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The Role of Sirtuins in Longevity Medicine · The Science of Skin

• 0:08
  SPEAKER_01: Hello and welcome to Skin Care Confidential, the podcast supporting the Science of Skin Summit.
• 0:12
  SPEAKER_01: My name is Dr.
• 0:13
  SPEAKER_01: Ted Lane.
• 0:14
  SPEAKER_01: I am a board certified dermatologist in Austin, Texas, and your host for today.
• 0:18
  SPEAKER_01: We are actually at the Science of Skin Summit.
• 0:21
  SPEAKER_01: It's an annual educational event held in Austin.
• 0:24
  SPEAKER_01: This year, 2025, is in September.
• 0:27
  SPEAKER_01: Next year, 2026, we're going to be in September as well at the Fairmont Hotel.
• 0:32
  SPEAKER_01: My guest today is Dr.
• 0:34
  SPEAKER_01: Rishab Kala.
• 0:35
  SPEAKER_01: Rishabs, thank you so much for being here.
• 0:37
  SPEAKER_01: Thank you for having me.
• 0:38
  SPEAKER_01: So Rishhab is with Estee Lauder.
• 0:40
  SPEAKER_01: He is a lead scientist there.
• 0:42
  SPEAKER_01: As the director of the Advanced Technology Division at the Estee Lauder Companies, he leads research and development efforts focused on longevity and epigenetics.
• 0:52
  SPEAKER_01: He earned his PhD in biology from the University of Alabama at Birmingham, where his research focused on the epigenetic effects of the dietary compounds in cancer prevention and aging, which has been cited over 800 times globally.
• 1:07
  SPEAKER_01: He also went to the University of Michigan Medical School where he investigated the biological mechanism of aging in slow-aging mammals and completed specialized training in biomedical innovation and entrepreneurship.
• 1:19
  SPEAKER_01: So we certainly have the right person with us to talk about epigenetics and longevity and aging.
• 1:30
  SPEAKER_00: Yeah, it's it's all almost two years now.
• 1:32
  SPEAKER_01: Almost two years now, where you've been leading the research and development in the epigenetic and longevity space.
• 1:38
  SPEAKER_01: Well, you know, at our conference we have so much focused on regenerative and longevity, certainly in the skincare space, that is the theme of 2025, and I think for the next at least five to ten years, if not longer.
• 1:50
  SPEAKER_00: It's amazing.
• 1:51
  SPEAKER_00: I'm enjoying it.
• 1:52
  SPEAKER_00: It's very amazing.
• 1:53
  SPEAKER_01: But if you look at skincare, it what happens in skincare happens in medical dermatology just about five or ten years later.
• 2:00
  SPEAKER_01: And so really skincare is the tip of the spear and leading the scientific innovation in longevity intergenerative, but it's just going to bleed over into medical germ, and indeed it already has as we look at some of these medical germ companies that are focused on senescent cells, for example, as the initial cell of inflammatory disease.
• 2:18
  SPEAKER_01: But just to focus on your research in particular, Rishab, how do you see the longevity movement changing the conversation around aging and why did Estee Lauder start focusing on skin longevity?
• 2:30
  SPEAKER_00: That's a very good question.
• 2:31
  SPEAKER_00: Like you mentioned, the healthcare first leads the space and then skin care follows that, and then medical skincare goes into that.
• 2:38
  SPEAKER_00: So the entire conversation around longevity, uh skin is one of the major organs, right?
• 2:44
  SPEAKER_00: It is the largest organ in our body.
• 2:46
  SPEAKER_00: So it has to be part of the conversation.
• 2:48
  SPEAKER_00: So anything related to longevity, skin has to be a main place.
• 2:52
  SPEAKER_00: It holds a main place in those conversations.
• 2:55
  SPEAKER_00: For Estel order, this all started in 2008.
• 2:59
  SPEAKER_00: Um after completion of the Human Genome Project in 2003, when scientists were trying to figure out like, could genetics be the answer to all the diseases?
• 3:08
  SPEAKER_00: It turns out that's not true.
• 3:10
  SPEAKER_00: It's the lifestyle and environment which plays a very key role.
• 3:13
  SPEAKER_00: And that's where the term epigenetics came into place.
• 3:17
  SPEAKER_00: And this is where you have the ability to turn on and off your genes depending on your lifestyle, depending on the uh way you live your life or the social connections you have.
• 3:28
  SPEAKER_00: And in 2008, we we started our collaboration with Dr.
• 3:32
  SPEAKER_00: Leonard Garente, uh MIT professor, who was doing some groundbreaking work on sertments.
• 3:38
  SPEAKER_00: Uh, these are the longevity proteins.
• 3:40
  SPEAKER_00: He was overexpressing them in model organisms, and what he saw that it was improving their health span and lifespan.
• 3:46
  SPEAKER_00: So, what we thought was like, why can't we take that research and bring it to skincare?
• 3:51
  SPEAKER_00: And that's where in 2009, uh Estel Order, we launched our first longevity platform.
• 3:57
  SPEAKER_00: And since then, till now, we have over 40 plus patent on this technology.
• 4:02
  SPEAKER_00: We have presented about our Certwin work in 25 plus conferences, we have published work in 15 plus journals, and um we are very excited.
• 4:12
  SPEAKER_00: Like it's it's an amazing journey taking something from lab and translating that for our customers to experience that uh changes in the longevity.
• 4:23
  SPEAKER_01: So from 2009 to 2025, I mean that's nearly decades of work on SERTUINs and how they are incorporated into your into the different skincare lines of Estee Lauder, Renutriev in particular.
• 4:37
  SPEAKER_01: Uh, but but so much data has been produced regarding the use of sertuins in skincare.
• 4:43
  SPEAKER_01: But it all was inspired by one professor in his lab.
• 4:47
  SPEAKER_00: He is the founding father of Certuan Biologies.
• 4:50
  SPEAKER_00: That's how he started working on CERTWIN, and we were we were fortunate to collaborate with him, publish with him way in 2008 about this whole field.
• 4:58
  SPEAKER_01: Well, let's dive into it.
• 4:59
  SPEAKER_01: So, what are sertuins and how are they active?
• 5:02
  SPEAKER_00: So, sirtuins in in a general ballpark, we call them longevity proteins.
• 5:07
  SPEAKER_00: They are evolutionary conserved from yeast all the way to humans.
• 5:11
  SPEAKER_00: If you look at centenarians, they have high expression of sirtuins.
• 5:15
  SPEAKER_00: If you look at bowhead whales, which live around 200 plus years, they have high expression of sertuins.
• 5:21
  SPEAKER_00: And if you look at a lap space like mammalian species, like naked mole mice, they have high expression of sertuins.
• 5:27
  SPEAKER_00: So clearly these sertuins play a very important role in this field in improving your health span, improving your lifespan.
• 5:34
  SPEAKER_00: And that's where we were like very much fascinated about this.
• 5:37
  SPEAKER_00: So we wanted to study sirtuins in skin cells, and this and what we found was there were seven different types of sertuins in skin cells.
• 5:46
  SPEAKER_00: Um, each were located in different locations in the skin cells.
• 5:50
  SPEAKER_00: They play a specific role in skin cells.
• 5:52
  SPEAKER_00: For example, CERT1, present in nucleus, it does a lot of repair and renew of the skin cells.
• 5:58
  SPEAKER_00: SERT2, which plays a key role in maintaining the shape of the skin cells.
• 6:03
  SPEAKER_00: For example, when a skin cell ages, it becomes more circular.
• 6:07
  SPEAKER_00: Versus a young skin cell is more elongated, it's like more connected to the collagen fibers, and that's where CERT 2 plays a key role.
• 6:14
  SPEAKER_00: SERT 3, 4, and 5, these are the mitochondrial certain things.
• 6:18
  SPEAKER_00: They really boost the powerhouse of the skin cell.
• 6:21
  SPEAKER_00: And you really need that.
• 6:22
  SPEAKER_00: And it's it has been documented that when skin cell ages, you see a decline in mitochondrial function.
• 6:28
  SPEAKER_00: That's one of the major hallmarks.
• 6:30
  SPEAKER_00: And we know our research has shown that we can reverse that to a younger phenotype.
• 6:35
  SPEAKER_00: And CERT 6, which is another major certifies, which plays a role in telomer's maintenance, inflammation, senescence, all the saps which are produced.
• 6:45
  SPEAKER_00: Now, one thing which we have to note is these sertuins respond to exposones.
• 6:51
  SPEAKER_00: And when a skin cell is exposed to UV or exposed to like DPM, even stress, you see a significant decline in certuvines.
• 6:59
  SPEAKER_00: And our data has shown that they go dormant, they really vanish from the aged skin cells.
• 7:04
  SPEAKER_00: So our our what we what we are trying to do is we are trying to reawaken this lost sirtuins.
• 7:11
  SPEAKER_00: And that's how that's 17 years of work.
• 7:14
  SPEAKER_00: We have enough evidence in lab to show that skin cells, when used in this particular format, we can reactivate or reboost the lost sirtuins.
• 7:24
  SPEAKER_01: That is so interesting.
• 7:25
  SPEAKER_01: I mean, that was just a primer on sirtuin science right there, and the importance of sirtuins.
• 7:30
  SPEAKER_01: So you could almost think of sirtuins as a marker of a healthy young cell.
• 7:33
  SPEAKER_01: That is true.
• 7:34
  SPEAKER_01: And so you you mentioned something that I think I'd just like to highlight, which is the effect of the sir, the I think you mentioned three or four sirtuins that are so important for mitochondrial health.
• 7:43
  SPEAKER_01: Yeah.
• 7:43
  SPEAKER_01: And if we think about longevity, and one of the main targets uh for enhancing longevity and health span, improving ATP production and the use of ATP by the mitochondria, which are the engines of our cells, is a very simple way of thinking, how do I improve my longevity?
• 8:01
  SPEAKER_01: I need to improve the production and use of ATP in my mitochondria, right?
• 8:05
  SPEAKER_01: That is still.
• 8:39
  SPEAKER_00: So so in a in a ballpark, certivity LP is what?
• 8:42
  SPEAKER_00: We are not adding certuins, we are actually helping skin cells to produce that longevity protein, which goes missing as we age or when we expose skin cells to different exposomes.
• 8:52
  SPEAKER_00: So that's the uniqueness of this technology.
• 8:54
  SPEAKER_00: We are helping skin cells to produce their own longevity protein.
• 8:58
  SPEAKER_00: Now, what differentiates us from the others is if you look at the longevity space, it's based on three pillars.
• 9:04
  SPEAKER_00: One is sertuance, other one is AMPK, and Tor signal, which is very famous in the longevity space.
• 9:09
  SPEAKER_01: Right.
• 9:10
  SPEAKER_01: Tor cell, MTOR, mammalian, target of rapamycin, yes.
• 9:13
  SPEAKER_00: But if you if you take a step back, mTOR and AMPK, these are important players in longevity.
• 9:19
  SPEAKER_00: They play a role in nutrient sensing, they play a role in cell growth, but they never go missing in old cells.
• 9:25
  SPEAKER_00: They're always there.
• 9:26
  SPEAKER_00: They're just dysfunction or they're humming in the background.
• 9:29
  SPEAKER_00: What happens with CERTWIN, which is the third pillar of this whole longevity uh platform, is they just go vanish.
• 9:36
  SPEAKER_00: And our research has been focused on restructure or re-reactivating this or putting that Certwin back where it was missing so that a young old cell behaves like a young.
• 9:50
  SPEAKER_00: And our our technology has shown that when we take the old cell, when we use our LP technology, we can functionally make them younger.
• 9:59
  SPEAKER_01: You know, I when I'm I'm listening to you, and it this really, I mean, we've been talking about longevity, but we're also harnessing the cell's ability to repair and renew itself, which is regenerative.
• 10:10
  SPEAKER_00: Yeah.
• 10:10
  SPEAKER_01: So we're targeting both regenerative aspects and longevity with this technology, which really does make it unique.
• 10:17
  SPEAKER_01: I'm not aware of any other Sirtuan activating technology out there.
• 10:21
  SPEAKER_01: I'm sure there is, I'm just not aware of it, but this is really compelling.
• 10:25
  SPEAKER_01: Um, as you look towards the future of longevity-focused skincare, what excites you the most?
• 10:31
  SPEAKER_00: I think uh we are seeing a big paradigm shift here.
• 10:34
  SPEAKER_00: Like earlier, if you look at cosmetics in general, it was all about improving line centrals, but now consumers are more educated, they want to understand what is the mechanism, why is this happening to them?
• 10:45
  SPEAKER_00: And they really don't want to work on repair anymore.
• 10:48
  SPEAKER_00: They want to proactively stop that from happening.
• 10:51
  SPEAKER_00: That's how you will see a big change in this whole space.
• 10:54
  SPEAKER_00: We are also like collaborating with experts like Stanford Center on Longevity, where we are trying to understand aging or whole aging in a holistic way, how lifestyle impacts it, social connection.
• 11:07
  SPEAKER_00: It's a new, newly added uh hallmarks of aging, like how it is impacting your perseverance of uh aging.
• 11:14
  SPEAKER_00: And then we also collaborated or collaborate with experts like Denika Chen from UC Berkeley, where we are trying to understand the impact of certain metabolism on skin aging.
• 11:23
  SPEAKER_00: And so I I see a very big shift from just talking about lines and wrinkles to more of uh hallmarks of aging, mechanism of action, how to prevent that from happening.
• 11:34
  SPEAKER_00: Like the there is a big shift from that, from perception.
• 11:38
  SPEAKER_01: Rishab, I'm just I'm nodding because I just had a conversation with the skincare company talking about endpoints in clinical trials.
• 11:45
  SPEAKER_00: Yes.
• 11:45
  SPEAKER_01: And how with a longevity andor regenerative space, we need to stop just looking at clinical endpoints, find lines, wrinkles, salamus, radiance, hydration.
• 11:53
  SPEAKER_01: There are so many more sub- you know, mic mic molecular, epigenetic, cellular hallmark uh endpoints that we really need to be using.
• 12:03
  SPEAKER_01: And I think that's what you're talking about.
• 12:05
  SPEAKER_01: I'm I'm wholly on board with that.
• 12:07
  SPEAKER_01: Uh, and and I think that's where we need to push all of skincare to move towards.
• 12:11
  SPEAKER_01: But otherwise, this has been incredible, Rashab.
• 12:13
  SPEAKER_01: Thank you so much.
• 12:14
  SPEAKER_00: Yeah, no, it was it was a pleasure to really share the circle in science with you.
• 12:18
  SPEAKER_01: Uh Rashab here is a is is head of of the uh the division of of advanced technology at STA Lauder, and he leads the research.
• 12:27
  SPEAKER_01: And then so you couldn't be a better person for us to talk to you about this.
• 12:30
  SPEAKER_01: Um, my name is Dr.
• 12:31
  SPEAKER_01: Ted Lane.
• 12:32
  SPEAKER_01: You've been listening to Skincare Confidential.
• 12:33
  SPEAKER_01: If you like this episode, please you know give us a like uh on the on the uh the platform that you're listening to.
• 12:40
  SPEAKER_01: Please also subscribe to uh Skincare Confidential and let your friends know as well.
• 12:44
  SPEAKER_01: We're really trying to spread the word of the science of the skin here.
• 12:48
  SPEAKER_01: Uh and this kind of platform and this podcast helps to do that.
• 12:52
  SPEAKER_01: Thank you so much, Rashad.
• 12:53
  SPEAKER_01: Thank you again.
• 12:54
  SPEAKER_01: Thank you.