808: Unraveling How Mitochondria Can Be Used to Reverse Aging and Treat Age-Related Diseases - Dr. Keshav Singh
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Hey, everyone. Thanks for joining me today for Episode 808 of People Behind the Science. I'm your host, Dr. Marie McNeely. And today I am joined by our guest, Dr. Keshav Singh, to talk about life and science. This episode is made possible with support from our sponsor, Innovative Research.

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And today, our guest, Kashav, is going to tell us more about his lab and his life. So listeners, get ready to meet another one of our outstanding people behind the science. Every day, discoveries are made that will change our understanding of the world around us. Dr. Marie McNeely is here to bring you the brilliant minds who are making these discoveries so they can share their incredible stories and take you on an amazing journey. Welcome to People Behind the Science.

Thank you.

Hello, everyone, and welcome to People Behind the Science. Today, I am excited to be speaking with our guest scientist, Dr. Keshav Singh. So, Keshav, welcome to the show today. How are you? Good, thank you. Glad to be here. Well, thank you so much for joining us. We're excited to have you and excited to learn more about you and your work. But before we do, I'd like to take a moment here to tell our listeners a little bit more about your background and how you got to your current position. So,

So listeners, Kashav is the Joy and Bill Harbert Endowed Chair and Professor of Genetics, Dermatology, and Pathology at the University of Alabama at Birmingham. He is also the founding editor-in-chief of the Mitochondrian Journal. In addition, Kashav is the founder and chief scientific officer of the company Yuva Biosciences.

Keshav began his studies in India, earning his Bachelor of Science degree in microbiology from Roquehilken University and his Master's of Science from J.B. Pentt University of Agriculture and Technology. Next, he moved to Australia and was awarded his PhD in marine biology from the University of Wollongong.

Kashav then conducted postdoctoral research at Harvard University before joining the faculty at Johns Hopkins University School of Medicine. He later moved to the Roswell Park Comprehensive Cancer Center and served as Distinguished Professor of Oncology. Next, Kashav joined the faculty at the University of Alabama at Birmingham, where he is today.

He is a fellow of the Royal Society of Medicine and a member of Sigma Xi, the Scientific Research Honor Society. And he's also been recognized as one of the Innovation Heroes by Newsweek. And Yuva Biosciences was the recipient of the Company of the Year Innovation and Excellence into Mitochondrial Science Award at the University of New York.

at the Indian Icon Awards. And in our interview today, Keshav, we're excited to get to know about your scientific side, but we'd also like to get to know you as a person more generally. So can you tell us what do you like to do when you're not doing science?

I love to fly tight on the beach, travel, painting, and mostly scientific painting. I'm in love with mitochondria, so I paint all different kinds of mitochondria, such as sold some of them on eBay. And those paintings are mostly when the experiment don't work in the lab, I find a creative way to do the painting and see what experiments may work tomorrow.

I love that. I think this painting, the art side of science is remarkable. There's so much visual aspects in the science. I think that you do in particular, these mitochondria are just remarkable and beautiful. So what inspired you to paint them? It's partly because when I started a journal called Mitochondria in 2000, I got a large collection of mitochondria people send me because I was deciding what to put on the cover.

And that got me interested because there are so many different types. Actually, I put it on LinkedIn. I said, there are mitochondria for every occasion. So on Valentine's Day, I have mitochondria with a hardship. It's on LinkedIn. That got me really excited. So, okay, now I can, one, utilize the EM to, you know, all the electromicrograph pictures to paint those. And then I have my own imagination in different shapes and forms. And then what they're doing is skeletal muscles, what they're doing brain.

And sometimes just with my daughter and son, we make up mitochondria. I think that is so cool. So you mentioned you love to paint. You obviously spend a lot of time doing your science and you also like to hang out and just relax on the beach. I think this is a wonderful way to blow off steam, pull that kite out and run around a little bit and have some fun. Yep. In fact, when I was in Boston, I flung kite in middle of winter. Oh, wow. I got the urge, okay, I got to fly. So well, I went and flung the kite for about an hour when it got really cold back home.

So do you make custom kites? Is there a mitochondria kite that you fly? Actually, that's something I would like to do. I have not made a mitochondria kite yet, but I made mitochondria tie. I made mitochondria scarf when I organized conferences. I think that is awesome. Well, let's dive into the scientific side. As our listeners may have guessed, you are passionate about the mitochondria. So how do you describe your work and what you study to someone who's outside of your field or perhaps outside of science altogether?

So we all know when we age, we lose energy. And my goal is to re-energize people and in doing so, undo aging. And that's where we come in in terms of the tools and technology and the ideas and the concept and the hypothesis we have developed. But in essence, I would say, you know, our goal and continue research is on how to undo aging. Well, and as many of our listeners out there who've taken a cell biology course know, there's this sort of mantra from cell biology,

Mitochondria is the powerhouse of the cell. So how did the mitochondria fit into the story of aging? So there are about nine hallmarks, although they've added a few more. And what we showed over, I would say, 20 years of work in our laboratory, that mitochondria connects to all of the hallmarks of aging. For example, our laboratory was the first one to show

that mitochondria connects to epigenetic regulation. Be sure it leads to genomic instability. Be sure that it leads to intercellular communication problem and many other aspects. So for us, the mitochondria is the root cause of the aging. And as I mentioned, one cannot deny the fact as we age, we lose an energy over time. But that's not to say its only function is energy.

In our laboratory and others have also shown that mitochondria are involved in many different functions, cellular functions. For example, it is involved in immune response. So there are more to mitochondria, but the energy part is very well established. And another aspect, you know, continue to being established or they already found new aspects of function of mitochondria.

Keshav, this is fascinating. I'm excited to talk more about your research as we go through our interview today. But I'd love to talk a little bit about motivation first. I think as a scientist, it can be difficult sometimes to stay motivated and inspired to go in every day and do your best work. But do you have a favorite quote or a saying or something that just really motivates and inspires you? So I have one actually, which is from Alfred Nobel. He said he

if I have a thousand ideas and only one turns out to be good, I'm satisfied. And that gets me going because one idea doesn't work, one experiment fail. Well, what do you do? You try the next one. And on the bad days, I have one, Winston Churchill said, if you are going through hell, keep going. So,

If they're really down and think that, you know, this is a hellish day today, nothing worked, or we keep going. That's what I live on. Well, I think these are both fantastic motivational quotes, and I think particularly helpful to get you through those dark days, just remembering that you just need one good idea to have a huge impact in science and

You just keep on pushing forward despite all these challenges and barriers that you may face. So let's talk about these people who might have motivated you or inspired you. You mentioned these two inspirational figures with the quotes that you cited there. Do you have other role models or mentors or people who you've looked up to over the years who helped you get to where you are today?

Actually, it was my brother. He was 10 years older than me and I saw how hard he worked and how he ran through some of these ideas and some of them actually he translated. For example, when I was in, I think it was higher secondary, he had the idea how he can use cow dung to make electricity.

And in fact, in master's degree, I turned out that I made from cow dung to methane. And he actually lit up a village in India. And his motivation, his desire to work hard to translate and make things happen, actually, even today, continue to inspire me. And unfortunately, he passed away several years ago. Also, it was personal. I was watching him do that. So that had stayed with me.

Absolutely. Well, I'm so sorry for your loss. It sounds like this brother was a wonderful figure for you from the very early days of starting to get excited about science. And I'm curious to hear about your scientific beginnings. Can you maybe tell us a little bit more about those very early days when perhaps you and your brother were starting to explore science together? Believe it or not, when I was in school, I was fascinated with many things related to science. So I used to write Children's Corner in a newspaper.

in my high school days. And every time I read here and there, and those days there was no internet, so my brother used to get this science reporter magazine. And in that, I used to find scientific facts and ideas which I thought people should know. So I wrote about, for example, carnivorous plants in my school days.

And then I got to college and I wrote about other things like nitrogen fixing bacteria and thermophilic bacteria which survive at 250 degrees Celsius.

And then I realized, well, when you do all that, especially when you write for a newspaper, they used to give me 250 rupees for an article. I said, well, this is even better because you're not only getting published and learning new things, you also got some pocket money. It sounds like you were science blogging before it was even cool. I love that. I think so. And that got me interested, obviously, in science. And then I can tell you more about what my journey was.

Yeah, let's talk about that journey. How did you go from dabbling in scientific writing to starting to think about it more seriously as a career?

So actually, I didn't think of science as a career, to be honest. So when I was in college and my family being an Indian family and parents are expecting a lot from the children. So my brother was an engineer. He did PhD in electrical engineering. My sister did electronics engineering and my own other sister did drawing and painting, the fresco. So one thing was I was actually persuaded by my parents, well, go become a doctor. And I failed.

I sat for their entrance test, which is very competitive in India. And I did not get in. Then I was let free. And then my father said, my mother said, well, you go whatever you want to do, but get out of the house. So I, at the time after undergraduate, I said, okay, what can I do? So I applied for horticulture science, plant breeding, microbiology, biochemistry. Think of anything. When I see the admissions, the universities that are tied in the newspapers,

I apply and I got in some of them. And what turned out to be that microbiology appealed to me quite significantly because at the time, one, there were only six seeds in India. So it's very competitive. And then I also read about these methanogenic bacteria, which Ralph Wolf in the United States helped me to do my thesis. So I used the cow dung in my thesis to make methane. And it was these bacteria are very difficult to grow.

They're strictly anaerobic. So even the trace of oxygen can basically kill the bacteria. You can't do anything else. So I wrote to Ralph Wolf, whom actually I met later on after finishing my PhD. I came to Woodsall and he was so generous. He sent me his hungate tube, which are different types of tube, different type of conditions you create. When I got that growing, I made methane. And then I was very proud to tell my brother, well, now you can do whatever you want to do to make electricity.

And then fast forward after doing my master's degree, I took a pass and I thought, okay, I do PhD in India. And I applied for many institutions. Some of them are very top institutions like IIT, which is Indian Institute of Technology, like MIT. But my problem at the time was that I did not speak English well. I came from a village where we have our mother tongue, then we had to speak Hindi.

Then the state language was Urdu, which is like Arabic. And I had Sanskrit, which we had to study. So English was only that you translate. It takes time to translate, to communicate. But while all this was happening, I got a PhD admission in Australia.

And you can imagine then I said, well, I'm going there. Time to learn. Yep. And that's where I learned English. And believe me, Australian English is different. I can give you some example later on, but I could not understand. So I went through the English classes for about three months and still couldn't understand very well. They have so many slangs that it was very difficult. So what I used to do is I know what they're going to ask you on Monday. How was your weekend?

So I already prepared my answer. And sometimes they ask you something spontaneous while I'm thinking, they will walk away. They thought, well, this guy doesn't understand what they said. Or to be honest, he's not even an idiot. But I learned my way. That phase changed because during my PhD, I came to Woods Hole. So I was doing my PhD in marine biology at the time. And I was fascinated with what goes on at Woods Hole research-wise. And I got this scholarship and

When I came to Woodsville, I realized, oh, well, I can understand English very well. It's just that it happens to be Australian English, which I can't understand. That made a big difference because I was sort of losing my confidence.

Because when you're spontaneously communicating, you need quick thinking. In early days, I was translating from my mother tongue to Hindi, then to English. And just that vocabulary, I think, like you said, there's certain words that they use in Australia that they may not use in American English, and it's complicated. So it sounds like this trip to Woods Hole was a transformative experience and important on your journey because it, like you said, gave you this boost of confidence. What then did you think about as you were graduating with your PhD and trying to plan your next steps?

So that was actually a turning point in my career, my life, because when I came to Woodsoll, believe me, it was a festival of science.

I'm not sure whether many people have been there in Marine Biology Laboratory. So we were in the dorm. We work, we play, we have fun. That's where I actually had a lot of fun flying the kite because you were right on the beach. It's a private beach. And you can go and do the experiment any time of the day or night. And the library actually was open 24-7. And I was told that it was open since actually 1800, something when the Woods Hole was formed. And then I realized, you know what, I think this is a place I want to come back.

So I came here, Woods Hole, for about three months, but I loved it so much that I stayed longer. And in fact, we discovered a bacteria which is unique. And in fact, we named it after me and my professor. We call it KE for me and WA for Walter. We published it and it was really fantastic in terms of what we discovered. So I went back to finish my PhD as fast as I can. Then I came back as a postdoc at Harvard.

And this journey continues because I realized that this is really, you know, science is fun. Definitely. And I know it was some time ago, but then as you were finishing up your postdoc there at Harvard, you started looking for faculty positions and you landed at Johns Hopkins University. Can you talk about that transition?

So when I was at Harvard, I had a deadline for my scholarship, which was finishing. And those days they had just begun talking about 1995. And I was applying for jobs and I wasn't getting anywhere. Believe me, anywhere. So I can tell you.

When I stopped counting for jobs, that was 770 jobs I'd applied. Oh, my goodness. So I bought an Apple computer and a printer. I will put kids to bed and then I will look back in the back of science and what is advertised. So I can tell you those 770 jobs in universities I apply. When I drive along the United States, I can tell which next university is coming.

because I applied to all of them, St. John's University to Western Kentucky to anywhere I can find. And I don't know why I wasn't getting any interview or anything. But then it turned out that I think my fellowship was ending in March. I got a interview in November, December from Hopkins. But one good thing was I was not afraid to apply for a bigger school because I'm applying. So whatever happens, happens.

And after three consecutive interviews, and actually what I'm doing today in last 25 years is what I had talked about at Johns Hopkins about mitochondria. Because there were many candidates, then there were three candidates, then there became five candidates. They wanted to out-compete each other. So they came up with the idea that, well, you tell us three projects you want to do and how you want to raise your 90% of salary. They

because it's a private institution within three years. So those projects I wrote, actually, one of them, I'm still continuing on it. That's remarkable. And obviously, the interview went well. You were able to land that position at Johns Hopkins School of Medicine right in the nick of time, it sounds like, before that postdoc fellowship ran out. And then later on in your career, though, you made a move to the Roswell Park Comprehensive Cancer Center. Can

Can you talk about what led to that change? So let me tell a little bit more about Hopkins and I'll get back to Roswell. So when I came to Hopkins, yeah, I got hired. I felt good about it. First time in my life, I had a laboratory and an office. So when I finished my postdoc at Harvard, the idea was that, well, now that you're going to be competing with us, you find your own way, find your own project.

So at Harvard, I was working on DNA damage repair. And for me, it was, well, there is another DNA in mitochondria, and I'm just going to work on that. And that was actually a turning point in my entire life. And that's why I want to talk about it a little bit. So there was a Lenin's protege, Pete Pedersen,

a professor in biochemistry department. And I was looking for a mentor because he never had a mentor. So I thought, well, just go to him. And he was part of the committee and asked him, I want to work on mitochondria. And he said, everything what we need to know about mitochondria, mitochondria produces energy, as I mentioned in the beginning of my conversation. And

And he said, you're going to be wasting your time. There's nothing more to it. So I got really depressed for a while. So there was a Warburg effect at the time that cancer cells have defective mitochondria. So I dwelt on it. Then I said, I don't know what, I got to sail my own canoe. And that really was changed my life. So before I published a paper, because I was not able to get published easily at the time. So I wrote a book on mitochondria.

And during that process, I found actually a gold mine. So there are set of mitochondrial diseases. The primary defect is mitochondria and

And there is one in 2,000 children born in the United States developed that disease. There's absolutely no treatment even today. And it takes 14 doctors to diagnose. When I discovered all of that writing the book, I said, OK, I need to do more. It's quite funny. So I used to talk to my children on this when you get depressed. And my daughter said, I think, I don't know, it's not worth it. So I said, I'm going to write a book. And she said, who's going to read it? So I sent a table of content to one publisher and...

And within, I think, a half an hour, he said, oh, well, it's a deal. You go ahead. And I was naive. I didn't care about what percentage of copyright, all that. So I wrote the book. And then he said, what's next? So I talked to the family and said, oh, no, I'm going to start a journal called Mitochondrion. So I put that idea out there. And in fact, there was Elsevier and many other. So I started the journal. And I said, well, what's next? Because this is a real human problem. So...

I thought, okay, let's start a society for mitochondrial research and medicine and bring doctors, scientists, engineers, and patients and everybody together to focus on this problem. And that's what I love about the United States. So we instituted the society. And after that, people competed around the world. And I was just really pretty delighted to help them get started. So in Japan, Korea, Taiwan, China, India, and we still continue on that aspect.

So that was what happened at Hopkins. And the turning point was I left Hopkins because there was a very well-known family whose son was affected with the illness. And he showed up in Wilmer Eye Institute and Dean called me and said, well, these are things you do. You should help. So I helped get the diagnosis. And then the thing was, well, we will get something more.

in terms of your needs and all of that. That did not happen. So after that, I went to Hopkins Dean and the president's all the time to open for Center for Mitochondrial Medicine, because that's where this is going to go. That didn't work out. Then I moved to Roswell Park. And the reason I moved to Roswell Park, because there used to be a scientist, Dr. Dougherty, what he accidentally discovered is photodynamic therapy.

And what that does is that photodermal therapy is driven by singlet oxygen through mitochondria. So that type of photodermal therapy still works very well for certain types of cancer. So basically you give this compound, it finds its way on the mitochondria and the tumor, and then all you do is light up the tumor and cells die and the tumor dies.

That got me interested when I heard and they were looking for someone to work on the mitochondria. I appreciate you going into some of the detail because I think you have a very interesting story. And then we obviously mentioned in the introduction now that you are there at the University of Alabama at Birmingham. Can you talk about how you decided to move to the University of Alabama?

So I got a call from Cancer Center Director, Dr. Patris. To be honest, I did not know much about Alabama or this part because I lived mostly in Northeast. And he invited me to give a talk. So I said, okay, I come down and we'll invite you to go and give a talk. And about two hours in my visit, he

He said, well, there is a position here and I hope you're interested and let us know. So I gave my dog and I had a wonderful trip here in Birmingham. And one thing about Birmingham is people from outside do not know. Birmingham is a very nice place. It's got Appalachian mountains. You can choose the lifestyle you want. But from outside, given all the history behind it,

People just don't appreciate it. So I went back and talked to my family. And at the time, you know, it was Buffalo and my kids were almost grown. So I said, well, I think it's time to get to one more place. That's how I end up here. That's fair. And you are doing remarkable research there at the University of Alabama at Birmingham. So I'd love to talk about some of your current research. So Keshav, is there a particular project that you are working on right now that you were just the most excited about and want to share with us?

Yeah. So the bigger goal is to make people young again. So the idea is that when you're young, I take your young mitochondria and give you back when you're old. The energy decline I'm talking about energizes you again. So that's a very large goal and a long-term goal. But we are looking at many different ways what we can learn about mitochondria transfer technology.

and develop technologies. So in fact, let me back up a little bit. So in 2007, 2009, and around that time, I had the idea that we can transfer mitochondria, thinking on these lines, what I've just described to you. So we took the mouse mitochondria and we emptied out a human cell line, which didn't have the mitochondrial DNA. And it's okay, let's put it together in a test tube and see whether the mitochondria gets in the cell. And

there is a mouse we deliberately use mouse because then they can genetically track it so by diffusion the cells took it and then I tried to publish didn't get any traction you

We went around from one journal to another. Eventually, we published in Rejuvenation Research. And I thought, wow, this is really exciting. I should continue on it. And then we published another paper where we took the African-American mitochondria, where these women have very aggressive breast cancer when they're young, and transferred their mitochondria from platelet and recapitulate in mice that happens. Then we did other experiments where we took from tumor mitochondria. But

But none of that got traction. We had a hard time. So I moved on and said, OK, that's about it because you have to remain funded to do science. And then a few years later, I made some groups in Taiwan and I learned that a group at Harvard was transferring mitochondria from his skeletal muscles and doing injection in the artery that these children have extended life for about one to two because they were terminally sick.

Anyway, so we put together and it's okay, let's get going. Then last year was a meeting in Chile, where I see some of the other part of the world, I think they are more inclined to accept these new things. There I learned that, well, more so than before, that this field is moving, but moving in a very wrong direction because there's no controls, there's no standards.

standard practice and nothing. So I put together a team of 31 scientists around the world in 13 countries, four continents, and almost for a year last year, we worked together and we got a consensus paper, an idea and what to call and what to do in nature metabolism. Now there is a lot more interest. So that is why I described to, we are hung up about it now. So hopefully I

It will have traction this time than about, I would say, 19 years ago. But I truly believe that the mitochondria banking, or just like the biobanking, if we do it right, we may not completely rejuvenate and get to a young stage, but we could certainly get benefits.

Definitely. And I think there is just such an interest in this movement to sort of be young longer, have this longer health span. So establishing these guidelines, these norms within the field is critically important to get everybody on the same page to make sure we can all understand each other between, like you mentioned, these scientists across all these different countries who are working on things relevant for this particular field.

Yeah. In fact, we are writing at the moment, as I speak, an article for Nature Communication to basically talk about what technology needs to develop in this area. For example, when you transfer mitochondria, we do not know its biodistribution. So if I take mitochondria and put it, say, in the skin, I do not know whether it goes to heart, goes to lung, and how long it stays, when it gets degraded, what happens in the cells.

So we are also taking actually one technological approach, what needs to be done. Then we are using a model organism like Baker's yeast. In fact, it was the first paper, which actually is in the article. Somebody did this experiment and probably forgot about it in 1979.

They transfer mitochondria from the yeast to another yeast. So we are going back and say, okay, I think that could be a faster way because yeast grow faster and you can manipulate genetically, not like mice or other systems.

I think that's so cool. I think learning from some of this classical literature that sometimes goes forgotten for a number of years is a really good source of inspiration now that you have some of the instruments that you can move the field forward with. And to move the field forward, you also need to have the right tools and supplies in your own lab. And we'd like to take a moment to thank our sponsor, Innovative Research, and to talk about their portfolio of human biological products. Innovative Research is well known for their human whole blood plasma and serum, but

but they also supply other human biologicals and matrices such as saliva, tears, sweat, and urine. Available donations from FDA-approved collection centers range from healthy adults to samples from individuals with specific diseases. Contact them via email at sales at inov-research.com. That's sales at inov-research.com to find out how they can provide human biologicals for your research study today.

And returning to our conversation with Keshav, now we talked about through your scientific journey, some of these challenges, some of these struggles that you face. And I think it's important to talk about these difficult days in science because so often the public only sees this really shiny result at the end. So Keshav, do you have a favorite story of a failure or overcoming a challenge that you could share with us today? So one obviously was at Hopkins. I almost failed there because I

I wrote the book. He started the journal. He started the Society for Mitochondrial Research. And nobody can tell you, any mentor will tell you when he's starting a career, you do this. You do this in reverse. When you get to full professor or now chair, then you write a book. Then you do all of this thing. So for me, that was survival. And at the time, my clock was ticking. I had three years. And in two years and nine months, I got a real breakthrough.

Because I was down, I said, okay, I can do all of this, but that doesn't keep me in the job because you can do all this intellectual thing, but if you don't have the funding to support 90% of salary...

And actually those days they did not have Google, they had Netscape. So what I was doing is when we incorporated the Society for Mitochondrial Research in Medicine, I learned HTML to make websites and things. So me and my children will, you know, get together, we will get the patient picture, put it all together. But one night I was just doing search on Netscape. I don't think many of your ideas will know what Netscape is. Sound like I'm a dinosaur, but I did a search on Netscape and turned out there was a

picture of a house and it says Elsa Pardi Foundation. And it's only one page in an old house somewhere in Michigan. And it's a fun research and it's just had a P.O. Box number. And I said, wow. So nobody buying what I was trying to do at the time. And at the time we were doing something simple. We were doing that mitochondria have DNA repair mechanism. So like nuclear DNA have repair system. I was proposing

The mitochondria also repair their DNA. But people were saying, well, there's no need to repair. You have so many mitochondria. So you get rid of mitochondria, produce new one. The repair people were saying, well, not needed.

And that was based on an article published by David Clayton in 1979, I believe, that there is no repair mechanism for nucleotide excision. So UV-induced lesions are not repaired in mitochondria. And that is still true. So having all this background, I said, okay, I've done all this. I don't have money. So I wrote to Elsa Pardi Foundation, just a two-page grant of my idea, what I want to do.

And you would not believe, I think I got, after a month or six weeks later, I got a $208,034 check in the mail, which I did not believe.

Because my daughter in particularly, she was pretty cheeky to get me going. She will write a check like $5 and a fake check and send me at work. Oh my goodness. And the interesting part of that, the check came in the ordinary mail directed to me. And there was nothing like a letter saying you being funded and all. So I literally tore it to part two in the garbage. So I talked to my daughter and said, well, don't do it.

It's very depressing. And you upset me, you know, sending all this thing. She said, Papa, I did not send anything to you. I promise. Then in the middle of the night, I said, oh no, maybe there was something I, there were parties written on it. So I probably wrote a grant. So before the cleaners come in, I went in four or five in the morning, collected that check. And then I glued it together with the tape in the bag. And it's, oh, this looks real, but I'm not, whether it's real or not. And they did not have a phone number, believe it. It's only PO box number.

So I wrote a letter to them and then they send us the award letter. That changed everything for me. And then you needed to request another copy of that check, right? Yeah, that's right. Well, that is remarkable. I have that check framed in my office because that is my motivation. They say, well, when you're ready to give up, you just don't know. Somebody somewhere, you know, could like your idea.

I think this is an amazing story of overcoming challenges and almost not believing in your success at the end was almost your biggest barrier. Well, I appreciate you sharing this difficult journey for your research, but we love to celebrate the successes as well. And we've touched on a few of them already, but do you have a favorite success story, Kashaf, about your research or your career?

So after I moved to Birmingham, and idea was, as I mentioned, that we continue to work on mitochondria. And my idea was we develop a mice where we can disrupt mitochondrial function at will. And we created that mice. And the shock we got, and later on became a really excitement and success story,

is that when we disrupted the mitochondria in these mice, in a whole animal, these mice developed wrinkled skin and lost their hair. And my assumption was because mitochondria are the powerhouse of the cell, we all know, that they will have a cardiac problem or brain problem

which they do. But the first thing within four to six weeks, what we see is massive wrinkles and a loss of hair. So I didn't believe it. So I had other people share the mice because, you know, when you're independent to study and independent verification, it's much more comforting. So whenever we did that, 100% of the mice were doing that. And the idea was, okay, so mitochondria involved in skin aging and loss of hair. So the next we thought, well, what if we can restore the mitochondrial function?

So we made this conditional knockdown of mitochondrial function. So for example, if we take away the doxycycline antibiotic, the mitochondrial function will come back. And when we did that, we got even more shock. So the wrinkle were gone and hair came back.

And I'm not a dermatologist. So I had to go back to my old textbook to study dermis, epidermis and Langerhans cells and all of that. And I also found a collaborator who can help me understand that. And that actually, when we published it, it got the attention of the world. So in New

Newsweek and Bazaar, Vogue and think of anything. And it was translated into 144 different languages. So that was good. But then I got a lot of tweets and other things and say, hey, so it's in miles. Are you going to do anything for us?

And there's one person actually I have from Israel. He actually tweets 3.30 in the morning and saying something like this. And then he said, bloody hell, I hope you do something. No pressure, right? So I said, oh, and actually the media put pressure as I'm sure we're all aware of that. When they were presenting, if you go, I can do a Google title. They were not saying it done in mice. It's only somewhere up to two paragraphs later, they will talk about mice.

Just the flashy headline. Yeah, the headline was the age reward. So as you, and there were talk shows and it was covered in news outlets and the TV. As a scientist, we often, you know, especially basic science, we think, well, we got this publication, now we let get a grant and that's enough.

But then I thought, no, I think I'm going to take. And I talked to the university and they said, well, I think you should just license it and do what you were doing. And for me, it was, no, I'm a risk taker. So I said, well, I'm going to start something new. And at the time, there were people who contacted me and turned out my current CEO, Greg Smurgle, he's in Boston. He contacted me on LinkedIn and

we got together, we started a startup called UR Biosciences. UR means young in Hindi. So that's the story at the time. Obviously, I had a lot to learn in terms of starting a business and I knew nothing about it. We raised $7.5 million last year. We had a product out with Bosley for hair regrowth. And both CMOs said this is the most important innovation in the last 25 years. They

And in fact, they've been very generous to me. I wrote their instruction manual and they put my name on the instruction manual. So that was for hair. Now we actually, we have done clinical trial for a skin. So we

we have very good result for basically addressing the skin wrinkle. And now we're moving into ovarian aging. And I can tell you in a minute about it because that is a huge problem as well as there's nothing out there. So for example, there is a premature ovarian syndrome or disease. So a woman under 30

35, they develop this just like menopause. All the symptoms, they don't conceive and there's absolutely nothing out there. And one in, I think, 4,000 women have that problem. And there seems to be quite significantly mitochondria are involved. In fact, I learned that mitochondria are more important for ovaries than anything. So

That stands for an article published in 2000. And actually, I wrote an editorial on it in Nature. And at that time, what they were describing, I think the technical term they use is upas. So there were a group of women who did not conceive and the fertility declaration described them as upas women.

And what this fertility clinician did was transfer the ooplasm from a 22-year-old woman and did the in vitro fertilization and used the egg in the sperm. And there were 22 children who were born around the world.

That article came to me for review. I asked them certain questions. And at the time, it didn't go further because technically there were two mothers and a father because the mitochondrial DNA came from the young woman. So things stopped. But at the time, I learned that how important mitochondria are for the ovaries. So fast forward, we are working on the ovary.

ovarian aging. And we have actually in this mouse we have developed, we have significant evidence that these mice show changes in estrous cycle as you see the menopause. It also shows a antimalarian hormone which is down-regulated just like the menopause. So we are doing lots of things in order to either protect the mitopandal function or restore the mitopandal function.

And the benefit is if you can delay menopause one year, you'll get 10 years of health benefit of many diseases. I think that's remarkable. And Keshav, congratulations, of course, to you and your colleagues on all of these exciting discoveries that we've been talking about today. I think it's so important to take a moment to celebrate these wins because I think it's

It's all too often that you just sort of squirrel yourself back in the lab and get right on to the next question. But we try to encourage our listeners to take a break, to give their minds a break. And we recommend that everybody tries to read broadly. So we love collecting book recommendations from everybody that we feature on the show. So, Keshav, do you have a favorite book, whether it's related to science or not, that you'd like to recommend for us today? I do have one and it's to do with the science.

When I was growing up, my parents used to think reading novels is a waste of time. They want to just study and study more. You would not believe I have not read any novel, any fiction, anything. And in fact, I've written three books. So I find that while writing a book is easier than reading it. And I'm also very impatient because

If I want to read, I want to know everything in 20 minutes or maybe for less than that. So I'm not a very good reader of the books, but I have read because in the line what we're talking about is a book about the regenerative medicine, which goes back to 10,000 years ago, the book of Kaya Kalpa. So the Kaya Kalpa is a science of regeneration and described 10,000 years ago and regeneration of the whole body and mind.

And yoga is part of it. And they have some anecdotal information about because it's not rooted in modern science. So I've been reading that partly because when I get the time, I want to write a book on those line, bringing up to date knowledge and information to help the people.

And there are interesting findings already. So, for example, Dr. Salazar at Harvard, she did studies in how doing certain kind of yoga, one is Kripalu yoga, can activate the brain function. Then there are a group of people who have talked about how doing certain types of meditation can affect the mitochondria. Directly, they have done these studies.

So I will be happy to work with anybody who wants to pitch in and we can work together to develop this project and have a really good book on regenerative medicine. And not only just the Kaya Kalpa, other cultures have this type of concepts and ideas and perhaps therapies too.

I love that. I love this idea of bringing the scientific lens to some of these traditional practices, things like yoga, mindfulness, meditation, that we're sort of just starting to enter this phase of researching and really understanding the kinds of impacts that these type of practices can have. And we touched on early in our conversation, some of the travel that you've been able to, you mentioned this trip to Chile was particularly transformative. And I love talking about scientific travel because I think there are so many amazing opportunities to go to conferences and to talk to and

meet with scientists from all over the world. So Kashav, do you have a favorite place that you've been to for your science?

I've been to many places and I have a couple of favorites. Chile was one of them, actually. We went last year. I knew nothing about the people, the group and anything, but they were so welcoming that they're now like a family member and the wonderful science. And we went to Vargas and many places and it's all talking science, talking to new people, and then you become a family member.

visit their home for dinner, lunch. And in fact, we're going to have another conference like that this year in October on the same lines. And also what I really got excited about it, that that away from work gave me the idea to do something about the field in isolation or with a new group of people. You have your own time, nobody bothering you. You

write the grants, write the paper and all of that. And the other place was actually Malta, which I went last year. I met people in the plane. And when I said, oh, I'm going to Malta from Copenhagen. And the person right next to my seat was saying, well, we are moving there.

And I said, why? So that actually couple told me all the good thing about Malta, which I really enjoyed it. And then I learned all these people from Denmark and other part of Europe are moving because it's also cheaper to live and good living. But again, the science was really good. And I made lots of friends and the hospitality of those people. So for example, my flight was six o'clock. So I thought four o'clock, I'll get up, take a cab. Now in that hotel,

I got down and four o'clock, they had the breakfast ready. And it's not just a breakfast, like, you know, you get donuts or bagels. No, no, there's a full-fledged breakfast in a trolley. And when I came down, this gentleman came and says, sir, I can carry your suitcase. So I said, oh, so you are working on Night Shift. And he said, I'm the manager. Oh my goodness. I mean, what more you can ask? And the other one in Austria. So in Austria, I think it's a place called Innsbruck. We landed there. It's a mountainous runway.

And then from there, the conference was in a small town in a church. The church was the venue. And I got there and

And the organizer said, here is your room. So I went in the room and I found there were two bunk beds. Exactly what you were expecting, right? Then my other colleague comes in and he said, hey, what are you doing here? And I said, well, that's my room too. So I said, well, there's another bed. So we had to negotiate who's going to sleep on the top or the bottom. Which one did you claim, Keshav? I claimed the bottom because I'm older than you. I can't climb. So then you find, you know, all these people early in the morning drinking, what's pretty interesting to watch.

That is small village. They were probably close to 800 people. And I think there were 200 people attending the conference. The organizer forgot to get a pleasure pointer. So we had to go outside to get a branch of tree. Make your own old school pointer. Yeah. So one thing I did was when I got home,

Believe me, I have a green pointer in my one bag and a red pointer in my other bag. I carry my laser pointer everywhere I go. You are always prepared. I love that. Always prepared. And I share with other people, those who don't have it. I think that is wonderful. I think these stories just showcase, like you said, this welcoming nature of the scientific community and the people that you meet along the way. And I think

That goes contrary to a lot of the stereotypes and the ways that scientists are often portrayed in the media. So we love kind of focusing on this human side of science. And I think there are so many amazing, funny, quirky people in science. So Keshav, do you have an example of maybe a quirky tradition that you've experienced or just a funny or fond memory that showcases this human side of science? So we used to go to Gordon Conferences. So the Gordon Conferences are in New Hampshire.

And New Hampshire, the bar closes 11 o'clock and people are just come dinner, they went to bar.

And you just get talking to people and then suddenly everything close, you go to your room. Well, somehow there are some people from Scotland, professors and other people, and they were very upset. That's well, what the heck we should do? One person decided that the door is not completely locked. So why don't we take the drink from here and go elsewhere and we continue the party?

And the thing was, we will make sure that whatever we were paying, we will pay. So we stayed up all night until six in the morning. We'd talk about this project, that project. Some of them obviously were, most of them were nonsensical, but some of them were really good, which I come and follow up on some of those things. That year onward, I'm forgetting his name.

Every time after that conference, he brings his own supply of drink. You've got the laser pointer. He's got the beverages covered. You guys are prepared. Exactly. Exactly. So wherever he goes, I'm pretty sure that we don't have to worry about it. We have the ideas. And he's a crystallographer. I haven't seen him for the last few years. And believe me, when people have that kind of environment, you really throw your silly ideas. And I give you one example.

So there was one conference, which is NIST, they have National Institute of Standard and Technology. So me and one of my friends, Bob Navio, we were sort of giving them advice how to develop a standard for proteomics. And our idea was, if you cannot develop a standard for proteomics of mitochondria, how could you develop for the cell and the tissue and the organ? And all this proteomic field was exploding.

and all the markers and everything. So I was sitting in the bar with Bob and we were sort of throwing here and there. And actually he's a very good friend. He makes me better every time I talk to him. And I said, you know what? We can make a super soldier.

And we started throwing all this crazy ideas and we did not realize in the same bar there was an army personnel. He was listening to our conversation and he comes to us and taps on my back and he says, "Hey, I want to hear that tomorrow morning. Can we talk? Can we set up a time?" So we set up a time, talked to him. Now we got serious. You would not believe that that idea actually took shape. DARPA actually had a special request.

And he told us that any of these ideas you have, if you put an ounce of weight on my soldiers, it's a no-go. It's a valley of death. Oh, wow. So there were some funding on that idea because...

soldiers, what happened, they carry food for a certain amount of time, then they had to be fed. And then, you know, so the idea was that you make something related to energy. And actually he was saying that I want my soldiers to fight for a week without food or supplies in the trenches where they are. So that was the story I'll never forget.

Absolutely. I think these serendipitous meetings can really change the course of maybe a research project or even the course of your career in some cases, kind of being able to tap into some of these other resources, whether it's DARPA or other opportunities. So very cool. I appreciate you sharing these human moments in science. And I think you have to have this sense of humor and this open-mindedness, I think, to tackle a lot of these big questions in science. And

Oftentimes you're limited, unfortunately, Keshav, by things like funding and staff and technology and a little thing called feasibility. But if we took those barriers away, what is the one research question that you would want to answer most?

I think at the moment is how could I protect mitochondria, sustain mitochondria and regenerate mitochondria for better health. And in that process, I will say how we can either mitigate or undo aging. And the priority for me is obviously the skin and ovarian aging at the moment.

because it is such a huge problem. And my bigger goal is with the mice, we can make the mice old and then we can make the young again. So if this mitochondria banking becomes

We can take the mitochondria at a young age and give you back and get the benefit. And these things, I'm sure NIH won't fund it. So I'm putting together kind of a pitch book. And in fact, I'm going to a two-month conference in April and May. It's called Vitalis Bay. Adam Grice is organizing it. And the idea is like having a Manhattan Project for longevity. And they bring everybody together.

If you look at retalistbay.com, it will tell you. So my goal is to basically take some of this idea and see if I can find any funder. If they are, you know, we start a new startup or work with anybody who wants to partner. Or if I can't do it, let somebody else do it.

Fantastic. Well, Kashav, I think this is so exciting. I think it's hard to wrap your head around just the possibilities in your research area. So we appreciate you giving me and our listeners a lot to think about today. And you've shared your insights along the way, but we always love to end with a piece of advice. So Kashav, is there a piece of advice that somebody gave you at some point that you can pay forward to listeners today?

Actually, I'm very much family oriented. So one piece of advice my father gave me, which I still follow, he said, fail successfully. And at the time, I didn't quite understand. But then he would say, well, basically put your best foot forward with the 100 percent. And then you can say, well, I failed successfully. I think that's wonderful advice. Is there any other last piece of advice or a last note of inspiration that you'd like to leave everybody with today?

Do what you love and love what you do. People in my laboratory, that's the first thing I ask them. If you're not interested in the project, let me know. Because if you have the passion, you can overcome a lot of hurdles. I think that's a wonderful message to share with listeners. And I think your career, your own journey is a testament to it. And if our listeners want to learn more about you and the work that you're doing, Kashaf, what is the best way for them to do so? It's easy. Mitochondria.org.

Excellent. Listeners, definitely take the time to check out that website and learn more about the amazing work that Kashav and his team is doing. And we appreciate you joining us on the show today. Kashav, it's been so wonderful to learn more about you and your work. Delighted to be here. Thank you very much for the opportunity. Absolutely. And thank you, listeners, for joining us as well. We hope you'll join us next time for another episode of People Behind the Science.