AI transcript
0:00:07 American health care is in crisis we have a path to preventing disease it
0:00:12 isn’t reversing aging it’s just preventing the age-related morbidities
0:00:16 of the big three if we can keep people healthier healthier people would be much
0:00:22 less expensive seven years more of healthspan free of the major three
0:00:27 diseases seven years who wouldn’t take seven years there’s just billions of
0:00:33 data points for each person there should be a reboot new standard of care based on
0:00:41 intelligent partitioning of risk we have to do better the human obsession with
0:00:46 living longer is as old as time but in the last 20 years we have learned so much
0:00:51 more about human health and biology so what do we know today about what makes
0:00:56 humans live longer and do we have real evidence that longevity is an attackable
0:01:01 target today you’ll get to hear a 16th general partner vj ponday in conversation
0:01:06 with eric topol who recently released his new book super agers an evidence-based
0:01:11 approach to longevity eric is among other things the founder and director of the
0:01:16 scripps research translational institute he’s also published over 1200 peer-reviewed
0:01:21 articles with more than 300,000 citations making him one of the 10 most cited
0:01:26 investigators in medicine that resume puts eric in a perfect position to write this book
0:01:31 teasing the signal out from all the noise around health in 2025 one of those inputs
0:01:37 was the welderly group that eric studied which was a study of 1400 people 80 plus who
0:01:42 had never developed a chronic illness for comparison according to eric’s book among
0:01:49 those 65 plus 80 percent have two or more chronic diseases and 23 percent have three or more well
0:01:55 about seven percent have five or more and again that was the 65 plus group versus the welderly
0:02:02 group of 80 plus so what do we know about these quote super agers people who not only have a
0:02:07 longer lifespan but a longer health span is it genetics or human agency and do technologies
0:02:13 like ai glp ones gene therapies or the ability to understand organ clocks meaningfully change that
0:02:20 equation for the masses if so what difficult decisions do we have to make to rewrite the system today let’s
0:02:28 find out as a reminder the content here is for informational purposes only should not be taken
0:02:33 as legal business tax or investment advice or be used to evaluate any investment or security and is
0:02:39 not directed at any investors or potential investors in any a16z fund please note that a16z and its affiliates
0:02:44 may also maintain investments in the companies discussed in this podcast for more details including a link
0:02:49 to our investments please see a16z.com forward slash disclosures
0:03:00 my joy to welcome dr eric topol to the podcast eric thanks so much for joining us i’m glad to be here
0:03:08 so you’ve written this really exciting book super agers and evidence-based path to longevity and i think
0:03:13 it’s a very timely topic and i was curious for you to maybe set the stage for why you want to write it
0:03:18 and how you see it in the context of other books that have been coming out recently as well yeah there
0:03:25 were a few things that came together we had done a big study we called the welderly where we basically
0:03:32 found very little in the genomes of people who had gone to the age of 87 on average with never having
0:03:39 had an age-related disease so that was of course one thing that was part of it the second was i got inspired
0:03:47 by a patient i saw recently who was 98 and had never been sick and so never been sick yeah her name
0:03:55 is lee rissall and her relatives had died in their 50s and 60s that’s her parents her uncles and aunts
0:04:02 she was the outlier and say why and then there were the books that came out i had patients coming to me
0:04:07 you know they wanted me to write a prescription for apple my sin or order a total body mri said wait we
0:04:13 got to get the story straight so these three things together were the impetus that why don’t i really
0:04:20 get deep into this everything we know today and then see if i could lay out some blueprints for where we can
0:04:27 go it’s coming into a world where american health care is in crisis i was curious to get your take on
0:04:33 where we are now in health care in the us and where do you think we get to yeah so there is this
0:04:39 bifurcation as i see it you could call it like the grand slam where you get reversing of aging so you
0:04:47 keep people healthier body-wide and that’s where we see all this remarkable investments in companies like
0:04:54 altos and reprogramming senolytics and a long list but they’re really focused on a monumental task which
0:05:01 hasn’t been shown in people right but rather in rodents and some of the results are striking and
0:05:07 i hope at least one if not all these are successful the other side of this is we’ve made these big strides
0:05:14 in the science of aging with all these layers of data that are using the metrics of aging and why don’t we
0:05:21 use that to prevent the age-related diseases cancer cardiovascular neurodegenerative we’ve never done
0:05:29 that in medicine to any appreciable extent and this is the opportunity because we have a path to
0:05:35 preventing disease it isn’t reversing aging it’s just preventing the age-related morbidities of the
0:05:40 big three i think that’s something that a lot of people may not realize is that the big three that you
0:05:48 mentioned cancer heart disease and alzheimer’s and dementia that they’re greatly exacerbated by age and
0:05:52 and it’s interesting because if you ever wanted to have something that could be a cure for multiple
0:05:57 diseases which would be the one the holy grails of medicine it would be understanding the biology of
0:06:03 aging where are we now in terms of things that we can use today the first and perhaps the most extraordinary
0:06:11 thing is it takes 20 years to get these diseases with rare exception you know for heart disease
0:06:18 almost all cancers and neurodegenerative they are incubating for a very long time they all have a
0:06:28 common thread of a defective immune system and inflammation underpinning they are preventable
0:06:37 variably so cardiovascular 80 90 from lifestyle and related factors modifiable factors like your ldl
0:06:43 cholesterol that kind of thing and cancer and neurodegenerative just from what we know today
0:06:50 with lifestyle factors we’re about half that can be prevented so we have some knowledge about averting these
0:06:57 diseases but we have a lot more with all these clocks and new layers of data that are really changing the
0:07:04 face of all outgrowths of understanding the biology of aging so maybe let’s double click on that so you
0:07:09 in your book outline the five dimensions of health i was wondering maybe you could walk us through them
0:07:18 yeah yeah sure so the first most important one is ai because you need that to pull all this other
0:07:24 data we’re going to talk about together this moment that is so exciting is because we have multimodal ai
0:07:29 not only large language but large reasoning models now well especially i think when you’re talking about
0:07:34 ai it’s all the things people have seen with generative ai and so on but also just the ability to
0:07:39 understand all this data yes that you’re measuring from people yeah because the other four are such big
0:07:47 domains and dimensions so the omics it includes not just gene sequence or arrays but it has all the
0:07:54 proteins all the proteomic panels that we can get which we never could get before inexpensively it
0:08:02 includes the gut microbiome metabolome and certainly epigenome or epigenetics so the omics are rich
0:08:10 we are now seeing moving in towards things like the virtual cell then there is of course cells that
0:08:16 have become a live drug where we can reset the immune system and cure autoimmune diseases like we’ve never
0:08:23 done before could you give examples of that yeah so in the last couple years we’ve seen unprecedented
0:08:31 cures i mean never had anything lupus progressive systemic sclerosis even cases of multiple sclerosis
0:08:39 dermatomyositis so basically it’s a depletion of all the b cells and when they come back
0:08:44 they have forgotten what they were attacking it’s amazing yes it’s really amazing that leads to the
0:08:49 autoimmune reaction but the bigger lesson is we have learned how to control our immune system
0:08:56 like a rheostat and we’re going to keep getting better and better as we measure our immunom but when you can do
0:09:05 that when you can quash an autoimmune disease or when you’re trying to cure a cancer by just whatever it
0:09:12 takes to keep bringing up that immune system specific to the tumor so the immune system is fundamental and
0:09:21 that also now is involving cells and vaccines so vaccines now are capable of cures of pancreatic
0:09:28 cancer kidney cancer with these personalized vaccines using the proteins of the person’s tumor yes and
0:09:34 these are in clinical trials right now yeah i mean they’re stuff like we’ve never seen and that’s just a
0:09:41 front runner of what vaccines that’s to treat cancer we’re going to be using vaccines to prevent cancer
0:09:48 again as we get older some of us especially our immune system is getting senescent and weak and a
0:09:54 vaccine before there’s any cancer before there’s anything else could prop it up we also have drugs to
0:10:01 modulate our immune system well beyond checkpoint inhibitors and so whether it’s antibody drug
0:10:08 conjugates tumor infiltrating lymphocytes and all these different ways it’s hard to imagine that in the
0:10:13 future we’re going to lose people with cancer because of being able to bring their immune system to the
0:10:20 highest level when we need it but more importantly preventing the cancer we can do that now that’s what’s exciting
0:10:26 well and so if we put all this together what does this mean for the individual like how would their
0:10:33 life change what should people be doing yeah so i call it lifestyle plus it’s a lot bigger than diet
0:10:40 sleep and exercise it’s involving you know all the environmental burdens air pollution the plastics
0:10:46 microplastics nanoplastics and forever chemicals and then there’s other things like time in nature
0:10:53 so if each of us pulled out all the stops for the lifestyle factors which is a long list that will
0:11:01 help but it’s not going to be only lifestyle factors that are the ways to prevent the big three age-related
0:11:07 diseases you know you described a large range of things from the sort of most almost sci-fi like
0:11:12 drugs that are in trials for preventing cancer to lifestyle when people think about lifestyle it’s
0:11:17 maybe a little vague in their mind for what to do how do you make that into a science or how do you
0:11:23 help people take that to the next step to bring evidence into that i go into perhaps great pains high
0:11:32 density to cite all the studies that link like for example when you have really good sleep health and deep
0:11:38 sleep what does that do to slow your brain aging or you know if you drink sugar sweetened beverages
0:11:45 what does that do to specific not just risk of type 2 diabetes but you know all-cause mortality so
0:11:55 there are very compelling sets of data about lifestyles and these key outcomes and they’re linked to healthy
0:12:00 aging i was amazed how much data is out there that can help us it’s not just like in the year when we had
0:12:07 polygenic risk scores and we just say oh your risk for alzheimer’s but we don’t know if when you’re age 56 or 96
0:12:14 so what good is that yes now we’re saying we know it’s within a couple of years between 77 and 79
0:12:20 that you’re going to have mild cognitive impairment if we don’t do these things which includes the
0:12:27 lifestyle factors and it’s much harder to get people to do all their stuff they have no specificity that’s
0:12:35 that it’s about them yeah that they can change the arc of a condition especially when it isn’t our genes the healthy
0:12:42 story about a genetic underpinning it’s just not there we studied that it’s minimal i mean maybe it’s ten percent of what
0:12:51 accounts for healthy aging most of it is in the lifestyle factors and related matters such as the immune system
0:12:57 not functioning properly too much too little well it’s generally believed that just telling someone to
0:13:03 eat better and exercise doesn’t work but what i’m hearing you say is that you have a way to do that by
0:13:09 making it very personalized yes i mean there was a finnish study that was on just polygenic risk
0:13:16 score which is rudimentary and they gave that to a large cohort and they studied whether that affected
0:13:23 their lifestyle and the results were remarkable the people who got the data stopped smoking changed
0:13:28 their diet changed their physical activity really amped it up so we know when people get data that’s
0:13:36 specific to them a large proportion much more likely to make changes now i’m not claiming that lifestyle is
0:13:43 going to be the only part of the prevention story but once you define the high risk and it’s
0:13:48 particularized to a person that’s a big part of how we’re going to succeed i could also imagine ai coming
0:13:53 into this because one of the things ai is very good at is to take a set of data and maybe you can mask
0:13:59 out the last bit so you can maybe have someone’s health records over 30 years and train on that except for
0:14:05 the last five years and see if you can predict the last five from the first 25 and once it gets really
0:14:10 good at that you can take my records and say hey look vj if you don’t do anything this is where you’re
0:14:17 going to be and we have 99 confidence on this that would be pretty chilling yeah well you’re exactly
0:14:23 right because the pinpointing here about the timing yeah is so extraordinary for example with alzheimer’s
0:14:31 since we were talking about that you get a p tau 217 it’s modifiable by lifestyle you check it again in
0:14:37 six months or a year now you have two data points and you could say with all the other data that’s
0:14:44 available when you’re going to see 18 years from now 12 years four years mild cognitive impairment
0:14:51 unless these steps are taken this was fully dependent on ai on models that can just take all
0:14:59 this data if we didn’t have the science of aging and the ai we’d be nowhere we wouldn’t be talking about
0:15:03 this today i wouldn’t have written a book yeah well it’s important for people not familiar with the term
0:15:08 of health span that’s basically not just lifespan but how long you can be healthy yeah i don’t think we
0:15:14 really want to get to some age and be demented or compromised what we’re talking about is if you
0:15:20 don’t have heart disease cancer or neurodegenerative you’re pretty darn intact you may have some achy
0:15:27 joints and other matters but those are the things that really interrupt our health span now we’re
0:15:31 talking about health care meaning something different to be preventative and we’ll talk
0:15:38 about chronic in a second how do we help make that mind shift this is perhaps the biggest point so far
0:15:44 that we’ve been discussing because in medicine and i’ve been in it for almost 40 years we don’t do
0:15:50 primary prevention the person has a heart attack and then we get all over it but for the most part
0:15:57 we don’t prevent cancer we don’t prevent alzheimer’s and neurodegenerative diseases it’s been a desire i
0:16:04 would say a fantasy for millennia yes but we are at a very different point right now we have a path to
0:16:12 prevention primary prevention not after somebody has one of these diseases and that is what is extraordinary
0:16:20 and it was all these recent advances that led to this capability and we’ve got to jump on it because
0:16:25 it’s exciting that we could actually do this well also the thing about prevention is that i’ve talked
0:16:32 to doctors who very boldly assert that prevention doesn’t work yeah and i look at them a bit confused
0:16:37 because i say well there’s been numerous examples and they’re like well name one i was like how about
0:16:42 smoking that’s the prototype we have this huge incidence of lung cancer which has just disappeared
0:16:48 now because we don’t smoke in restaurants or airplanes and so on but one of the things that i think about
0:16:53 about that movement is that while doctors played a significant role in that that was also very much
0:16:59 a cultural movement yes and so we talked about lifestyle changing people’s behaviors i think some of
0:17:04 this or much of this has to be as much cultural as medical there’s a definite cultural component and you
0:17:10 know tobacco is one of the most impressive but there’s so many others yes i think what we’ve learned
0:17:17 like for example with sleep i didn’t pay enough attention to that but with sleep when you promote your own
0:17:27 deep sleep which we tend to lose a lot as we age then you see much less dementia alzheimer’s even less
0:17:36 cardiovascular and cancer related illnesses cases and mortality sleep regularity we need to be more ritualistic
0:17:42 about it and there are many things just on sleep itself no less about physical activity about for example
0:17:50 not just even resistance training but balance posture things like that so the more you go deep nutrition
0:17:56 especially we’ve learned a lot about that convincing compelling evidence i would say that you say these
0:18:03 effects we’re talking about just with that seven years more wow of health span free of the major three diseases
0:18:09 wow seven years who wouldn’t take seven years that’s just with what we know today once we can define high
0:18:16 risk which is one of the things we turn to with ai that changes everything because then you focus on that
0:18:21 maybe let’s turn to another aspect of it which is the chronic disease aspect yeah when we’re talking
0:18:27 about chronic disease we’re talking typically about diabetes heart disease cancer how do we start to
0:18:31 make an impact in that i don’t know if you want to pick one if you want to start with cancer i think we
0:18:36 can make a huge impact in cancer because we have just simple polygenic risk scores for all the common
0:18:43 cancers that’s like one layer of data to say you’re at higher risk and we have multi-cancer early detection
0:18:50 tests that can pick up microscopic cancer why people would get a total body mri when you could find
0:18:57 microscopic cancer not a mass on a mri which may or may not be cancer so we have some tools for cancer but
0:19:08 the one thing that i think is unanticipated is the glip one drugs the ozempic zep bound world yes it’s
0:19:15 the most momentous drug class in medical history and we’ve only seen part of the story so far in the
0:19:21 book i write about how it took 20 years to figure out that it wasn’t just about diabetes which is amazing
0:19:30 what if we had ai today and said should we test this for obesity because the developers nova nordisk
0:19:37 and later lily of these drugs they only saw three or four pounds that people with type 2 diabetes would
0:19:45 lose with these drugs and this woman in norway scientist lata nutzen she kept pushing we got to try it in
0:19:50 obesity and they wouldn’t listen to her because well she said diabetics are not losing weight
0:19:57 they finally did it and everyone knows the story 20 30 50 80 pounds of weight loss now when you lose that
0:20:05 much weight for people who are obese you reduce the risk of cancer you reduce the risk of heart disease
0:20:13 and neurodegenerative disease it wouldn’t be surprising to me that now with pills that are remarkably effective
0:20:20 to substitute for injections that can be much less expensively that a large proportion of the
0:20:26 population would be taking one of these drugs or even their successors that is those that are even
0:20:33 more potent and potentially with less side effects so we have a drug class now added to lifestyle factors
0:20:39 we didn’t have before right as you know they are in big trials for preventing alzheimer’s in people
0:20:46 who are not overweight yes okay we’re going to be doing a long covet trial in people who are not
0:20:53 overweight the effects are really quite extraordinary the ability to crack obesity yes we would have been
0:20:58 happy just to do that but all the other things that are coming from it who would have thought that you
0:21:05 could treat prevent addiction yeah that’s remarkable yeah the ability to stop reduce alcohol intake from
0:21:12 heavy intake gambling i mean the list just goes on because we’re learning about the brain circuitry
0:21:20 on how these drugs so some of the secrets of the gut brain axis which is tied into the immune system
0:21:25 and it’s tied into the science of aging this is what’s given us this newfound potential to change
0:21:31 we don’t have to only rely on drugs but there’s this as we discussed this kind of interdependence well and
0:21:37 i think having lifestyle infrastructure with these drugs that combination is particularly interesting
0:21:43 because you can make sure that you can lose weight while keeping muscle and also hopefully patients can
0:21:48 go off the drugs at least for some periods of time and not rebound we don’t have encouraging data at the
0:21:54 moment because at least half of people gain weight back when they stop yeah and that’s not good but i
0:22:02 do think that we’ll come up with a ways to hopefully not rely on such a long-term commitment the results on
0:22:09 muscle mass we’ve been very worried about that and i think when people combine taking the drugs with
0:22:15 strength training and we do know there’s muscle mass loss just with weight alone but that looks encouraging
0:22:21 even though the companies have been acquiring muscle making drugs yes that may not prove to be
0:22:26 particularly necessary well and i think one thing that’s interesting is that another knock on lifestyle
0:22:33 is if you’re extremely obese telling someone to exercise it’s a hard road oh to just get started
0:22:39 absolutely and so this could jump start a better lifestyle that then could get locked in that could be
0:22:45 really i’ve seen it in many patients just what you said couldn’t get them to really increase their
0:22:51 activity but when they were thinner everything changed when you think about if we can make a
0:22:57 huge dent there’s nothing more economically favorable for us at the public population health
0:23:03 level if we can achieve this and so what else would you put into the chronic bucket i think
0:23:08 one of the things that you’ve written about is ai plus all the things you can track i think the ability to
0:23:17 look at the organ clocks which was initially reported here at stanford by tony wiss corey and his colleagues
0:23:25 are now validated and replicated by multiple groups the fact that we can do that and have the brain the
0:23:33 heart the immune system and other vital organs and we can say this one organ of yours is five years
0:23:40 at a pace with your real age then we can integrate that with these other layers of data oh if that’s the
0:23:47 case what about your polygenic risk score is there anything pointing to that disease or organ we can
0:23:55 look at your whole body aging epigenetic horvath clock we can also look at specific proteins like for
0:24:03 example for the brain p tau 217 and what’s amazing about that protein which we can get now and it’s not
0:24:10 that expensive but that in itself gives us over a 20-year warning about mild cognitive impairment
0:24:19 it’s modifiable by exercise and lifestyle we’ve seen people in studies that drop more than 50 percent
0:24:23 even up to 80 percent it’s intriguing that it’s not binary too so you can track the gradient
0:24:28 exactly and that would get particularly scary if it’s increasing so we’re talking about in people
0:24:34 without symptoms but are at high risk having this assist i don’t recommend any of these things that
0:24:41 we’re talking about until you know you have an increased risk but once you do then you say hmm i can do
0:24:47 something about it and change the course of what otherwise would be that person’s natural history but
0:24:56 the molecular clocks this collection of proteins this is something else that’s striking the olink and somalogic
0:25:02 they’re between six and eleven thousand plasma proteins what we’ve learned from them the fact
0:25:08 that there’s three bursts of aging during our life is not just a linear story and the fact that we’re
0:25:14 learning about the underpinnings of diseases but most importantly we have these organ clocks that are
0:25:22 inexpensive to get the uk biobank is only paying fifty dollars per participant wow and they’ve done fifty
0:25:28 thousand and amazing data coming from it but another five hundred thousand is in process so it’s not that
0:25:34 expensive to get such rich data and when you start having genes and proteins and these other layers of
0:25:43 data that’s when you find out what is making us unique and what we are at risk for during our extended time and
0:25:47 and therefore what we should do to change it and improve yeah well let’s take a step back because
0:25:53 i think you’ve been laying out a very appealing picture for what we as individuals could do to
0:25:59 improve our health span get at least seven more years easy maybe more and more and more as the science
0:26:05 improves but you can also think about this from a societal level that the cost of health care is immense
0:26:09 yes just the cost of health care to the u.s government through medicare and medicaid is
0:26:14 approaching two trillion dollars and we live in a time where the united states is in massive debt
0:26:19 there’s a great desire to reduce the deficit or make the deficit negative would be ideal and you look at
0:26:25 health care and people are scared that health care could be cut or something like that and i think no
0:26:30 one wants to remove services but there is this alternative that is very natural from everything you’re
0:26:35 talking about which is that if we can keep people healthier yeah healthier people would be much less
0:26:41 expensive right and we could have a win-win how do we shift the system whether we’re talking about cms
0:26:47 or we’re talking about insurers or providers how do we shift the sick care system to be thinking about
0:26:55 preventative and chronic we have a barrier here because of the malincentives people could change their
0:26:59 insurance companies at any time so the insurance company doesn’t have a long view
0:27:06 whereas other countries like when i did the review of the nhs for the government there they’re well
0:27:13 positioned in the uk and in many countries except for the u.s have a better positioning for this if we
0:27:23 could make prevention now that it is emerging as a reality the priority and say every insurer whether it’s
0:27:29 medicare medicaid private insurers if they don’t pull out all the stops and
0:27:36 if they don’t make this a priority then you know we have to make some pretty drastic policy changes
0:27:43 we’ve not actually accepted yet that we have this newfound capability which completely changes the
0:27:51 economics beyond making a case for healthspan for a population possible and as the people who need
0:28:00 this the most are currently the least likely to get it to access and so this is another issue which if
0:28:08 this only is for the affluent if we don’t take care of everyone we’re not going to achieve that goal so it
0:28:15 can’t just be for people who can have the assets to get this it has to be broadly universally distributed
0:28:22 how can we translate all the existing programs to something that could be let’s say rolled out to
0:28:30 medicare yeah i mean i think that if we negotiated the ai is software it could be cheap whether it’s
0:28:36 some proteins a specific protein polygenic risk score these things can be done twenty dollars fifty
0:28:42 dollars cheaper than most any lab tests that we do right now if we could develop a package negotiated
0:28:49 at a very low rate one way that’s really great vj about this we don’t have to wait 10 years to see the
0:28:55 benefit if we see the clocks all changing in the right direction great idea we have an intermediate surrogate
0:29:03 endpoint so like for example we use ldl cholesterol to know if we have a person’s arteries in check we’re going to have
0:29:12 these proteins like p tau 217 say oh well all these preventative approaches are really kicking in this
0:29:19 should change the likelihood of or if ever developing a neurodegenerative alzheimer’s condition so we have
0:29:26 the metrics again to get a short quick assessment are we making a difference if we did that through cms
0:29:33 that would be phenomenal but maybe we can get one of the big insurers to pilot this to make it possible
0:29:40 if maymad oz is listening maybe he’ll get interested i don’t know yeah i think cms is interested in what
0:29:45 it can do to keep people healthy and reduce cost that’s the canonical win-win i think also as you’ve
0:29:50 written about ai could really have a huge role here too because prevention is expensive if you have to roll
0:29:57 roll this out with gps or nps but to roll out with ai could be very very scalable yeah and i think you made
0:30:04 a point earlier about the ai is that as we do this and we do this at scale it just keeps getting better
0:30:12 so that the ability to predict pinpoint temporally when a person is likely to develop one of these three
0:30:19 three conditions with 20 years runway if we can’t do this for these three diseases we’re not too smart
0:30:26 if ai was before just a few years ago the capabilities wouldn’t be there and neither would
0:30:33 these metrics of aging and all the sciences done to catapult that that’s what’s presented a unique
0:30:40 opportunity and if we don’t do this we’re just stupid well actually let’s double click on that because
0:30:45 there are a lot of enemies of the future you know and maybe a nicer way to put it is that
0:30:50 people could be skeptical yeah and they’re used to operating a certain way they have a certain belief
0:30:56 that this isn’t going to work or for whatever reason what would you tell them like to your fellow
0:31:01 clinical colleagues to try to change their mindset from a sick care mindset to a preventative mindset
0:31:06 yeah i mean it’s to me it’s all about compelling data yeah so for example the alzheimer’s drugs which
0:31:14 don’t really work and they’re very risky but the reason they were bought into by the fda ultimately
0:31:20 was because the amyloid came out on the scans right and there was a little bit of cognitive score
0:31:28 improvement but here we have metrics that are extraordinary to help us as a bridge for compelling
0:31:34 evidence ultimately you want to say we prevented these diseases in people that had definition of their risk
0:31:43 and then active surveillance preventive pull out all the stops right for example speaking about waste we
0:31:52 do mass screening for cancer we treat everyone as the same based on their age and that’s the only criterion
0:31:59 for the screening age we only pick up 14 percent of cancers from that mass screening which costs over
0:32:06 hundreds of hundreds of hundreds of billions of dollars a year now what about 88 of women will
0:32:12 never have breast cancer why do a hundred percent of women have to go through this and especially with
0:32:18 bayes rule you could actually use those priors that you could measure and we don’t do it yeah and this is a
0:32:24 corollary of what we’re talking about why don’t we take the risk profile and say you know what to a
0:32:29 for a woman or for a person having colonoscopy you don’t really ever have to have it or you can have
0:32:36 this once in your lifetime or twice whatever we don’t treat people as human beings with particular
0:32:42 aspects that we can define today and why do you think that is we’re ingrained in stupidity
0:32:49 maybe when these mass screening programs started that was the best we could do yeah but we’ve known about
0:32:55 polygenic risk scores and we learn now about all these other ways to assess risk and then was added
0:33:03 on the ai part of it we have to do better but just having the screening part cleaned up would save a
0:33:09 tremendous amount of money how much is that concerns about liability or other non-medical reasons right
0:33:15 you’re bringing up another good point here because it’s the standard of care so that’s the foundation
0:33:21 for malpractice it shouldn’t be the standard of care there should be a reboot new standard of care
0:33:28 based on intelligent partitioning of risk so each of the cancers there’s a way forward to do this
0:33:35 we have to come up with new ways to screen that is based on risk assessment and we don’t do it but
0:33:41 that could be changed in a flash based on the data that exists today which i review in the book well
0:33:45 that’s all very rational so i just want to double click like what needs to change then what’s the
0:33:50 process is this guidelines have to be done differently and what’s the process and what’s the body that
0:33:56 should be doing this and why aren’t they doing it well i mean we’re seeing how we can have sleeping
0:34:04 changes without data right now yeah so new policies can be made if people want to have more proof points
0:34:10 that can be quickly easily garnered but we have to have the will yeah the problem we have now is the
0:34:17 amount of money that’s being made by doing these screenings is humongous so what is the incentive for
0:34:24 the people that are for example doing the scans and the scopes and all this stuff do they want to change
0:34:31 their practice i don’t know i mean does the american hospital association want to have people in their own home
0:34:36 so they don’t have to go to the hospital i don’t think so we have some things here that need a little
0:34:42 adjustment yeah in any change there’s always new winners and losers and the potential new losers will
0:34:49 fight the change yeah we have a new way forward if we are willing to get it validated and i hope
0:34:55 we’ll seize this opportunity because we may never get another one like this for a long time and what’s
0:35:00 different now is it ai or is it the confluence of all these yeah i think it’s not one without the
0:35:09 other once you have these new ways to assess risk and the ways to i would not just call it intervene
0:35:16 you’re really going after prevention the way you can aggressively put someone in surveillance so with
0:35:23 imaging now for example we can use ai to tell if there’s inflammation in the heart arteries even without
0:35:30 a significant narrowing we didn’t have that before and we can also if we need to do brain imaging it’s
0:35:38 exquisitely sensitive so we have different ways we didn’t have before and the ai part of it is this is
0:35:45 beyond human capability there’s just billions of data points for each person but with the ways that the
0:35:52 models have progressed there’s a new day using ai to promote health and health span so let’s shift
0:35:58 gears talking about the future let’s assume things work out well yeah what is the best case scenario that
0:36:03 you think is plausible what’s the science that’s coming on the horizon let’s say we all decide to make
0:36:09 this shift towards prevention and chronic what do you think we will get for it in our next five to ten years
0:36:15 well i think we’ll start to see that people are eventually getting to much older ages than we are
0:36:22 now without these three major diseases i think that’s a gradual thing it’s not like we’re going to see a
0:36:28 light switch here but that’s what would be the trend we will see countries that will implement it because
0:36:34 they don’t have the obstacles that we have we’ll see much less of that and the shift the bending this
0:36:41 curve to the people that are older and healthier gradually we’re not talking about curing we’re
0:36:46 talking about preventing it’s a lot better than curing but it takes time to see the benefit that’s
0:36:51 a really deep line that prevention is better than curing yeah i think maybe for professionals involved
0:36:57 curing is really cool curing is cool but you don’t want to go there yeah because it’s much harder yeah
0:37:03 prevention is where it’s at well some of that is then even just changing doctor incentives yeah if we can
0:37:10 get them to get them to be rewarded prevention is maybe less connected to their actions it may seem
0:37:14 even though it could have such a great societal benefit yeah but you know and there are health
0:37:20 systems that really do emphasize prevention but they’re rudimentary did you get your pneumococcal
0:37:28 vaccine your drinking and your other social behavioral stuff that’s all types things they haven’t worked
0:37:35 we’re talking about a whole revamping of what we mean by going into prevent mode yeah one question i love
0:37:40 to ask our guests i think i’ve asked this before so it’d be fun to get an update is what do you do for your own
0:37:47 health yeah i’ve gone through some pretty major changes from the work that did to put the book together because
0:37:55 i’m a cardiologist i never really acknowledged that strength training resistant stuff was so important
0:38:02 no less balance and posture so i’ve totally changed that for me i’ve never been this strong in my life
0:38:09 awesome yeah and how does it feel it feels great i mean yeah i just i never paid attention to it i used
0:38:15 to even with patients that came in i’d say well gee you’re really doing a lot of weight lifting here but i was
0:38:20 thinking to myself well they should be spending more time aerobic we need both sleep was a big problem
0:38:27 with me not sleeping and particularly not getting enough deep sleep so i got both a smart watch and
0:38:34 an aura ring to track that i wear both every night and whichever one has the highest number of minutes of
0:38:41 deep sleep i’m going with that but they’re usually concordant after you measure how do you improve yeah i had
0:38:49 to go through a lot of changes okay so i needed to get like a ritual when i go to bed wake up which i was
0:38:58 erratic about and i also learned about when to exercise what to eat not to eat all these interactions when
0:39:06 should you exercise well early if i can not too late in the afternoon but not in the evening and for me the
0:39:13 morning had a negative interaction with sleep really exercising the morning yeah yeah i mean i dragged all
0:39:19 day because i do an hour hour and a half if i can but the morning just wasn’t working for me but late
0:39:25 afternoon no later than that but also learning about whether it’s alcohol other beverages how they affected me
0:39:32 caffeine probably yeah so i basically i’ve gone from a deep sleep i’ve doubled it pushing i’m working on
0:39:37 getting i don’t know if i’ll get to triple it but you know it’s been a steady trend and it’s been really
0:39:45 great and giving me more energy more readiness and all that now the other one besides those two i’ve really
0:39:52 gone after the nutrition so i didn’t realize how much ultra processed food i took in yeah it’s so easy
0:39:58 reading the labels now i don’t even want to have a label to read just stay away from it if it has a
0:40:03 label and it has anything more than two ingredients anything i don’t know that would be that’s a really
0:40:08 interesting point broccoli doesn’t have a label yeah and the steak doesn’t have no no i just i
0:40:15 completely bought in now because these three age-related diseases inflammation all of them have been
0:40:21 associated with ultra processed foods a dose response even and i have really cut that out i mean i
0:40:27 couldn’t relieve how much stuff i was eating that had this junk in there i’m also really attentive to
0:40:33 things like plastics i don’t like to see anything being stored in plastic i don’t even like to use
0:40:40 microwave but putting something in plastic in a microwave that is a triple wham yeah but we are taking
0:40:47 in these plastics in the artery with people have a four-fold or five-fold risk of heart attacks and
0:40:54 strokes once you see that study it just is indelible so that’s another big change i’m much more focused on
0:41:01 these environmental burdens but the other thing is much more inclined now to take hikes in nature
0:41:07 to go out you see the benefit of that yeah i mean i think that when i’m out in nature and of course the
0:41:13 data i presented in the book i always appreciate it but now i can see its effects even more impact with
0:41:20 respect to for example the best sleep surprisingly so what i’ve learned i’ve tried to share i don’t
0:41:26 really speak too much or write too much about myself in the book but all these things i’m doing i mean
0:41:30 i believe in them if i didn’t believe them i wouldn’t have written about them and it was after calling
0:41:37 through there’s about 1800 references in there so people can look at themselves and see what they think but
0:41:43 it’s data that i’ve really been impressed it’s a body of evidence that ought to push us into this
0:41:48 prevent mode and i hope that eventually it will yeah but that’s maybe a great place to end i think
0:41:53 we could follow your example we could all be super agents thank you vj it’s been a real pleasure
0:42:01 thanks for listening to the a16z podcast if you enjoyed the episode let us know by leaving a review at
0:42:15 rate this podcast dot com slash a16z we’ve got more great conversations coming your way see you next time
0:00:12 isn’t reversing aging it’s just preventing the age-related morbidities
0:00:16 of the big three if we can keep people healthier healthier people would be much
0:00:22 less expensive seven years more of healthspan free of the major three
0:00:27 diseases seven years who wouldn’t take seven years there’s just billions of
0:00:33 data points for each person there should be a reboot new standard of care based on
0:00:41 intelligent partitioning of risk we have to do better the human obsession with
0:00:46 living longer is as old as time but in the last 20 years we have learned so much
0:00:51 more about human health and biology so what do we know today about what makes
0:00:56 humans live longer and do we have real evidence that longevity is an attackable
0:01:01 target today you’ll get to hear a 16th general partner vj ponday in conversation
0:01:06 with eric topol who recently released his new book super agers an evidence-based
0:01:11 approach to longevity eric is among other things the founder and director of the
0:01:16 scripps research translational institute he’s also published over 1200 peer-reviewed
0:01:21 articles with more than 300,000 citations making him one of the 10 most cited
0:01:26 investigators in medicine that resume puts eric in a perfect position to write this book
0:01:31 teasing the signal out from all the noise around health in 2025 one of those inputs
0:01:37 was the welderly group that eric studied which was a study of 1400 people 80 plus who
0:01:42 had never developed a chronic illness for comparison according to eric’s book among
0:01:49 those 65 plus 80 percent have two or more chronic diseases and 23 percent have three or more well
0:01:55 about seven percent have five or more and again that was the 65 plus group versus the welderly
0:02:02 group of 80 plus so what do we know about these quote super agers people who not only have a
0:02:07 longer lifespan but a longer health span is it genetics or human agency and do technologies
0:02:13 like ai glp ones gene therapies or the ability to understand organ clocks meaningfully change that
0:02:20 equation for the masses if so what difficult decisions do we have to make to rewrite the system today let’s
0:02:28 find out as a reminder the content here is for informational purposes only should not be taken
0:02:33 as legal business tax or investment advice or be used to evaluate any investment or security and is
0:02:39 not directed at any investors or potential investors in any a16z fund please note that a16z and its affiliates
0:02:44 may also maintain investments in the companies discussed in this podcast for more details including a link
0:02:49 to our investments please see a16z.com forward slash disclosures
0:03:00 my joy to welcome dr eric topol to the podcast eric thanks so much for joining us i’m glad to be here
0:03:08 so you’ve written this really exciting book super agers and evidence-based path to longevity and i think
0:03:13 it’s a very timely topic and i was curious for you to maybe set the stage for why you want to write it
0:03:18 and how you see it in the context of other books that have been coming out recently as well yeah there
0:03:25 were a few things that came together we had done a big study we called the welderly where we basically
0:03:32 found very little in the genomes of people who had gone to the age of 87 on average with never having
0:03:39 had an age-related disease so that was of course one thing that was part of it the second was i got inspired
0:03:47 by a patient i saw recently who was 98 and had never been sick and so never been sick yeah her name
0:03:55 is lee rissall and her relatives had died in their 50s and 60s that’s her parents her uncles and aunts
0:04:02 she was the outlier and say why and then there were the books that came out i had patients coming to me
0:04:07 you know they wanted me to write a prescription for apple my sin or order a total body mri said wait we
0:04:13 got to get the story straight so these three things together were the impetus that why don’t i really
0:04:20 get deep into this everything we know today and then see if i could lay out some blueprints for where we can
0:04:27 go it’s coming into a world where american health care is in crisis i was curious to get your take on
0:04:33 where we are now in health care in the us and where do you think we get to yeah so there is this
0:04:39 bifurcation as i see it you could call it like the grand slam where you get reversing of aging so you
0:04:47 keep people healthier body-wide and that’s where we see all this remarkable investments in companies like
0:04:54 altos and reprogramming senolytics and a long list but they’re really focused on a monumental task which
0:05:01 hasn’t been shown in people right but rather in rodents and some of the results are striking and
0:05:07 i hope at least one if not all these are successful the other side of this is we’ve made these big strides
0:05:14 in the science of aging with all these layers of data that are using the metrics of aging and why don’t we
0:05:21 use that to prevent the age-related diseases cancer cardiovascular neurodegenerative we’ve never done
0:05:29 that in medicine to any appreciable extent and this is the opportunity because we have a path to
0:05:35 preventing disease it isn’t reversing aging it’s just preventing the age-related morbidities of the
0:05:40 big three i think that’s something that a lot of people may not realize is that the big three that you
0:05:48 mentioned cancer heart disease and alzheimer’s and dementia that they’re greatly exacerbated by age and
0:05:52 and it’s interesting because if you ever wanted to have something that could be a cure for multiple
0:05:57 diseases which would be the one the holy grails of medicine it would be understanding the biology of
0:06:03 aging where are we now in terms of things that we can use today the first and perhaps the most extraordinary
0:06:11 thing is it takes 20 years to get these diseases with rare exception you know for heart disease
0:06:18 almost all cancers and neurodegenerative they are incubating for a very long time they all have a
0:06:28 common thread of a defective immune system and inflammation underpinning they are preventable
0:06:37 variably so cardiovascular 80 90 from lifestyle and related factors modifiable factors like your ldl
0:06:43 cholesterol that kind of thing and cancer and neurodegenerative just from what we know today
0:06:50 with lifestyle factors we’re about half that can be prevented so we have some knowledge about averting these
0:06:57 diseases but we have a lot more with all these clocks and new layers of data that are really changing the
0:07:04 face of all outgrowths of understanding the biology of aging so maybe let’s double click on that so you
0:07:09 in your book outline the five dimensions of health i was wondering maybe you could walk us through them
0:07:18 yeah yeah sure so the first most important one is ai because you need that to pull all this other
0:07:24 data we’re going to talk about together this moment that is so exciting is because we have multimodal ai
0:07:29 not only large language but large reasoning models now well especially i think when you’re talking about
0:07:34 ai it’s all the things people have seen with generative ai and so on but also just the ability to
0:07:39 understand all this data yes that you’re measuring from people yeah because the other four are such big
0:07:47 domains and dimensions so the omics it includes not just gene sequence or arrays but it has all the
0:07:54 proteins all the proteomic panels that we can get which we never could get before inexpensively it
0:08:02 includes the gut microbiome metabolome and certainly epigenome or epigenetics so the omics are rich
0:08:10 we are now seeing moving in towards things like the virtual cell then there is of course cells that
0:08:16 have become a live drug where we can reset the immune system and cure autoimmune diseases like we’ve never
0:08:23 done before could you give examples of that yeah so in the last couple years we’ve seen unprecedented
0:08:31 cures i mean never had anything lupus progressive systemic sclerosis even cases of multiple sclerosis
0:08:39 dermatomyositis so basically it’s a depletion of all the b cells and when they come back
0:08:44 they have forgotten what they were attacking it’s amazing yes it’s really amazing that leads to the
0:08:49 autoimmune reaction but the bigger lesson is we have learned how to control our immune system
0:08:56 like a rheostat and we’re going to keep getting better and better as we measure our immunom but when you can do
0:09:05 that when you can quash an autoimmune disease or when you’re trying to cure a cancer by just whatever it
0:09:12 takes to keep bringing up that immune system specific to the tumor so the immune system is fundamental and
0:09:21 that also now is involving cells and vaccines so vaccines now are capable of cures of pancreatic
0:09:28 cancer kidney cancer with these personalized vaccines using the proteins of the person’s tumor yes and
0:09:34 these are in clinical trials right now yeah i mean they’re stuff like we’ve never seen and that’s just a
0:09:41 front runner of what vaccines that’s to treat cancer we’re going to be using vaccines to prevent cancer
0:09:48 again as we get older some of us especially our immune system is getting senescent and weak and a
0:09:54 vaccine before there’s any cancer before there’s anything else could prop it up we also have drugs to
0:10:01 modulate our immune system well beyond checkpoint inhibitors and so whether it’s antibody drug
0:10:08 conjugates tumor infiltrating lymphocytes and all these different ways it’s hard to imagine that in the
0:10:13 future we’re going to lose people with cancer because of being able to bring their immune system to the
0:10:20 highest level when we need it but more importantly preventing the cancer we can do that now that’s what’s exciting
0:10:26 well and so if we put all this together what does this mean for the individual like how would their
0:10:33 life change what should people be doing yeah so i call it lifestyle plus it’s a lot bigger than diet
0:10:40 sleep and exercise it’s involving you know all the environmental burdens air pollution the plastics
0:10:46 microplastics nanoplastics and forever chemicals and then there’s other things like time in nature
0:10:53 so if each of us pulled out all the stops for the lifestyle factors which is a long list that will
0:11:01 help but it’s not going to be only lifestyle factors that are the ways to prevent the big three age-related
0:11:07 diseases you know you described a large range of things from the sort of most almost sci-fi like
0:11:12 drugs that are in trials for preventing cancer to lifestyle when people think about lifestyle it’s
0:11:17 maybe a little vague in their mind for what to do how do you make that into a science or how do you
0:11:23 help people take that to the next step to bring evidence into that i go into perhaps great pains high
0:11:32 density to cite all the studies that link like for example when you have really good sleep health and deep
0:11:38 sleep what does that do to slow your brain aging or you know if you drink sugar sweetened beverages
0:11:45 what does that do to specific not just risk of type 2 diabetes but you know all-cause mortality so
0:11:55 there are very compelling sets of data about lifestyles and these key outcomes and they’re linked to healthy
0:12:00 aging i was amazed how much data is out there that can help us it’s not just like in the year when we had
0:12:07 polygenic risk scores and we just say oh your risk for alzheimer’s but we don’t know if when you’re age 56 or 96
0:12:14 so what good is that yes now we’re saying we know it’s within a couple of years between 77 and 79
0:12:20 that you’re going to have mild cognitive impairment if we don’t do these things which includes the
0:12:27 lifestyle factors and it’s much harder to get people to do all their stuff they have no specificity that’s
0:12:35 that it’s about them yeah that they can change the arc of a condition especially when it isn’t our genes the healthy
0:12:42 story about a genetic underpinning it’s just not there we studied that it’s minimal i mean maybe it’s ten percent of what
0:12:51 accounts for healthy aging most of it is in the lifestyle factors and related matters such as the immune system
0:12:57 not functioning properly too much too little well it’s generally believed that just telling someone to
0:13:03 eat better and exercise doesn’t work but what i’m hearing you say is that you have a way to do that by
0:13:09 making it very personalized yes i mean there was a finnish study that was on just polygenic risk
0:13:16 score which is rudimentary and they gave that to a large cohort and they studied whether that affected
0:13:23 their lifestyle and the results were remarkable the people who got the data stopped smoking changed
0:13:28 their diet changed their physical activity really amped it up so we know when people get data that’s
0:13:36 specific to them a large proportion much more likely to make changes now i’m not claiming that lifestyle is
0:13:43 going to be the only part of the prevention story but once you define the high risk and it’s
0:13:48 particularized to a person that’s a big part of how we’re going to succeed i could also imagine ai coming
0:13:53 into this because one of the things ai is very good at is to take a set of data and maybe you can mask
0:13:59 out the last bit so you can maybe have someone’s health records over 30 years and train on that except for
0:14:05 the last five years and see if you can predict the last five from the first 25 and once it gets really
0:14:10 good at that you can take my records and say hey look vj if you don’t do anything this is where you’re
0:14:17 going to be and we have 99 confidence on this that would be pretty chilling yeah well you’re exactly
0:14:23 right because the pinpointing here about the timing yeah is so extraordinary for example with alzheimer’s
0:14:31 since we were talking about that you get a p tau 217 it’s modifiable by lifestyle you check it again in
0:14:37 six months or a year now you have two data points and you could say with all the other data that’s
0:14:44 available when you’re going to see 18 years from now 12 years four years mild cognitive impairment
0:14:51 unless these steps are taken this was fully dependent on ai on models that can just take all
0:14:59 this data if we didn’t have the science of aging and the ai we’d be nowhere we wouldn’t be talking about
0:15:03 this today i wouldn’t have written a book yeah well it’s important for people not familiar with the term
0:15:08 of health span that’s basically not just lifespan but how long you can be healthy yeah i don’t think we
0:15:14 really want to get to some age and be demented or compromised what we’re talking about is if you
0:15:20 don’t have heart disease cancer or neurodegenerative you’re pretty darn intact you may have some achy
0:15:27 joints and other matters but those are the things that really interrupt our health span now we’re
0:15:31 talking about health care meaning something different to be preventative and we’ll talk
0:15:38 about chronic in a second how do we help make that mind shift this is perhaps the biggest point so far
0:15:44 that we’ve been discussing because in medicine and i’ve been in it for almost 40 years we don’t do
0:15:50 primary prevention the person has a heart attack and then we get all over it but for the most part
0:15:57 we don’t prevent cancer we don’t prevent alzheimer’s and neurodegenerative diseases it’s been a desire i
0:16:04 would say a fantasy for millennia yes but we are at a very different point right now we have a path to
0:16:12 prevention primary prevention not after somebody has one of these diseases and that is what is extraordinary
0:16:20 and it was all these recent advances that led to this capability and we’ve got to jump on it because
0:16:25 it’s exciting that we could actually do this well also the thing about prevention is that i’ve talked
0:16:32 to doctors who very boldly assert that prevention doesn’t work yeah and i look at them a bit confused
0:16:37 because i say well there’s been numerous examples and they’re like well name one i was like how about
0:16:42 smoking that’s the prototype we have this huge incidence of lung cancer which has just disappeared
0:16:48 now because we don’t smoke in restaurants or airplanes and so on but one of the things that i think about
0:16:53 about that movement is that while doctors played a significant role in that that was also very much
0:16:59 a cultural movement yes and so we talked about lifestyle changing people’s behaviors i think some of
0:17:04 this or much of this has to be as much cultural as medical there’s a definite cultural component and you
0:17:10 know tobacco is one of the most impressive but there’s so many others yes i think what we’ve learned
0:17:17 like for example with sleep i didn’t pay enough attention to that but with sleep when you promote your own
0:17:27 deep sleep which we tend to lose a lot as we age then you see much less dementia alzheimer’s even less
0:17:36 cardiovascular and cancer related illnesses cases and mortality sleep regularity we need to be more ritualistic
0:17:42 about it and there are many things just on sleep itself no less about physical activity about for example
0:17:50 not just even resistance training but balance posture things like that so the more you go deep nutrition
0:17:56 especially we’ve learned a lot about that convincing compelling evidence i would say that you say these
0:18:03 effects we’re talking about just with that seven years more wow of health span free of the major three diseases
0:18:09 wow seven years who wouldn’t take seven years that’s just with what we know today once we can define high
0:18:16 risk which is one of the things we turn to with ai that changes everything because then you focus on that
0:18:21 maybe let’s turn to another aspect of it which is the chronic disease aspect yeah when we’re talking
0:18:27 about chronic disease we’re talking typically about diabetes heart disease cancer how do we start to
0:18:31 make an impact in that i don’t know if you want to pick one if you want to start with cancer i think we
0:18:36 can make a huge impact in cancer because we have just simple polygenic risk scores for all the common
0:18:43 cancers that’s like one layer of data to say you’re at higher risk and we have multi-cancer early detection
0:18:50 tests that can pick up microscopic cancer why people would get a total body mri when you could find
0:18:57 microscopic cancer not a mass on a mri which may or may not be cancer so we have some tools for cancer but
0:19:08 the one thing that i think is unanticipated is the glip one drugs the ozempic zep bound world yes it’s
0:19:15 the most momentous drug class in medical history and we’ve only seen part of the story so far in the
0:19:21 book i write about how it took 20 years to figure out that it wasn’t just about diabetes which is amazing
0:19:30 what if we had ai today and said should we test this for obesity because the developers nova nordisk
0:19:37 and later lily of these drugs they only saw three or four pounds that people with type 2 diabetes would
0:19:45 lose with these drugs and this woman in norway scientist lata nutzen she kept pushing we got to try it in
0:19:50 obesity and they wouldn’t listen to her because well she said diabetics are not losing weight
0:19:57 they finally did it and everyone knows the story 20 30 50 80 pounds of weight loss now when you lose that
0:20:05 much weight for people who are obese you reduce the risk of cancer you reduce the risk of heart disease
0:20:13 and neurodegenerative disease it wouldn’t be surprising to me that now with pills that are remarkably effective
0:20:20 to substitute for injections that can be much less expensively that a large proportion of the
0:20:26 population would be taking one of these drugs or even their successors that is those that are even
0:20:33 more potent and potentially with less side effects so we have a drug class now added to lifestyle factors
0:20:39 we didn’t have before right as you know they are in big trials for preventing alzheimer’s in people
0:20:46 who are not overweight yes okay we’re going to be doing a long covet trial in people who are not
0:20:53 overweight the effects are really quite extraordinary the ability to crack obesity yes we would have been
0:20:58 happy just to do that but all the other things that are coming from it who would have thought that you
0:21:05 could treat prevent addiction yeah that’s remarkable yeah the ability to stop reduce alcohol intake from
0:21:12 heavy intake gambling i mean the list just goes on because we’re learning about the brain circuitry
0:21:20 on how these drugs so some of the secrets of the gut brain axis which is tied into the immune system
0:21:25 and it’s tied into the science of aging this is what’s given us this newfound potential to change
0:21:31 we don’t have to only rely on drugs but there’s this as we discussed this kind of interdependence well and
0:21:37 i think having lifestyle infrastructure with these drugs that combination is particularly interesting
0:21:43 because you can make sure that you can lose weight while keeping muscle and also hopefully patients can
0:21:48 go off the drugs at least for some periods of time and not rebound we don’t have encouraging data at the
0:21:54 moment because at least half of people gain weight back when they stop yeah and that’s not good but i
0:22:02 do think that we’ll come up with a ways to hopefully not rely on such a long-term commitment the results on
0:22:09 muscle mass we’ve been very worried about that and i think when people combine taking the drugs with
0:22:15 strength training and we do know there’s muscle mass loss just with weight alone but that looks encouraging
0:22:21 even though the companies have been acquiring muscle making drugs yes that may not prove to be
0:22:26 particularly necessary well and i think one thing that’s interesting is that another knock on lifestyle
0:22:33 is if you’re extremely obese telling someone to exercise it’s a hard road oh to just get started
0:22:39 absolutely and so this could jump start a better lifestyle that then could get locked in that could be
0:22:45 really i’ve seen it in many patients just what you said couldn’t get them to really increase their
0:22:51 activity but when they were thinner everything changed when you think about if we can make a
0:22:57 huge dent there’s nothing more economically favorable for us at the public population health
0:23:03 level if we can achieve this and so what else would you put into the chronic bucket i think
0:23:08 one of the things that you’ve written about is ai plus all the things you can track i think the ability to
0:23:17 look at the organ clocks which was initially reported here at stanford by tony wiss corey and his colleagues
0:23:25 are now validated and replicated by multiple groups the fact that we can do that and have the brain the
0:23:33 heart the immune system and other vital organs and we can say this one organ of yours is five years
0:23:40 at a pace with your real age then we can integrate that with these other layers of data oh if that’s the
0:23:47 case what about your polygenic risk score is there anything pointing to that disease or organ we can
0:23:55 look at your whole body aging epigenetic horvath clock we can also look at specific proteins like for
0:24:03 example for the brain p tau 217 and what’s amazing about that protein which we can get now and it’s not
0:24:10 that expensive but that in itself gives us over a 20-year warning about mild cognitive impairment
0:24:19 it’s modifiable by exercise and lifestyle we’ve seen people in studies that drop more than 50 percent
0:24:23 even up to 80 percent it’s intriguing that it’s not binary too so you can track the gradient
0:24:28 exactly and that would get particularly scary if it’s increasing so we’re talking about in people
0:24:34 without symptoms but are at high risk having this assist i don’t recommend any of these things that
0:24:41 we’re talking about until you know you have an increased risk but once you do then you say hmm i can do
0:24:47 something about it and change the course of what otherwise would be that person’s natural history but
0:24:56 the molecular clocks this collection of proteins this is something else that’s striking the olink and somalogic
0:25:02 they’re between six and eleven thousand plasma proteins what we’ve learned from them the fact
0:25:08 that there’s three bursts of aging during our life is not just a linear story and the fact that we’re
0:25:14 learning about the underpinnings of diseases but most importantly we have these organ clocks that are
0:25:22 inexpensive to get the uk biobank is only paying fifty dollars per participant wow and they’ve done fifty
0:25:28 thousand and amazing data coming from it but another five hundred thousand is in process so it’s not that
0:25:34 expensive to get such rich data and when you start having genes and proteins and these other layers of
0:25:43 data that’s when you find out what is making us unique and what we are at risk for during our extended time and
0:25:47 and therefore what we should do to change it and improve yeah well let’s take a step back because
0:25:53 i think you’ve been laying out a very appealing picture for what we as individuals could do to
0:25:59 improve our health span get at least seven more years easy maybe more and more and more as the science
0:26:05 improves but you can also think about this from a societal level that the cost of health care is immense
0:26:09 yes just the cost of health care to the u.s government through medicare and medicaid is
0:26:14 approaching two trillion dollars and we live in a time where the united states is in massive debt
0:26:19 there’s a great desire to reduce the deficit or make the deficit negative would be ideal and you look at
0:26:25 health care and people are scared that health care could be cut or something like that and i think no
0:26:30 one wants to remove services but there is this alternative that is very natural from everything you’re
0:26:35 talking about which is that if we can keep people healthier yeah healthier people would be much less
0:26:41 expensive right and we could have a win-win how do we shift the system whether we’re talking about cms
0:26:47 or we’re talking about insurers or providers how do we shift the sick care system to be thinking about
0:26:55 preventative and chronic we have a barrier here because of the malincentives people could change their
0:26:59 insurance companies at any time so the insurance company doesn’t have a long view
0:27:06 whereas other countries like when i did the review of the nhs for the government there they’re well
0:27:13 positioned in the uk and in many countries except for the u.s have a better positioning for this if we
0:27:23 could make prevention now that it is emerging as a reality the priority and say every insurer whether it’s
0:27:29 medicare medicaid private insurers if they don’t pull out all the stops and
0:27:36 if they don’t make this a priority then you know we have to make some pretty drastic policy changes
0:27:43 we’ve not actually accepted yet that we have this newfound capability which completely changes the
0:27:51 economics beyond making a case for healthspan for a population possible and as the people who need
0:28:00 this the most are currently the least likely to get it to access and so this is another issue which if
0:28:08 this only is for the affluent if we don’t take care of everyone we’re not going to achieve that goal so it
0:28:15 can’t just be for people who can have the assets to get this it has to be broadly universally distributed
0:28:22 how can we translate all the existing programs to something that could be let’s say rolled out to
0:28:30 medicare yeah i mean i think that if we negotiated the ai is software it could be cheap whether it’s
0:28:36 some proteins a specific protein polygenic risk score these things can be done twenty dollars fifty
0:28:42 dollars cheaper than most any lab tests that we do right now if we could develop a package negotiated
0:28:49 at a very low rate one way that’s really great vj about this we don’t have to wait 10 years to see the
0:28:55 benefit if we see the clocks all changing in the right direction great idea we have an intermediate surrogate
0:29:03 endpoint so like for example we use ldl cholesterol to know if we have a person’s arteries in check we’re going to have
0:29:12 these proteins like p tau 217 say oh well all these preventative approaches are really kicking in this
0:29:19 should change the likelihood of or if ever developing a neurodegenerative alzheimer’s condition so we have
0:29:26 the metrics again to get a short quick assessment are we making a difference if we did that through cms
0:29:33 that would be phenomenal but maybe we can get one of the big insurers to pilot this to make it possible
0:29:40 if maymad oz is listening maybe he’ll get interested i don’t know yeah i think cms is interested in what
0:29:45 it can do to keep people healthy and reduce cost that’s the canonical win-win i think also as you’ve
0:29:50 written about ai could really have a huge role here too because prevention is expensive if you have to roll
0:29:57 roll this out with gps or nps but to roll out with ai could be very very scalable yeah and i think you made
0:30:04 a point earlier about the ai is that as we do this and we do this at scale it just keeps getting better
0:30:12 so that the ability to predict pinpoint temporally when a person is likely to develop one of these three
0:30:19 three conditions with 20 years runway if we can’t do this for these three diseases we’re not too smart
0:30:26 if ai was before just a few years ago the capabilities wouldn’t be there and neither would
0:30:33 these metrics of aging and all the sciences done to catapult that that’s what’s presented a unique
0:30:40 opportunity and if we don’t do this we’re just stupid well actually let’s double click on that because
0:30:45 there are a lot of enemies of the future you know and maybe a nicer way to put it is that
0:30:50 people could be skeptical yeah and they’re used to operating a certain way they have a certain belief
0:30:56 that this isn’t going to work or for whatever reason what would you tell them like to your fellow
0:31:01 clinical colleagues to try to change their mindset from a sick care mindset to a preventative mindset
0:31:06 yeah i mean it’s to me it’s all about compelling data yeah so for example the alzheimer’s drugs which
0:31:14 don’t really work and they’re very risky but the reason they were bought into by the fda ultimately
0:31:20 was because the amyloid came out on the scans right and there was a little bit of cognitive score
0:31:28 improvement but here we have metrics that are extraordinary to help us as a bridge for compelling
0:31:34 evidence ultimately you want to say we prevented these diseases in people that had definition of their risk
0:31:43 and then active surveillance preventive pull out all the stops right for example speaking about waste we
0:31:52 do mass screening for cancer we treat everyone as the same based on their age and that’s the only criterion
0:31:59 for the screening age we only pick up 14 percent of cancers from that mass screening which costs over
0:32:06 hundreds of hundreds of hundreds of billions of dollars a year now what about 88 of women will
0:32:12 never have breast cancer why do a hundred percent of women have to go through this and especially with
0:32:18 bayes rule you could actually use those priors that you could measure and we don’t do it yeah and this is a
0:32:24 corollary of what we’re talking about why don’t we take the risk profile and say you know what to a
0:32:29 for a woman or for a person having colonoscopy you don’t really ever have to have it or you can have
0:32:36 this once in your lifetime or twice whatever we don’t treat people as human beings with particular
0:32:42 aspects that we can define today and why do you think that is we’re ingrained in stupidity
0:32:49 maybe when these mass screening programs started that was the best we could do yeah but we’ve known about
0:32:55 polygenic risk scores and we learn now about all these other ways to assess risk and then was added
0:33:03 on the ai part of it we have to do better but just having the screening part cleaned up would save a
0:33:09 tremendous amount of money how much is that concerns about liability or other non-medical reasons right
0:33:15 you’re bringing up another good point here because it’s the standard of care so that’s the foundation
0:33:21 for malpractice it shouldn’t be the standard of care there should be a reboot new standard of care
0:33:28 based on intelligent partitioning of risk so each of the cancers there’s a way forward to do this
0:33:35 we have to come up with new ways to screen that is based on risk assessment and we don’t do it but
0:33:41 that could be changed in a flash based on the data that exists today which i review in the book well
0:33:45 that’s all very rational so i just want to double click like what needs to change then what’s the
0:33:50 process is this guidelines have to be done differently and what’s the process and what’s the body that
0:33:56 should be doing this and why aren’t they doing it well i mean we’re seeing how we can have sleeping
0:34:04 changes without data right now yeah so new policies can be made if people want to have more proof points
0:34:10 that can be quickly easily garnered but we have to have the will yeah the problem we have now is the
0:34:17 amount of money that’s being made by doing these screenings is humongous so what is the incentive for
0:34:24 the people that are for example doing the scans and the scopes and all this stuff do they want to change
0:34:31 their practice i don’t know i mean does the american hospital association want to have people in their own home
0:34:36 so they don’t have to go to the hospital i don’t think so we have some things here that need a little
0:34:42 adjustment yeah in any change there’s always new winners and losers and the potential new losers will
0:34:49 fight the change yeah we have a new way forward if we are willing to get it validated and i hope
0:34:55 we’ll seize this opportunity because we may never get another one like this for a long time and what’s
0:35:00 different now is it ai or is it the confluence of all these yeah i think it’s not one without the
0:35:09 other once you have these new ways to assess risk and the ways to i would not just call it intervene
0:35:16 you’re really going after prevention the way you can aggressively put someone in surveillance so with
0:35:23 imaging now for example we can use ai to tell if there’s inflammation in the heart arteries even without
0:35:30 a significant narrowing we didn’t have that before and we can also if we need to do brain imaging it’s
0:35:38 exquisitely sensitive so we have different ways we didn’t have before and the ai part of it is this is
0:35:45 beyond human capability there’s just billions of data points for each person but with the ways that the
0:35:52 models have progressed there’s a new day using ai to promote health and health span so let’s shift
0:35:58 gears talking about the future let’s assume things work out well yeah what is the best case scenario that
0:36:03 you think is plausible what’s the science that’s coming on the horizon let’s say we all decide to make
0:36:09 this shift towards prevention and chronic what do you think we will get for it in our next five to ten years
0:36:15 well i think we’ll start to see that people are eventually getting to much older ages than we are
0:36:22 now without these three major diseases i think that’s a gradual thing it’s not like we’re going to see a
0:36:28 light switch here but that’s what would be the trend we will see countries that will implement it because
0:36:34 they don’t have the obstacles that we have we’ll see much less of that and the shift the bending this
0:36:41 curve to the people that are older and healthier gradually we’re not talking about curing we’re
0:36:46 talking about preventing it’s a lot better than curing but it takes time to see the benefit that’s
0:36:51 a really deep line that prevention is better than curing yeah i think maybe for professionals involved
0:36:57 curing is really cool curing is cool but you don’t want to go there yeah because it’s much harder yeah
0:37:03 prevention is where it’s at well some of that is then even just changing doctor incentives yeah if we can
0:37:10 get them to get them to be rewarded prevention is maybe less connected to their actions it may seem
0:37:14 even though it could have such a great societal benefit yeah but you know and there are health
0:37:20 systems that really do emphasize prevention but they’re rudimentary did you get your pneumococcal
0:37:28 vaccine your drinking and your other social behavioral stuff that’s all types things they haven’t worked
0:37:35 we’re talking about a whole revamping of what we mean by going into prevent mode yeah one question i love
0:37:40 to ask our guests i think i’ve asked this before so it’d be fun to get an update is what do you do for your own
0:37:47 health yeah i’ve gone through some pretty major changes from the work that did to put the book together because
0:37:55 i’m a cardiologist i never really acknowledged that strength training resistant stuff was so important
0:38:02 no less balance and posture so i’ve totally changed that for me i’ve never been this strong in my life
0:38:09 awesome yeah and how does it feel it feels great i mean yeah i just i never paid attention to it i used
0:38:15 to even with patients that came in i’d say well gee you’re really doing a lot of weight lifting here but i was
0:38:20 thinking to myself well they should be spending more time aerobic we need both sleep was a big problem
0:38:27 with me not sleeping and particularly not getting enough deep sleep so i got both a smart watch and
0:38:34 an aura ring to track that i wear both every night and whichever one has the highest number of minutes of
0:38:41 deep sleep i’m going with that but they’re usually concordant after you measure how do you improve yeah i had
0:38:49 to go through a lot of changes okay so i needed to get like a ritual when i go to bed wake up which i was
0:38:58 erratic about and i also learned about when to exercise what to eat not to eat all these interactions when
0:39:06 should you exercise well early if i can not too late in the afternoon but not in the evening and for me the
0:39:13 morning had a negative interaction with sleep really exercising the morning yeah yeah i mean i dragged all
0:39:19 day because i do an hour hour and a half if i can but the morning just wasn’t working for me but late
0:39:25 afternoon no later than that but also learning about whether it’s alcohol other beverages how they affected me
0:39:32 caffeine probably yeah so i basically i’ve gone from a deep sleep i’ve doubled it pushing i’m working on
0:39:37 getting i don’t know if i’ll get to triple it but you know it’s been a steady trend and it’s been really
0:39:45 great and giving me more energy more readiness and all that now the other one besides those two i’ve really
0:39:52 gone after the nutrition so i didn’t realize how much ultra processed food i took in yeah it’s so easy
0:39:58 reading the labels now i don’t even want to have a label to read just stay away from it if it has a
0:40:03 label and it has anything more than two ingredients anything i don’t know that would be that’s a really
0:40:08 interesting point broccoli doesn’t have a label yeah and the steak doesn’t have no no i just i
0:40:15 completely bought in now because these three age-related diseases inflammation all of them have been
0:40:21 associated with ultra processed foods a dose response even and i have really cut that out i mean i
0:40:27 couldn’t relieve how much stuff i was eating that had this junk in there i’m also really attentive to
0:40:33 things like plastics i don’t like to see anything being stored in plastic i don’t even like to use
0:40:40 microwave but putting something in plastic in a microwave that is a triple wham yeah but we are taking
0:40:47 in these plastics in the artery with people have a four-fold or five-fold risk of heart attacks and
0:40:54 strokes once you see that study it just is indelible so that’s another big change i’m much more focused on
0:41:01 these environmental burdens but the other thing is much more inclined now to take hikes in nature
0:41:07 to go out you see the benefit of that yeah i mean i think that when i’m out in nature and of course the
0:41:13 data i presented in the book i always appreciate it but now i can see its effects even more impact with
0:41:20 respect to for example the best sleep surprisingly so what i’ve learned i’ve tried to share i don’t
0:41:26 really speak too much or write too much about myself in the book but all these things i’m doing i mean
0:41:30 i believe in them if i didn’t believe them i wouldn’t have written about them and it was after calling
0:41:37 through there’s about 1800 references in there so people can look at themselves and see what they think but
0:41:43 it’s data that i’ve really been impressed it’s a body of evidence that ought to push us into this
0:41:48 prevent mode and i hope that eventually it will yeah but that’s maybe a great place to end i think
0:41:53 we could follow your example we could all be super agents thank you vj it’s been a real pleasure
0:42:01 thanks for listening to the a16z podcast if you enjoyed the episode let us know by leaving a review at
0:42:15 rate this podcast dot com slash a16z we’ve got more great conversations coming your way see you next time
American healthcare is in crisis—but what if we could change the system by preventing disease before it starts?
In this episode of the a16z Podcast, general partner Vijay Pande sits down with Dr. Eric Topol, founder and director of the Scripps Research Translational Institute and one of the most cited researchers in medicine, to explore the cutting edge of preventive healthcare and longevity science.
Drawing from his new book Super Agers: An Evidence-Based Path to Longevity, Topol breaks down why understanding the biology of aging—not reversing it—is the key to preventing the “Big Three” age-related diseases: cancer, cardiovascular disease, and neurodegenerative conditions. The conversation spans AI-powered risk prediction, organ clocks, polygenic risk scores, GLP-1s, and the cultural and economic shifts required to move from a “sick care” system to one rooted in precision prevention and extended healthspan.
If you’ve ever wondered how data, personalized medicine, and AI can add seven healthy years to your life—and what it will take to bring those benefits to everyone—this episode is for you.
Resources:
Find Eric on X: https://x.com/erictopol
Find Vijay on X: https://x.com/vijaypande
Stay Updated:
Let us know what you think: https://ratethispodcast.com/a16z
Find a16z on Twitter: https://twitter.com/a16z
Find a16z on LinkedIn: https://www.linkedin.com/company/a16z
Subscribe on your favorite podcast app: https://a16z.simplecast.com/
Follow our host: https://twitter.com/stephsmithio
Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.