’s tissues and they’re inside their body, but only a few people have symptoms, and very few actually end up developing serious diseases and die?” 

Genetics play a very important role and there are variations. Even at that level, you might say philosophically, that nature is selecting. Whoever is weak is going to die and whoever is strong will survive. People who survive, presumably have a better genetic system, and they’re able to now have more opportunity to pass on their genes to their offspring, who hopefully will have an even thicker genome, who will then in turn be able to pass on their genes. People who had a poor genetic system, less efficient have died, they were not able to pass on their genes. This is how basic evolution works, right? It slowly selects more efficient systems. Over a long period of time, you see a massive impact. For quite some time, these things happened within a threshold, you don’t see a major impact. But after that, you see a sea of change, and the virus will probably not be able to infect populations that have survived and are resistant.

Marvin Yan  27:43  

Okay, I have a bit of a personal question, and it’s for my own understanding. So listeners who are listening, maybe you had the same question too, but we talked earlier a bit about cancer. I always thought cancer was more of a time-related thing. Even if you don’t age, you always have a chance of developing cancer, just because— by chance, right? I always thought cancer was time-related and not age-related. But then how is cancer specifically an age-related disease rather than just being a function of time?

Bhagwati Gupta  28:10 

Yes, so I think in your question, there was a little bit of an answer embedded so age is nothing but the passing of time, as time goes by, you’re getting older. When you say that, “We want to extend life and then you’re not ageing.” Actually you are ageing, but it’s just that your lifespan has become longer. So, yes, you’re right, that cancer in the most fundamental sense— the ones that are caused by mutations in genes, because there are other types of cancers. Genetic cancers that can result from spontaneous mutations in genes as cells are dividing and DNA is replicating. It is definitely by chance, and early on Micro Machines are repairing those mutations. As time goes by the repair machinery also becomes less and less efficient. Just like somebody is making 10 mistakes and in the beginning, they’re able to correct all those 10 mistakes. But as time goes by, they’re correcting less and less mistakes. Whatever is left behind has a chance of doing something bad. Now it’s not necessary that they will do bad things every time, but sometimes they could. Cancer is also by chance. It’s a matter of time. As you get older, as time goes by, more and more chances are there that you’re likely to hit some very important gene and that could result in the triggering of the cancerous disease. Yeah.

Marvin Yan  29:32  

There are two questions. Could you briefly make the distinction between if cancer is a chronologically based age disease or is it a biologically based age disease? Then second is, let’s say we do cure ageing, the actual biological ageing, not the chronological because we can’t do that. But biological, does that mean to get rid of cancer we have to cure cancer separately? They’re sort of related questions.

Bhagwati Gupta  31:29  

Yes, so cancer typically is age-related. Unless— until there are other types of cancers that are genetic, and then caused by a BRCA mutation that makes women prone to those cancers. But generally, cancer— it’s just by chance the mutations will occur. As people get older and older, their chances of accumulating some spontaneous mutations will increase. If you extend the lifespan, or biological age of people, you’d expect fewer chances of cancerous growth. In human cases, things are way more complicated because we are not only experiencing one type of environment, we live in a very complex environment. 

On one hand, we want to extend our life, have better medications, exercises, and things like that. On the other hand, there are a lot of products that are developed for human consumption, and a lot of them involve chemicals. These chemicals are mutagens. We need more food because the human population is growing. How do you get more food? Well, you need to be agriculturally more efficient, which means more crops. You have to make sure that they’re not infected with insects so a lot more pesticides are being used. Pesticides are toxic and can cause cancers in humans, right? People have lifestyles, right? They’re drinking, they’re having various other kinds of consumption. It’s very complex for humans. We don’t have a very simple lifestyle where we are experiencing one type of thing. I would say yes, scientifically, extending the lifespan should reduce the chances of cancers. But then there are these other environmental and lifestyle factors that are very hard to dissociate. It would be hard to say; the frequency will go down in the future.

Sufal Deb  31:47  

Would you consider cancer as a barrier to living forever and if you do, what are some other things that might be a barrier to living forever?

Bhagwati Gupta  31:55  

Well, so while you talk about cancer, in fact, cancer is not the most deadly disease when it comes to the survival of humans. If you go— most people you’ll see would die of things like malaria, things like diabetes, other kinds of diseases. It’s only in the developed countries where we’re not having problems with those other diseases that are more prevalent in third world countries. If you go out there, look at the world statistics, cancer is not the deadliest disease, okay. Coming back to cancer, yes, we are able to extend the lifespan and with a better quality of life, you can reduce those chances. For a lot of the population living somewhere else, they’re dealing with more basic fundamental issues, and they are more detrimental to them.

Marvin Yan  32:44  

Related to this, obviously, if we could fix whatever mutation that causes cancer, then yeah, you would stop it. But on an evolutionary scale, we know that mutations are not bad, because that gives rise to fitness and all that. But as we live longer, how do you know how much to correct the human genome’s mistakes and whatnot? Where would you draw the line in terms of genetic editing to help us live longer?

Bhagwati Gupta  33:08  

Yes, this is something that has a lot of ethical issues in there, right? There’s a lot of debates happening on how much one would want to correct the genome and now the technology, genome editing technology is available and researchers have even gotten a Nobel Prize this year for that. Where do you draw the line? To be honest with you? I’m actually not quite sure. Because, on one hand, I would say yes, we want to correct the genome to remove diseases like cancer or other diseases, sickle cell anemia, or other kinds of diseases where it is known that there are— Huntington’s, where it’s a single protein and things like that. Then on the other hand, whatever one person thinks is a bad thing, and therefore this should be fixed or could be fixed, for another person it could be a different perspective, right? They might see something that we might term them as more luxurious things that they want. “Oh, I want my baby to not be obese, okay, and therefore, correct all the genes that will make them obese, not make them obese.” One might say, well, obesity is not necessarily going to kill them. Of course, it is a risk factor but for different people, there may be different needs and different desires. How do we reconcile these desires? 

For some people, it could be a very basic, fundamental, real disease that is going to kill their babies. For some, it could be more luxurious, more superficial things, changing the colour of the skin, making them bigger, taller. They could be a better basketball player, right? This is not an easy question to answer. It will require the government to take an approach and will basically have to come down with some sort of law because I think that it is unethical to start tinkering with the human genome and start producing what we call “designer babies”. No matter what you say is a genuine need, there will always be a counterargument to that. Genuine needs differ from person to person, country to country, population to population, it’s a very tough question. I would say that for anything, just to start with, we should not be messing up with the human genome. Let nature and evolution take care of it. When there is a law in place that says, “Yes, the genome could be modified,” we will see at that point what everyone agrees on, or what the majority agrees on.

Sufal Deb  35:35  

We talked about this a little bit earlier regarding reproduction, and the later age of reproduction. With the trend of people reproducing less frequently, less willing to have five or six babies. Maybe one, two, not more than that, especially in developed countries. Are there any ramifications associated with having a slower generational turnover, because of these later babies— later life babies?

Bhagwati Gupta  35:56 

Well, I would say not in our lifetime. In this shorter time span, how many years or hundreds of years does one go back to look at their lineage, right? You go to your grandparents, then great, great grandparents. After five or six generations, you probably don’t even care, right? I don’t see much of an issue that people are going to reproduce slower or less or later in life, because there are other things that come into play for humans that protect individuals. There’s so much support system in place. Even if you’re producing one offspring you have done your job, you passed on your genes. Back in the olden days, humans would reproduce way more, make more and more babies, because there was a lot more chance factor. The death rate was very, very high back in the old days but that’s no longer the case. I think for modern humans, even one offspring means you’ve done your job. As long as the chain is there, your population is growing, your chain is growing. For nature, it’s not about individual chains, it’s about the human race. Nature cares about humans as a whole. We might be selfish thinking about “my race”. But if you look at, say, bacteria or a colony of ants, they might have their own families but for them— for us, it’s the whole ant. It’s just the population so it’s an interesting, interesting way of thinking, but that’s what it is.

Marvin Yan  37:25  

Listen, as long as you reproduce at some point, no evolutionary stagnation. We’re good. 

Bhagwati Gupta  39:15  

Yes. I think so. 

Marvin Yan  37:25  

One final question before we start wrapping up— well a few questions before we start wrapping up. We’ve interviewed a lot of people so far, and they each have their own predictions of what’s going to happen in the next 10, 20, or 100 years. Let’s say, by 2050, right? By 2050, where do you see the progress in terms of longevity?

Bhagwati Gupta  37:45  

I would say that— if I were to predict what might happen in the next 20 to 30 years, I would say that both lifespan and healthspan will be extended. Recently I was reading an article, which basically said that there is no limit to human lifespan. It is a topic that is quite debatable because there are people who believe that human life has reached its maximum. I mean, if you see how old people are living— there are many supercentenarians, right? If you plot them on a graph, age versus time, you see that it’s plateauing. You don’t see people living 150 years, for example, right? But then people do believe that with better quality of life, better health system, better support system, people could keep living longer. I think that will happen. Lifespan and healthspan will certainly be extended. 

I mentioned the risk of death as age increases. People who are newborn babies or teenagers have a very, very low-risk factor versus people who are 80 years old. When they go past 80, 90, or 100, we don’t understand why some people are living so long. What is in their body? There’s a lot of research going on there. I would say, on the technology front, I expect to see a lot of developments supporting a better quality of life, better products, and there’s a lot of research called Smart Systems, to monitor what’s going on around people. The sensors that are checking all the time, are we walking correctly or not? Do we have a chance of falling down? Have we performed all our functions as we expected every day, and if there are changes? All kinds of things. I see that technology is improving a lot and helping the better quality of life. I will say drugs, there is lots of research happening on the front of developing drugs that would enhance the health and fitness of humans. I expect to see many of those coming in the next 20-30 years for sure. Yeah. 

Sufal Deb  39:48  

Speaking of the future, I’m sure there are a lot of students and younger individuals listening in right now. They’re interested in tackling the biology of ageing and all these other fields. What is the best way for them to get involved? Is there a specific field that you think is more promising— or not more promising, but very interesting and might be of interest to someone listening?

Bhagwati Gupta  40:05  

Yes. First of all, a lot will depend on the interests of individuals. If you’re interested in the biological aspects of ageing, then, of course, you want to start out by reading some basic articles, and so on. There are lots of good articles that come in more general magazines, and so on. Then including some scientific papers as well. Start out with reading that, see where that kind of research is being done and try to communicate with those people to see if you could get involved. Then if you’re interested, say, in the social aspect of ageing. How to manage the older population, how to provide resources to them. Even linking to government policies, how municipalities or cities handle the ageing population, and how that translates into better homes, a better quality of care. That’s another angle of ageing. Then there’s a technological angle, which I just mentioned, that people were more interested in engineering. To have that kind of inclination, they could look into technology development. 

I will say, the first thing to start with, depending on the interest, is to try to find some general articles. There is a lot being written these days. Then from the general article, you have to go a little bit more into actual research papers. Then again, there are some magazines or even websites that provide more easy access to research without getting too complicated. Then you get into a little more and then start to see what is available closer to you that you could get involved with. The good thing now is that in the COVID time, Zoom and the Teams and other video channels have become more accessible. It might be possible to meet with someone who works on that. If you’re passionate about that, people would look into you seriously. I mean for a researcher like me, I want to see how passionate a student is— or someone, not just necessarily a student. That could be people who are looking for a change in their career and they want to get involved. I’m interested in seeing how passionate the person is, if they have looked into my area of research, and are able to rationalize why they think that research is appealing to them. I’m sure that, not just me, but many of us would be willing to talk to them. 

Marvin Yan  42:14  

We’ve discussed a lot. Whether it be how much fat you should have or do your part and reproduce at some point. Is there one single takeaway you want listeners to have?

Bhagwati Gupta  42:22  

I would say boiling down everything to one thing is obviously challenging. But I would say that I’m very interested in healthy ageing. I think that is the most important thing, not necessarily living longer. Whatever lifespan that you have, you’re most fit, you’re able to do things, and you’re enjoying life. I would say whatever activities one does, they should look at them from the angle of healthy ageing. Whatever your diet is, whatever your lifestyle is, everything else, just try to make sure that you remain fit, you remain healthy. I think that’s something that I’m more interested in.

Sufal Deb  42:57  

Thank you for coming on. But before we wrap up, if somebody wants to talk to you or learn more about your work, where can they go?

Bhagwati Gupta  43:02  

Yeah, I would say that there are several websites through which I can be accessed. We have a departmental website, if you go on the Biology McMaster website and look into researchers you will be able to find my name, my research and contact information. There’s also— McMaster has a McMaster Experts website which is experts.mcmaster.ca and if you search my name you can find me there and contact me through that. We also have websites that we manage on our own. One is my own personal website which is bhagwatigupta.net. There is also our lab website www.macwormlab.net, which our students maintain. We have some research data there and names of trainees that are involved. Those are different, very different means. I guess the simplest thing nowadays could be just to go out and Google my name and through McMaster and build upon it. That would be the simplest. These other websites can give you more information about the research that we do for sure.

Marvin Yan  44:03  

Okay, so then for all you guys listening, these links will be in the description below. Once again Bhagwati, thank you for coming on Im a Mortal, your source for all things immortal. We really appreciate you coming on to talk with us today.

Bhagwati Gupta  46:05  

Thank you so much. I really enjoyed talking to you. It’s been fun. 

Sufal Deb  46:09  

As did we, thank you.

Bhagwati Gupta  46:10  

Take care.

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