Ageless: The New Science of Getting Older Without Getting Old

become a sustaining member of the commonwealth  club for just 10 a month join today greetings i'm dr robert lee kilpatrick the chair  of the health and medicine member led forum here   at the commonwealth club of california and i'm  delighted to welcome you to what promises to be   a fascinating program today focused on a topic  of interest to all of us that is to say aging so   we have today uh the author of a new book called  ageless the new science of getting older without   getting old and dr andrew steele is joining  us all the way from the united kingdom   he uh got a phd in physics at the university  of oxford and then he realized that aging was   the most important scientific challenge of our  time and he switched to computational biology   so he's written this wonderful book and dr steele  is a full-time science writer and presenter   so uh i'd like to welcome you uh andrew to the  commonwealth club of california let's go and let's   hear about the science of aging fantastic thank  you for that introduction and thanks very much   everybody for coming along and thanks for having  me um what i thought i'd do before we started is   just give a little bit of an introduction to who i  am uh robbie's already started doing that uh just   then by telling you that i started out actually  as a physicist and ended up moving into first as   a working as a computational biologist and then  decided to make this another sideways jump in my   career to becoming a full-time science writer  and presenter and i'm going to give you a bit   of a flavor as to why that was throughout the  talk actually i'm going to show you i'm going   to spend quite a bit of time dwelling on actually  the graph that changed my career because um you   know i i toward the end of my phd in physics  started reading about these exciting results in   aging biology and i decided it's just the most  important scientific challenge of our time but   also uh the case i make in the book is the most  important humanitarian challenge of our time so of   course this is uh the cover of my book ageless the  new science of getting older without getting old   and the key thesis behind it is that aging  is this enormous humanitarian challenge it's   something that a lot of us i think just consider  an inevitable part of you know the human condition   but actually i really want to sort of expose it  for what it is it's this enormous humanitarian   problem and i think you know because people think  it's so inevitable they're often blind to the   incredible developments in biology that have been  happening in the last sort of 10 20 years that   have really shown us that aging isn't inevitable  at all we've actually got dozens of different ways   in the lab at least to slow down and even reverse  that process and we've got loads of examples of   animals throughout the animal kingdom that age  in very very different ways to human beings and   what that means is we've got on the one hand this  most enormous humanitarian challenge all of these   people growing old and all the problems associated  with it now on the other hand we've got this   incredible scientific revolution that's underway  that's giving us the scientific tools to rise   to that challenge and it's that combination it's  really really sort of thrilled me as a physicist   you know looking around to try and work out how  you can have the biggest impact of this career   and uh that means i think that ultimately i  think the idea of treating aging is going to   be the biggest revolution in medicine since the  discovery of antibiotics and i'll explain a bit   more about why that is as we go through the talk  but i'm going to start out by showing you this   uh this this incredibly significant graph at  least a significant graph to me that changed   me from physics to biology it's actually a very  simple graph you've got along the bottom here is   how old you are and then moving up the side we've  got your um chance of death in that given year and   obviously everyone knows that the older you are  the more likely you are to die but just how much   more likely really surprised me so without further  ado that is the curve in question i think the best   way to make sense of this incredible rise in death  is just to go through some of the numbers and talk   about what they mean so if you look at the very  left hand end of the graph there if you're aged   zero and this graph is for people who are born  in uh you know fortunate enough to be born in   the richer parts of the world then you've got  about a point five percent chance of not making   your first birthday and that's because you could  be born in some kind of congenital problem you   could you know develop a very very young age  cancer you could die of an infectious disease   before your immune system has fully had time to  develop and that means about one in 200 babies   don't make it to their first birthday but actually  your odds of death go on uh improving or i should   say you know your odds of death gone decreasing  which is obviously an improvement uh throughout   your childhood and by the age of 10 you reach  this point at which you have an incredible title   current ten-year-olds are the safest human beings  in the history of our species they've got a less   than one in ten thousand charts of dying in that  year and i think that's just remarkable just you   know think about quite how unlikely ten-year-olds  are to die you know quite how robust those tiny   little bodies really are but unfortunately of  course looking at this graph it's all downhill or   rather on this graph uphill from there our chance  of death just goes on increasing from that sort   of miraculous age of 10. so by the time you're  18 you've got about one in 3 000 chance of death   if you're in your 30s like me your odds of chance  sorry your odds of death in any given year are   somewhere in the region of why in a thousand and  it's worth thinking for a moment about just what   that actually means if my odds of death were to be  able to continue at roughly one in a thousand for   the rest of my life i'd live into my thousand and  thirties on average you know because weighing a   thousand yards of death every year is eventually  going to catch up with me but probably not for   another 10 centuries time and that's absolutely  amazing because you know maybe it's not quite as   safe as a 10 year old but it's really remarkable  that bodies of people in their 20s their 30s even   their 40s are in this you know such an exquisitely  balanced state that the chances of them sort of   falling off the tightrope of life in one direction  or the other in a sufficiently major way that   they end up dying it's just incredibly slim but  unfortunately um the problem with uh human sort of   risk of death is that it starts to increase pretty  rapidly and in fact it's an exponential increase   and we've all seen over the course of the last  18 months with the pandemic quite how significant   exponential increase can be it starts out very  small perhaps there's a very great deal of change   but suddenly it can become very big very quickly  and actually our chance of death as human beings   doubles about every eight years and what that  means is it starts out as you know say why in   a thousand in your 30s by the time you're 65  your odds of death are about one percent you   know you won't make your 66th birthday and again  those actually aren't terrible odds if that were   to continue for the rest of your days you'd live  to 165 on average but clearly that isn't the case   and actually by the time you've got a risk of  death of one percent one in a year then that's   a big enough number that doubling it starts  to you know become quite a significant factor   so if you're lucky enough to make it to the age  of 80 your odds of not making 2 81 or about 1 in   20 somewhere around 5 and if you're lucky enough  to make it into your 90s which is obviously off   the top of this graph here then your risk of  death in one of those years is about one in six   and that's life and death at the role of a  dice it's just this incredible increase in   mortality from you back in the glory days when  you're 10 years old so there are a couple of   different ways that you can look at this graph  and the first is as a human being you know you   can look at this and it's a bit terrifying frankly  you've got this exponential wall of mortality sort   of coming towards you at this inexorable pace of  one year per year but as a scientist you know as   a physicist coming to the end of his phd there's  a really fascinating question that this graph sort   of represents and that question is given that  human beings have this incredibly consistent   and incredibly rapid increase in risk of death  a certain moment in their lives and depending on   where you draw the line in their 60s or 70s or 80s  their risk of death really goes up very suddenly   and this happens you know across uh different  populations across humans all across the world   why is it you know what is it in  our biology what fundamental process   is driving this incredible increase in risk  of death and that's the sort of big scientific   question in order to get to the bottom of that  scientific question we're going to have to ask a   uh the obvious question what is this  process well it's aging so what is aging   well when you mention aging to most people they  think of a few different things uh one idea   is do you think of the obvious cosmetic science i  think that's the thing that springs to most of our   minds you know things like the wrinkles the gray  hair the hair loss particularly if you're a man   these are the obvious external factors and things  that are going on on the outside of our bodies   and what these things happening on the outside of  our bodies really reflect is what's going on on   the inside and the thing that really scares me as  a biologist and you know thinking about this from   a medical point of view is the increase in risk of  diseases things like cancer heart disease stroke   and dementia they're the four biggest killers  in the modern world and you know this this risk   of disease just goes on increasing and increasing  it's the aging process the slow steady biological   changes that are happening inside your body that  primarily drive that increase you know you can   smoke you can drink you can eat badly you cannot  get enough exercise there are loads of things you   can do that can have a negative impact on your  health but at the end of the day none of them is   as significant as this sort of unavoidable process  of merely getting older you can be a chain smoking   heavy drinking you know overweight 30 year  old and in terms of risk of disease at least   you're in a better state than a perfectly clean  living healthy you know normal way 80 year old   so clearly there's something happening in our  biology there then there's other stuff that   some of which we call diseases some of which we  call uh we don't call disease we want you know   labels things like frailty or other kinds of loss  primarily it's what i've called these different   things loss of vision loss of hearing loss of  muscle mass and that kind of thing and what this   umbrella really covers you know it's not the loss  necessarily of those specific sensors or faculties   it's the loss of your independence it's the  loss of the ability to you know get on with   your hobbies to play with your grandkids  to even you know potentially get around the   house as you get later into the stages of these  things and that i think is why aging is really   this humanitarian problem because it isn't just  about dying it's about all the various you know   unfortunate things that can happen you're on the  way to that cause of death and then finally there   are the things that aren't necessarily strictly  sort of aging per se but they're things that are   made much worse by the process of getting older  these are things like infections and injuries   stuff that we shrug off as a younger person but  can be massively massively significant if you   have one of these things happen to you when you're  a bit older so take the example of breaking a bone   if you're a young person you break a bone you know  you go to hospital you have it set you might have   a plaster cast put on and then you know you stick  around in that plaster cast right you know maybe a   few weeks maybe a month or two if it's if it's  a bad break but basically you shrug it off you   heal you get better but if you're an older  person you break a bone a really common bone   to break is your hip you can end up in hospital  for an incredibly extended period of time you're   lying down in bed for a huge amount of time so  you lose a lot of muscle mass you could contract   a hospital acquired infection a break of a bone  for an older person can be the end of their life   and even if it doesn't ultimately result in them  dying it can be an enormous change because you   know you come out of hospital you've lost all that  muscle mass you're much less able to get around   and that means you know you can't engage in  exercise you can't do the things that keep   you healthy and so it can be a real start of a  spiral of decline so this is the sort of panoply   of different things that happen to us as we age  from you know wrinkles and gray hair to various   different diseases to various different kinds of  loss and fundamentally you know this is what is   underlying this graph that i showed you back at  the beginning of the talk um you know the reason   that things are carrying on increasing the reason  our risk of death increases is because of this   smorgasbord of suffering and actually what's  causing the deaths directly is those diseases   so if we look at a very similar graph but we've  still got ages on the bottom obviously by the side   instead of chance of death we've got your chance  of coming down with a particular disease we can   look at the lines for cancer heart disease stroke  dementia and what you can see is that all of these   follow that same sort of terrifying exponential  pattern dementia is a really good example   actually because it's almost unheard of in people  underneath under the age of 60. so you know people   unless you've got a genetic free disposition a  particular mutation that causes you to get what's   called early onset dementia almost nobody gets  it before their 60s but then actually after that   point the risk of dementia doubles every four or  five years so faster even than the risk of death   itself and it's you know the combination of these  different things these are basically what kills   you so this is why our risk of death increases  exponentially it's because the risk of these   diseases is increasing exponentially to give you  another example this disgusting mucousy green line   here is uh the risk of getting a chest infection  this isn't just a cough or a sniffles and it gets   nice and deep down into your lungs and can can  lay pretty low for a while and what you can see is   that even in you know sort of your your prime even  in your your youth you've still got a one or two   percent chance of getting a chest infection every  year it's not something that's totally unheard of   but you can see that at either end of  life either when you're very young and   you haven't got a fully developed immune system  and your body's just a bit less resilient overall   or as you get older and your body and your immune  system are starting to weaken your odds of getting   all of these things and in fact the odds of  them becoming serious are much much greater   and of course you know chest infections aren't  making such big news at the moment as the thing   that's really in the news all over the place  the coronavirus pandemic so just to give you one   more example of this again age and years and then  your chance of death if you contract coronavirus   it looks like this it's another terrifying  exponential graph that doubles faster than the   risk of death itself in fact you know if you catch  coronavirus in your 80s you are literally hundreds   of times more likely than someone in their 30s to  die of the disease and that's because of this you   know whole range of factors not just the weakness  of the weakening of the immune system but also   the reduction in what's called reserve you know  sort of the reserve that your body has to fight   off various different insults be that you know a  hip injury or be that a coronavirus now obviously   this has changed dramatically now because most  people in the us and the uk and some of the richer   parts of the world have already been vaccinated  especially if they're in those older age groups   and so that obviously transforms what this  curve looks like but before those vaccinations   came into play clearly aging was a huge huge  driver of you know the deaths in the pandemic   so i think looking at this graph there's  something that this graph really explodes a myth   i think there's this there's this sort of  pervasive myth you can die of old age and the sort   of way that's visualized is that you're you know  you're old you're wrinkly you've got gray hair so   you've got these cosmetic signs you go to bed one  night you know you're basically fit and healthy   maybe you're a bit slower than you were but  then painlessly you just don't wake up the next   morning but that is almost never the case it's  not to say it never happens it's very very rare   most of the ways that people who are  older die are of one of these diseases   and most of the ways that these diseases kill  you they're slow they're drawn out you know if   you die of heart disease a few people if they're  quite lucky i guess you could look at it that way   just suddenly have a heart attack and you know  in the middle hopefully of an enjoyable activity   and keel over dead but actually mostly  heart disease is a progressive condition   it does indeed sap away your independence  it reduces your ability to exercise then   you know as i say play with your grandkids and  eventually can get severe enough that you can't   climb the stairs without being incredibly out  of breath and so on and so on so it really does   have this huge effect on quality of life and the  treatments can be grueling too if you think about   chemo or radiotherapy for cancer these things can  take years to finally kill you and they do so in   this variety of fairly unpleasant ways if you  think about the average 80 year old they have   five different diagnoses uh you know things that  are wrong with them basically and they're taking   an average of five different medications in  order to deal with those problems so you know   this isn't just a picture of health that you  can then suddenly fall off the end of a cliff   this is really caused by all of those diseases so  back to my favorite graph uh just uh you know one   more time this is as i say a graph that did change  my career so you'll forgive me for showing showing   it to you quite often the last thing that you  might think looking at this graph is that this   is something that we in the wealthy parts of the  world are sort of perversely lucky enough to have   we're lucky enough to live long enough  that we get a significant way up this curve   and what that means is that we can suffer  from the degenerative diseases of aging   now in the pre-zoom era what i would normally  have done is done a quiz because this   and the quizzes you know you can do this at home  you know i can't get you to stick your hands up   and tell me what you think the answer is just uh  think in your head how old do you think the global   life expectancy is so how long do you think the  average person on planet earth lives not just   the rich countries but all of the countries on  the in the world average together and the reason   i like to do this as a quiz is because um if you  do surveys if you look at the survey data on this   people wildly underestimate how long uh people  around the world are living we we tend to estimate   it by 10 maybe even 20 years and the reason is  i think a lot of us were taught at school that   there's a very large developing world you know  poor parts of the world where they have less   healthcare less sanitation worse food everything  about these countries is impoverished basically   and so we imagine they've got much much shorter  lifespans as a result but actually the sort of   double-edged sword the good news and the bad news  i'm going to put you out of your misery now is   that the most recent value we have for global life  expectancy back in 2019 72.6 years old and that's   because a lot of those developing countries have  really really rapidly accelerated through these   changes in life expectancy in the last 50 years or  so and they're really snapping at our heels now in   the rich world and that means that most people in  most countries are living long enough to grow old   now as i said this is sort of a double-edged sword  because on the one hand this is fantastic news it   means people in all most countries in the world  are living longer healthier lives than ever before   but on the other side of the coin as someone  who's you know obviously interested in aging   it means that most people in most countries are  living long enough to suffer from the cancer   the heart disease and dementia and a lot of the  people who are doing that in poorer countries are   doing so in places where the healthcare systems  just aren't set up to deal with these chronic   diseases of aging so it's an even bigger problem  potentially being stored up in the poor world than   in the richer parts of the world so if we were to  aggregate this together the bad news is that um   if you look at the 150 000 people who die every  single day on planet earth every single one of   these little uh stick figures is uh represents a  thousand humans then over two-thirds of them more   than a hundred thousand people a day are killed  by aging by the cancer by the dementia and so on   that means that aging is responsible for by far  the majority of deaths as i hope i've really   illustrated to you in the last few minutes of  the talk um this isn't just you know people dying   although death is a nice easy statistic it's  very unambiguous whether someone's dead or not   what these represent is a huge quantity of  suffering it's millions billions of people   gradually deteriorating over decades getting these  horrible diseases you know suffering along the way   to the along the path to death so this could be  a pretty depressing book pretty depressing first   part of a talk what is it that we can do about it  well i promise this is the last time i'm going to   show you my favorite graph as i said humans  risk of death doubles about every eight years   but this is not a universal throughout the animal  kingdom and actually this is an animal that   really doesn't display that property this  is something called a hydra it's about a   centimetre long it's a little pond creature and  its risk of death if you observe it looks a bit   more like this now obviously we haven't gone all  the way through to do this experiment we think   their risk of death stays approximately constant  at about point two percent every single year   and that's incredible because it means that if you  extrapolate that outwards as i say we haven't had   the time effectively this experiment but about ten  percent of the hydra would still be alive after   a thousand years which is just a phenomenal  lifespan for this incredibly simple organism   but what's more more important and more exciting  than the fact they could live a thousand years is   that they have a property called negligible  senescence so this um you know senescence   is just a biological word for getting older  negligible obviously just means not much of it   so they don't get old their risk of death is flat  as a function of time and that means they in this   very statistical sense at least don't age they  you know have a set the same risk of death the   same risk of you know hydra diseases throughout  their lives and that's something you know given   that hydra can do it why can't humans do it too  could we work out a way to be a bit more hydra   now you might be looking at that and thinking come  on andrew and this centimetre long pond creature   it's got a handful of cells you've got trillions  of cells we're a much more complicated thing how   on earth could we possibly hope to emulate this  little creature's ideas you know in our own   biology and obviously it's not quite going to be  as simple as transplanting a few hydra immortality   genes and you know sorting our biology out that  way but although the hydra is still one of the   most spectacular examples there are some other  creatures that do this as well this is a beautiful   ambassador i think for the idea of negligible  senescence for the idea of aging well even though   you might not think that they look like it this is  a galapagos tortoise they're wrinkled they hobble   along at an incredibly slow speed even in youth  but the galapagos taught us uh the reason there's   this is actually on the cover of the uk version  of my book and the reason there's a tortoise or a   turtle on on the covers of the books is that they  too have this negligible senescence property the   galapagos tortoise we think has a maximum lifespan  of somewhere in the region of 170 180 years   um what's most exciting again isn't how long  these tortoises live it's the fact that they   do so without seemingly aging they have a risk  of death that's basically constant with time in   adulthood and not only you know the hydra you  can say it's risk of death is relatively constant   but the tortoises you can observe they don't  become more frail they can still they're still   just as sprightly when they're aged 150 as  they are when they're aged 30. which is to   say obviously not very strikes rightly they are  tortoises but you know they're still getting   about they're still engaging in their daily  activities they're still reproductively active   there's um the oldest tortoise in the world  at the moment is a guy called jonathan he's   actually a slightly different uh species of  tortoise but he's living on an island called   helena and there was an article that i  read in uh from a newspaper a few years   ago saying that he still likes to get on with  the ladies so he's still living a very full life   um you know and what happens is you know these  tortoises do die eventually this is harriet um   a galapagos tortoise the oldest one that's  on record she died aged 177 of a heart attack   but she just died 100 years later than a human  would have a heart attack and so i think that's   something that we can very much aspire to and they  are you know much much closer to us evolutionarily   speaking than a hydra is and again you might  be thinking tortoises they're quite different   they're cold blooded you know they're much slower  moving maybe they just live more slowly than we do   but another example of an animal that has an  incredible lifespan compared to its size at least   is this little thing now you might be thinking  andrew that's a penis with teeth it's actually   an animal called a naked mole rat and these  are some of the most incredible uh long-lived   animals that we have that we've we've uncovered  so far it's about the size of a rat or a mouse   and a rat or a mouse can live you know maybe two  maybe three maybe four years on the outside in   the lab and yet these little things can live into  their 30s and most importantly even though they   look incredibly wrinkly again it seems that all of  these ambassadors for negligible senescence have   you know they're not the most beautiful uh  beautiful beautiful creatures but nonetheless   these animals appear to be negligibly senescent  in the sense of not becoming frail they stay   reproductively active as i was already mentioning  you know they stay cognitively active throughout   their lives so this really is it's a mammal it's  much much more similar to us than a hydra or   tortoises so the question is how can we be more  naked mole rat another thing i'd just like to   mention about these things is that they're almost  cancer-proof we actually thought it was impossible   for a naked mole right to get cancer until we  started studying larger and larger colonies of   them and found a handful of these creatures that  actually had the disease but nonetheless you know   it's much much rarer for these things  to get cancer than it is for humans to   even though where um even though they live such  an incredibly long time for their size so the   question is you know how can we be more naked more  about how can we be more hydra as human beings how   can we reduce our risk of death and come back  to try and be more neglected to be senescent and   so i'm going to return to this question what is  aging and what i'd like to tell you is that you   know this slide i showed you before although it's  perhaps an intuitive conception of what aging is   it's really a cheat because actually everything  on this slide that i've shown you is you know   a massive broad category i mean take cancer  there are hundreds of different kinds of cancer   if you take memory loss there are just so many  different diverse ways that you can lose your   memory there are different kinds of dementia  there are different processes that go on that   you know we wouldn't necessarily go as far as to  call dementia that can cause cognitive decline   happening at many different scales inside  your body you know some of it's going on   inside cells somebody's going between cells  some of it affects the blood vessels in your   brain all of these different ways that you can  you know lose cognitive function as time goes by   so this this slide is really very much a cheat  and actually although it's a cheat i think   it really illustrates the the methodology with  which we approach these age-related problems   we approach them often medically in silos so if  you you know find a lump on your body somewhere   you go to your gp and they tell you oh that looks  a bit serious we have to send you to an oncologist   a cancer doctor they'll then take a look they  take a biopsy they find out it actually is cancer   they'll give you chemotherapy or radiotherapy they  might operate on it to try and remove the lump   and so on and so on but this is all very focused  on your cancer care and doesn't really consider   the fact that most people who get cancer are old  themselves they've already got a variety of other   problems they're becoming frail they might have  a heart condition that's sort of brewing in the   works even if it isn't their primary uh cause  of concern at that particular moment in time   and we treat all of these things very much  on an individual basis and we often treat   them quite uh sort of palliatively rather than  addressing the root cause so you know if you've   got something like muscle loss sometimes you  might be prescribed some physiotherapy even   that's you know unusual you're more likely to be  given a walking stick and so we try and paper over   these things rather than actually trying to attack  the fundamental root causes so what is aging well   actually if you ask an aging biologist you get a  list a little bit more like this and don't worry   about reading every single one of those things  you know there's ten of them and some other   some of the words are quite sciency though i will  explain the relevant ones you know what they mean   and you'll be relieved to hear i'm not going to  go through all of these in the rest of the talk   what's really exciting about this is these other  10 what are called hallmarks of the aging process   and these are the hallmarks i go through in the  book um there that's actually adapted from a 2013   paper of the same name called the hallmarks of  aging they only had nine there's been a bit of   intervening science i jiggle things around a  bit added an extra one and ended up coming up   with ten for a variety of sort of scientific and  narrative reasons but what's really exciting about   these ten hallmarks is that these although they  are categories you know there are still various   different for example talking about stem cell  therapy there are various different populations   of stem cells in your body that might need therapy  they're much much smaller categories than cancer   and each of these causes each of these hallmarks  drives a multitude of age-related diseases so a   variety of different things are caused by these  individual hallmarks to try and make this all a   bit less abstract what i'd like to do is show you  um firstly you know what these are and secondly   how we could think about potentially treating them  and preventing this range of age-related problems   just by going through a couple of examples and the  first one i'm going to talk about is telomeres and   one of the reasons i'm going to talk about this  is this is a very common question you get when   you know you tell people you're working on a book  on aging biology because they've often you know   heard of this this is something that was really  really big news in this or late 90s early 2000s   telomeres an enzyme called telomerase so how is it  that these things affect uh you know the course of   aging and can affect a range of different  diseases well let's have a look at what a   telomere looks like on the microscopic level this  is a picture of what you might see if you were to   zoom in very very deep into one of your cells  and look in the nucleus the part of your cell   that contains the dna each of these blue things  is a chromosome so it's a particular length of dna   and then on the ends of the chromosomes you  have these little green and red fluorescent   markers they're called so the scientists have made  these uh little bits of dna glow and these are the   telomeres they're the caps on the end of that  dna so the normal dna is bundled up into these   chromosomes they're the individual lengths at  the ends of those lengths you have the telomeres   and if we were to zoom in even further and to  take rather than a sort of microscope view a   sort of chemical view dna is made up of four bases  chemical letters effectively a t c and g and these   letters are arranged you know that they're the  code by which life is written but if you uh zoom   in on a telomere what you'd see is this pattern  just repeated effectively nonsense tta ggg tta   ggg tta ggg hundreds or even thousands of times  as far as the eye can see and so you've got to   wonder you know why is it that i chromosomes these  beautiful intricate information dense you know   huge packets of genes and information how your  cells should work the instruction manual for life   why is it that they're capped with this  endless repeated nonsense and the reason   is the evolution actually created telomeres to  solve a couple of rather ridiculous problems   so there are two issues here the first is  that when evolution when when your cell spots   a loose bit of dna flailing around inside one  of your cells it thinks there's a problem there   and the reason is that loose dna probably means  that you might have started with a continuous   strand of dna and if that continuous strand  breaks then the body needs to quickly glue   those two pieces back together again to make sure  there aren't any problems and that means you've   got these things called double strand repair  enzymes that can go in and grab those things   and stick them back together again basically so  if you just had an end of a chromosome which is an   entirely natural piece of sort of loose flailing  dna flailing about the place then your body would   fuse them all into one massive megachromosome  and it would cause you know basically dna chaos   and so in order to avert that your body creates  these telomeres these lengths of repeated sections   and then there are other proteins that can go and  stick onto these repeated sections and basically   protect it and the analogy that's sometimes given  is they're a bit like the caps on the end of your   shoelaces um that um you know that protect them  from fraying and that's you know fraying they   protect them from the the cell aberrantly sticking  them back together the other problem and the one   that's probably more relevant for aging is that  when your cells divide they have to copy that   dna because it means that both daughter cells have  to have a copy of that instruction manual in order   to go about their business and when those copies  are made um there's a strange strange problem that   evolution hasn't managed to solve in in other than  rather a stupid way which i'll explain in a second   so the problem is that when um your dna is copied  the dna copying enzymes chug along along the dna   and they they you know produce these astcs  and g's in order to precisely copy the dna   but then when they get to the end they can't quite  make it all the way to the end of a chromosome   and you can imagine this like a builder who's  going along standing on top of the wall that she's   adding bricks to and when she gets to the very  final brick she can't add that final brick because   she's already standing there she's in her own way  and that means that you know you effectively lose   a brick at the end of the wall every time the wall  is copied and that exact same thing happens in or   a sort of related thing happens inside our dna  when that's being reproduced as our cells divide   so evolution could have come up with a much clever  dna repair uh sorry dna copying enzyme that could   nonetheless get all the way to the end of the dna  or it could do what it has done and just add bunch   of a bunch of repeated nonsense on the end of our  chromosomes so if you lose a little bit of that   every time a cell divides you know it just doesn't  really matter from an evolutionary point of view   there's no important genetic information stored  inside your telomeres and so if you just lop off   you know 10 or 100 bases every time a cell cell  divides it doesn't really matter and so there's   no serious consequences for the cell so that's  why evolution came up with the idea of telomeres   but you can start to see from that already how  this might be a cause of aging because every time   your cells divide your telomeres get shorter and  there's going to come a point where you're going   to run out of telomere so the question is what do  telomeres look like as you age and this is another   graph we've got age along the bottom and we've got  your length of your telomeres in bases so in dna   letters up the side and if we stick some data onto  this graph you can see it looks a little bit like   that there's definitely a correlation as in you  know there's a relationship between how old you   are and the length of your telomeres but it's  not a fantastically strong correlation and you   can see you know looking at this graph the spread  is really really wide and in fact there are some   unlucky 20 year olds who have telomeres from  similar lengths to some lucky 90 year olds and   clearly you know there's also some some strange  artifacts in the data because otherwise who is   this person are they telling me a wolverine how  have they got these incredible telomeres at you   know this age in their life it's not a perfect  marker by any stretch however if you actually   do you know do some maths and try and plot a  straight line there is as i said a correlation   and it looks like telomeres go down by on average  20 um bases 20 dna letters per year of adult life   and so that you know that's that's the sort  of starting point and as i said there's this   suggestion that it could be a cause of aging one  of the other things that sort of is a smoking gun   to blame telomeres is that people who are of  a particular age but have shorter telomeres   than average for that age are increased risk  of various age-related diseases they can be   increased risk of death so clearly having shorter  telomeres appears to be a bad thing even though   it's not um not super clear it's not this sort  of perfect correlation it's not a clock sort of   ticking fantastically accurately down to your  demise there's clearly something going on here   now what happened is that you know we discovered  the telomeres were getting shorter and the   question is there are way that we can lengthen  telomeres and of course there is a way that we   can let them tell them is it's an enzyme called  telomerase this was discovered um back in the   sort of 1980s and 1990s it was um actually the  discoverers were awarded the nobel prize it's   a really significant discovery and the idea is  that telomerase is simply an enzyme that can go   and add more of these repeats onto the end of your  dna you know so they can extend those telomeres   and that's really really important in certain  parts of your body because if you think about   you know for example in an egg cell when the  when the egg in the sperm fuse you're going to   have a new baby you're going to need to extend  those telomeres because that egg cell is going   to have that fertilized egg is going to divide  a lot of times to turn into a whole adult human   so you know telomerase comes on extends  those telomeres and keeps you know   keeps the telomeres long enough that we can have  we can have babies she can have new life however   in most adult cells telomerase is deactivated  and having you know just heard what i've told   you that um that your telomeres get shorter  with every cell division and therefore that   gets they get shorter and shorter throughout your  life and that predisposes you to disease you might   be thinking well that seems like a stupid idea why  is evolution turned off this really important gene   in most of our cells for most of our adult  life and the reason is that it's trying to   prevent cancer so let's think about what cancer is  cancer is essentially a disease where cells divide   and divide and divide indefinitely without ever  stopping and so you know the way that that works   as a cell gains a certain combination of mutations  a certain combination of mistakes in its dna   that turn off genes that tell the cells to stop  dividing they turn on genes to tell it to go go go   and that combination of genes allows the cell  to get you know to divide and divide and divide   eventually you can get big enough to form a tumor  that tube might then be able to metastasize to   spread around your body and that's ultimately the  way that cancer kills you by just dividing and   dividing indefinitely even though that's obviously  not a benefit to the body as a whole those cells   you know are sort of benefiting in a weird uh and  rather unpleasant way for the rest of the body   so that's what cancer is so telomeres are quite  a good cancer prevention mechanism because if   you notice that a cell has got what's called  critically short telomeres you know it's obviously   divided a lot of times you could tell that cell  oh you know you've divided a lot of times now mate   i think you know you're looking you're looking  at risk of becoming cancerous and the cell can   either commit self-suicide in a process called  apoptosis or it can stop dividing it can enter   a state called cellular senescence i remember  senescence i said it was just the scientific   word for aged so sort of aged cells um and hold  that thought because we're going to come back to   that as another hallmark of aging in a moment um  and therefore you know these cells stop dividing   and that seems to be you know that stops cancer in  its tracks so one of the things that cancer has to   do in order to manifest in your body is it has  to turn that telomerase gene back on so that's   how you know that's worthless or prerequisites  that cancer has to tick in order to in order to   be able to divide an indefinite number of times  so obviously other stuff needs to go wrong to   make cancer happen as well but this is just like  i say one sort of box that cancer has to tick   so back in the early 2000s telomeres had been  discovered telomerase had been discovered   and scientists were wondering what happens if you  give mice an extra copy of telomerase which builds   up their telomeres and the result basically was  cancer and actually you know that really popped   the telomeres and telomerase bubble for a long  time because it seemed that well exactly as i've   sort of just warned you about us for a long time  sort of warning you about on the previous slide   um activating telomerase increases the risk of  cancer it doesn't actually cause cancer as such   but it pre-ticks a box on cancer's list and it  meant the mice are at much much greater risk of   cancer it didn't extend their lifespan you know  it seemed to basically just be a bad thing and   as i say this really really you know burst the  bubble it caught on i think both in scientific   and popular circles because in the late 90s  there was a lot of buzz i remember you know   when i was um when i was still at school watching  documentaries about how i've discovered telomerase   it's the fountain of youth we're going to all  be living forever as a result of turning this   into some kind of human treatment and then the  wonderful cynical narrative comes and overpowers   that and says you know telomerase right it's not  all that because actually it's a huge cancer risk   so that basically you know seemed to put a stop  to all of that but thankfully some scientists   persisted they sort of continued to believe in  telomerase and some more recent results have made   us more optimistic that this might be something  that we can uh do to try and alleviate our own   aging one of the first experiments was in 2008 and  uh mice were given an extra copy of various genes   not just telomerase here but also these three  genes are not going to go into detail about what   they do they're basically anti-cancer genes they  make cells more likely to commit suicide or go   senescent if they're at risk of becoming cancerous  and what they found was that by giving telomerase   with anti-cancer genes you actually got a 40  increase in lifespan for the mice that were given   this cocktail and no extra cancer above you know  mice that hadn't been given this cocktail of genes   so it shows that you know maybe naively  intervening in biology just going in and turning   on telomerase isn't isn't sufficient to extend  lifespan because evolution is often quite clever   however we can be cleverer than evolution if we  make even you know a small number of additional   changes if we try and offset that known cancer  risk by giving some anti-cancer genes we can   extend the lifespan of mice and then in 2012  there was a treatment given that was i think   slightly more exciting for humans because um  obviously we aren't all fortunate enough to have   been born with a bunch of genetic modifications  what happened here is that adult mice aged about   a year and that's something like maybe 40 human  years old because obviously mice have much shorter   lifespans than humans do so mice in middle age  basically were given an injection of temporary   telomerase a gene therapy that activated  the telomerase temporarily extended those   telomeres but didn't give it permanent activation  which is something that might be handy for cancer   and what they found was that those mice lived  about 20 percent longer and they again didn't   seem to get any additional cancer compared  to control mice in the experiment so um and   i should say not only this this isn't just about  lifespan um they also had higher bone density and   i think one thing i find most entertaining about  reading mouse papers especially as a computational   biologist who never dealt with them in the lab  is the variety of different uh interesting tests   they had to subject their mice to to demonstrate  whether they're aging faster or slowly or not   these mice are actually better at walking a  tightrope as well so you know that's sort of   an indication that they're less frail they've got  a better sense of balance and so on so it seems   that this telomerase therapy could potentially  alleviate aging uh certainly alleviates aging   in mice and could potentially you know be  something that we think about using in humans   so back to this list of hallmarks um i've just  described the idea of using telomerase to try   and increase the length of our telomeres and try  and reduce their reduce their reduction in length   with age another really exciting idea is this  idea of doing something about senescent cells   and i've already actually given you a bit of a  hint about senescent cells now these cells that   have divided too many times um another way that  they can become senescent is they might have a bit   of dna damage that um that then uh makes your  body think they're about to become cancerous   and so again your body will put on the brakes  and stop them from dividing the problem is that   when a cell becomes senescent it starts  emitting this cocktail of toxic molecules   and that might seem like a bit of a strange thing  for ourselves to do you know why is it polluting   its environment with this with this horrible stuff  the answer is that they're they're not toxic as   long as they're only turned on for a short time  what they basically are is they're distress flares   they're saying hey i'm over here i'm a cell i've  gone senescent um can you please come and clear me   up and they're calling out to the immune system to  come and to come and gobble them up and in youth   that is exactly what happens our immune systems  are attracted over rapidly they destroy these   senescent cells and you know basically the cycle  of life continues inside our bodies unfortunately   as we age these cells seem to accumulate and the  reasons for that are firstly they're produced more   commonly as we get older so if you think about um  you know you're older your cells have divided more   times they've had more opportunities to get dna  damage so all the processes that cause senescence   are increasing and you know accumulating with time  then on the other side the balance your immune   system which is normally what clears these cells  up is getting weaker it's becoming uh immunosine   essence we call it and actually ironically some  of that is caused by the immune cells themselves   becoming senescent so it's this sort of vicious  circle that causes senescent cells to build up   so as they pump out these molecules they aren't  just calling over the immune system they're also   driving a process called chronic inflammation  which effectively accelerates the aging process   now um this you know this this is therefore  clearly a candidate for a hallmark of aging the   thing that's the most convincing evidence is that  we can actually give drugs to mice now that remove   their senescent cells and leave the rest of the  cells in their body intact these are drugs called   synalytics and what uh scientists did in 2015 they  gave some of these drugs to mice aged 24 months   i've already mentioned that mice obviously age  more quickly than we do 24 months is about 70 in   human years these are you know pretty pretty old  mice give them these analytics they basically get   biologically younger so the first thing to say is  they live a little bit longer maybe a few months   which is perhaps a few years in human terms um but  they don't just sort of stagger on in geriatric   ill health these mice are they're they're they're  healthier as i say younger for longer they um   they get they get less cancer they get less heart  disease they get fewer cataracts so a whole range   of diseases is prevented um they're less frail  they can run further and faster on a little mousy   treadmill they're using this experiment i told  you that mice have these this sort of bizarre and   wonderful gymnasium of different ways that they  can test how old they are they're more curious   so it seems to have a cognitive decline as well  because if you put an old mouse in a maze it tends   to be a bit more anxious and less exploratory than  a younger mouse is but these analytics rejuvenate   some of that curiosity and honestly these animals  they just look great they've got better fur   they've got plumper thicker skin as i said i'm a  computational biologist i'm not used to dealing   with mice and it's just obvious that these animals  they look great so clearly senescent cells are a   fundamental driver of a whole range of different  age-related problems and by getting rid of them   we can um we can start to slow down aging even  perhaps reverse aging in a variety of different   ways and what's really exciting about this is this  isn't just something that's happening in mice in   the lab there are now 20 or 30 companies trying to  turn this analytics from sort of a lab bench idea   to something we can actually use in the clinic so  this really is an idea that we could see you know   in clinics relatively soon probably for specific  diseases at first but if these drugs are effective   and if they're safe maybe we could be using them  for the ultimate dream of anti-aging medicine   which is to try and apply these treatments  preventatively to people who haven't really   got anything quite quite wrong with them you know  people would currently consider medically healthy   but they're just old they've just been around  on the earth long enough to be susceptible   uh to age-related diseases and we give them these  analytics remove some of those senescent cells and   make them less likely to get cancer make them less  likely to get frail just make them less likely to   get ill in the first place and increase not just  their lifespans or how long they live but really   crucially increase their health span so they're  healthy amount of time they spend healthy too   okay so that's sort of a rapid introduction to  the science i've told you what aging is i've   shown you a little bit about these hallmarks  and how we might go about treating them   i thought i just finished the talk with um what  is in some ways a slightly bizarre question but   it's one that i get an awful lot which is should  we cure aging the reason i consider this bizarre   is because you know imagine i just given a talk or  written a book about cancer research the brilliant   new way that we've got to cure cancer there'll be  no one who would be in an audience of a talk like   this and stick their hand up at the end and say  but andrew you know what we're gonna do with all   these extra people aren't they gonna get bored  in their extended cancer-free lifespans aren't   we gonna cause overpopulation that's gonna crush  crush the earth um and you know i just find it   very strange that we place aging research which is  fundamentally just an extension of modern medicine   it's a way to prevent all of these diseases that  we're very happy to sort of deal with and talk   about individually we place aging research into  such a separate moral social ethical category and   so i just wanted to ask this question and i think  um even though there are a lot of ethical issues   that could be thrown up by people living longer  healthier lives it would change you know what it   means to be human it would change our societies  it would change all kinds of different things   i really do think the moral case for doing so is  absolutely watertight and i'm just going to give a   quick example and that example is the most common  question i get which is what about overpopulation   and the first thing i'd like to do is take  issue with even classifying it as overpopulation   because that implies that the people  are the problem when actually it's the   uh the richest 10 of people in the world emit  50 of the world's carbon dioxide for example   it's what we're really worried about is resource  use and that resource use is distributed very very   unevenly throughout the planet if we want to bring  those 90 of people who are only emitting the other   half of the carbon dioxide up to the same you  know level of well-being of of lifestyle we are   enjoying in the rich parts of the world then  we're already gonna have to do something very   very serious about resources even if population  wants to do anything and so i think it's much more   important to characterize this as a resource issue  rather than a population one but nonetheless it is   helpful to think about it in population terms it's  a nice easy thing to quantify so i've got a graph   here which shows you along the x-axis time and up  the y-axis you've got the population of the planet   earth in billions of people and this is sort of  the story so far um we've got something like seven   or eight billion people on the planet earth at the  moment and that population is steadily increasing   so what i thought i'd do is i'd try and work  out what would happen to the population if   we did something really serious about aging so  let's start by having a look at what we think   is going to happen anyway this is what's called  the medium variant it's the un's best projection   so best guess as to what i think is going to  happen to the population between now and 2050.   and that means that we think that by 2050 we're  going to have a population of about 9.7 billion   people at this medium variant if the assumptions  behind it turn out to be correct so when we talk   about treating aging we're potentially talking  about making people live longer and therefore   they'll be around on the earth contributing to the  population size for longer and so i thought how   can i simulate this you know i'm not a demographer  i'm certainly not a demographic modeler which is   a whole sort of specialism in itself what i'm  going to do is i'm going to make a very simple   assumption i'm going to imagine that we literally  cure death not just aging but all forms of death   in the year 2025. now that's a wildly optimistic  assumption if you think that's a piece of human   progress it's a wildly pessimistic assumption if  you're a population pessimist who's really worried   about resource use let's have a look at what that  does to the global population as you can see it   does increase it and it means by 2050 we'd have  about 11.6 billion people so almost 2 billion   more humans on the planet than we would  in the case where we didn't cure death   and that means we're potentially going to have  to work about 20 harder to solve problems like   climate change to solve problems like land use and  i think there are a variety of things to say about   this the first is you know that's not nothing it's  going to require us working harder and 20 is not   negligible however you've got to remember what's  on the other side of the balance sheet here we've   got the single biggest cause of human suffering  got two-thirds of deaths and that's you know only   going to increase the global population ages and  so i'd happily work 20 percent harder to solve all   of our environmental problems if that meant we  were going to have this huge bonus on the other   side of the balance and that we're going to be  able to reduce the amount of death and suffering   from aging from these age-related diseases from  cancer you know stop people getting dementia these   are all fantastically important goals and the most  important thing of all to say of course is this is   an absolutely ridiculous scenario this assumes  that not only do we develop these drugs by 2025   but we've got them in a form that humans can take  and we roll them out literally globally at that   moment so clearly this is a this is a wildly as  i said so optimistic stroke pessimistic scenario   given that actually the effort that's going to  need to be expended if we do do something about   aging is less than this i just don't see this as a  moral obstacle at all obviously there are loads of   other oh i was going to say that these error bands  here are just caused by changing the birth rate so   you can see that even our uncertainty about how  many how many basically how many children we're   going to have has a huge huge influence it's  almost as large as literally turning off death   so we've already got this uncertainty  sort of baked into our future population   obviously there's loads more stuff that we could  talk about um but i just wanted to give one last   example of why this is such an important idea and  that's not just the moral case but the economic   one and so i'm going to show you now is the  cost of aging to the u.s just by looking at not   the total cost of aging but the cost of my four  favorite favorites probably the wrong word but   these four most common uh killers in the modern  world these four massive age-related diseases   cancer heart disease stroke and dementia and these  rectangles show their cost to the economy not   just to healthcare but also to things like people  giving at work because they're you know either ill   themselves or they're giving at work to look after  an elderly relative who has one of these problems   and what you can see is these numbers well  they're huge they're hundreds of billions   and ultimately if you add all these things  up they come to nearly a trillion dollars um   this is obviously an underestimate of the true  cost of aging because it doesn't count a whole   load of other diseases it doesn't count frailty  it doesn't count all kinds of different stuff   but this just gives you a ballpark and then  we can compare it to um how much is spent   on aging research in the us you're lucky to  have the nia the national institute on aging   which uh looks into the you know looks into the  process of aging that little green square there   isn't just a style thing it's actually  in proportion to the size of the amount   of money that's spent it's about three and a half  billion dollars and so to compare that to the four   trillion which is the total u.s spending on  health care it's less than a thousandth of that   even though age-related diseases are a huge driver  of that healthcare spending okay so that's already   looking like quite a small amount but actually  it's even worse than that there's a running joke   in the aging biology community the nia  stands not for a national institute on aging   but national institute on alzheimer's disease  because about two of those three and a half   billion go straight to the neuroscience division  effectively looking just into dementia so that's   already you know not looking into aging is looking  to why the consequences of aging then there's   various other stuff the nia does things like  gerontology social gerontology that kind of thing   the actual aging biology division which is down  here only gets about 350 million dollars a year   that's just over a dollar per american and  that's just ridiculously small compared to the   scale of these problems and actually it's even  worse than that suggests because a lot of that   research is looking into the fundamental causes  of aging but not how to do anything about them   and obviously understanding the basic causes of  aging is really really critical if you do want   to do something about them but the amount that we  invest in actually trying to do something about   aging is just minuscule compared to the scale  of the problem that aging is trying to solve   and so this fundamentally is the reason that i  wrote this book because working as a biologist   i found that biologists weren't as familiar  as they should be with asian biology it's not   commonly taught in undergraduate lecture level  it's not commonly in textbooks my wife's a doctor   and she never had a single lecture on aging  biology during her undergrad degree and she   knows it's just not something you come across  um so we really really need to raise the profile   of this both scientists and doctors with  with ordinary people i want people to be   talking about this in bars and you know dinner  parties as soon as those are safe to do again   of course because uh because of the age that we  currently live in hopefully that won't be too long   and policymakers need to know about this stuff  because this is a huge economic problem quite   apart from the moral and social case uh to do  something about aging so i just thought i'd finish   uh in case you're interested with a few links uh  you can get uh if you're interested in getting a   copy of the book you can go to asia.link i know  you can also buy it from the commonwealth club   bookshops that's not a good place to look as well  and here are just a few different places you can   find out a bit more about me uh on social media  and that kind of stuff i'm at stato on twitter   i'm dr andrew steele on youtube and facebook uh  andrew j steele on instagram and i think that's   just about it so i think robbie's gonna come  back now and we've got time for a few questions   wow that's quite a journey andrew thank you so  much thank you i have i have a lot of questions   and of course i have some from the audience too  look let me start with my first question which   actually comes from the end of your book and  it relates perfectly to how you ended your talk   so there's a call to arms here and you say uh i  hope this book has convinced you that it's time   for a mission driven medical moonshot a massively  funded international program of research   to intervene in the aging process what would  that look like and how can we all help you   achieve that goal oh you've given away the ending  this is terrible no one's going to read it now   um yeah i think this is just a really really  important thing it's the reason i think the   primary way that we're going to do this is just  spreading the word about aging biology and that's   really why i wanted to write this book because i  think i think something that's very important that   people can do is start to write to politicians  and engage with policymakers you know just tell   anyone they know particularly those people because  the volume of post in their postbacks i think is   a real way that politicians gauge you know what's  hot and what's not what voters care about in the   world but also they're going to respond to sort  of broader uh demographics of voting you know   people understanding this thing and people knowing  it's a really really serious issue and just making   the case in a variety of varied ways because you  know i hope that i'm convincing speaking about   this but i know there are certain politicians who  just you know wouldn't be interested in this very   sort of dry statistical presentation you could  characterize it as that i've been trying to give   here you know perhaps a more folksy story about  you know particular old people or your particular   experiences in life is going to drive it home to  them it's just really important that we we talk   to as many people as possible in as many ways as  possible and i really think um a huge part of this   is going to have to be government funding there's  a huge and exciting space that i haven't really   talked about in terms of things like venture  capital in terms of you know private equity   starting to move into this field and there are  some really cool big investments as i said there   are like 20 or 30 companies working on analytics  there are a lot of companies you know too many   to count and sort of springing up every day trying  to do various interventions into the aging process   but what's really interesting is even though there  are so many sort of privately fundable you know   i think wise investors are going to make a pretty  penny off this you know form of investment because   the the potential market is enormous you know  it's every living human because we're all aging   nonetheless the investable opportunities are a  small subset of the total opportunity in this   field and quite a lot of it needs government or  philanthropic funding to bring it up to a point   where we can all you know get involved sorry where  we can get to the point where everyone can you   know we can think about investing and think about  springing this stuff out we're pharmaceutical   companies which always like to you know they  like to see the data they like to understand   what they're getting into before they do any sort  of speculative research and development so i think   a really really important thing is just to get  in touch with policy making you talk to your   representatives you know right to the president  however it is that you try and engage people i i   i'm encouraging people to write to their mps here  in the uk which is you know members of parliament   i think that's really critical and just telling  your friends telling doctors telling scientists   because everyone needs to know how important this  is and it's going to be an effort that you know   has many many different layers to it so so in that  quote that i i gave you talked about a moon shot   and of course the the uh the project to land on  the moon was was federally funded more or less   and uh and it was something where you know the  information the data the photos the technology   was in the public domain and so we've also had the  human genome project of course which was a three   billion dollar federally funded program and and  all the data was was put in the public domain so   so do you think that this big project that you're  describing is something that could be conceived   of in such a way that to use your terminology  it's for the benefit of the commons you know for   the benefit of the public rather than you know  fencing it off for all these private investor   corporate interests who want to own basically life  how do you think about that yeah i think there's a   huge part of this project which should be done in  this way and partly it's because only governments   have the money to sort of back this kind of  enormous and in some cases quite speculative   research because we've got multiple ideas for  each of the hallmarks of aging but you know   some of them just aren't going to come off i very  much hope so analytics work but the fact they've   worked in mice there's no guarantee that they're  going to work in people and so obviously the   things that are a bit further off you know that we  haven't already got a working proof of concept in   mice they're going to require further investment  further speculative speculative investment   and what's great about government is it can take  big speculative bets because the fact is there   so there are 10 hallmarks of aging and there  are 10 treatments for each the government can   bet on all 100 of those and it might be that only  five of them succeed but those five are going to   have such a massive return on investment you know  as taxpayers as corporations we're all going to   see a huge huge return on that whereas you know  if you're a private equity investor there's no   way that you're going to take on that enormous  portfolio knowing that 95 of them are going to   fail even if those five percent could more than  pay for it because you just how on earth you're   going to justify that to your investors so i  think that's really really important i think   another that you sort of raised the human genome  project i think that's actually a really important   analogy as well toward the end of the book i  talk about um the real importance that we've got   of of documenting some of the changes that  happen with aging so we've got these 10 hallmarks   it's probably not an exhaustive list because we  don't fully understand the biology it's definitely   enough to be getting on with you know there's  lots of research that could be done but what's   really surprising is is how how non-quantified  this work is so for example there's this sudden   buzz around senescence cells and analytics  now because of these fantastic early results   but we still don't really know which organs  for example in your body accumulate the most   senescent cells what percentage of the cells in  your liver at age 75 are senescent i don't think   anyone really knows the answer to that and it's  kind of surprising because that's going to to some   extent inform therapy as i as i sort of suggest in  the talk the first therapies are going to be for   specific places where we know that senescent cells  drive a particular disease rather than just you   know clearing out senescent cells and aged bodies  but it might be that you know senescent cells in   your liver are particularly numerous or for some  reason a particularly strong driver of the chronic   inflammation i talked about i'm making all this  up by the way there's no there's no real evidence   to suggest any of this but the fact is that we  don't know the answer to these questions we don't   know whether essence cells are we don't know how  many of them there are and knowing that answer is   going to be a huge prerequisite to making sure  the treatments can work so i think there's a   there's a huge sort of treasure trove of data that  again only government is really in a position to   unleash and then of course there's going to come  a point where pharmaceutical companies and private   industry and investors have to get involved  because rolling this stuff out is something   the private sector does really really well but i  think it's really important that we both invest   heavily publicly and think ahead to make sure that  we you know ensure equality of access and ensure   these drugs aren't you know sold at ridiculously  high prices by pharma companies and so on there's   a huge amount to talk about and debate here i  think we just really need to get stuck in as fast   as possible so maybe a publicly funded project  on a large global scale that was investable   in certain ways by the private sector i  think so and i think that's the you know   the way things work at the moment isn't perfect in  any sense but the fact that you know universities   can get to a point for example where you know they  developed a project to a sufficient stage where   it's got enough you know enough preclinical data  that a pharmaceutical company might be interested   in taking it on i think there's nothing like  intrinsically wrong with that model wrinkles   and flaws though there are in it because you know  it means the public sector can you know bear a lot   of the risk in the early stage research and then  hopefully you know we can you know we can we can   spin these things out the point when they are  commercializable when it's you know when it's   clear or hopefully clear there's something  to be had there so i'd like you to clarify a   point for me when you were talking about  the hallmarks of aging i made a note here   which it struck me that that you you're largely  talking about individuals it seems to me so it   seems to me that that an individual ages and dies  because an individual is mortal but that a species   uh in a way is eternal i mean unless  there's some catastrophic environmental   situation that so can you say something  about how you know evolution has has created   a situation where once an individual has  reproduced and raised the next generation   or perhaps you know the grandchildren they are  less useful than say another younger person who   can reproduce if you think of it at the level of  community or tribe or or species uh isn't aging   just a natural process that we should accept yeah  i think the way you've posed that i'd actually end   up going the other way so you know you're talking  about the idea of the species and society there's   all these sort of ideas that are bigger than the  individual i think a lot of modern evolutionary   biology thinks about things not on this grand you  know social or you know even global scale but on   the level of individual genes and that's because  the genes are the things that are eternal or the   things that have the potential to be eternal  because they can be passed down from generation   to generation and a gene that in combination  with the other genes in your body makes you more   likely to survive and more likely to reproduce  is one that's going to carry on in the gene   pool and i think um the best way i've come up  with to think about the evolution of aging is   we talk about evolution as survival of the fittest  the best way to really think about evolution is   reproduction of the fittest is those that are able  to reproduce the best will by definition pass on   their genes more readily to the next generation  and those next generation will then be better   able to reproduce because they've got those  favorable genes and they'll carry on expanding   into the population and evolution will trade off  literally anything to improve your reproductive   chances it doesn't care it doesn't care if you've  got you know long legs or short legs big muscles   or small muscles you know grey grey fur or brown  fur it will do whatever it takes to increase your   possibility as an organism of reproductive success  by you know effectively by meddling with your   genes if we think about evolution in a slightly  anthropomorphic way here and lifespan is just   no different so there are contexts if you imagine  you're a mouse you're a very small organism you've   got a lot of natural threats you can get eaten  by a cat you can get a disease mice are so small   they often digest of exposure because they get so  cold in the winter that they just freeze to death   basically and so they've got a very short natural  lifespan even if they didn't age at all and so   evolution can either invest a load of energy in  making them you know cancer-proof bulletproof   ageless organisms or it can put a lot of energy  into making them reproduce really really quickly   you know fire out those kids and then effectively  they're gonna die of something else before they   have a chance to get old whereas if you look in  a different context there are some animals like   giant tortoises or like human beings actually you  know a giant tortoise has a big protective shell   it means it hasn't got serious natural threats  on the islands on which they've evolved if you   look at humans one of the reasons that we're  so long-lived is actually because we're social   because we can club together we can share  resources we can share knowledge it means that   we're much less risk of things like predators than  than we would be if we were you know less less   intelligent animals and so evolution there decides  to trade off and say actually you can reproduce it   more slowly you can live a little bit longer and  even in some cases like as i said in the tortoises   or in the hydra evolution has gone well actually  the optimal way to maximize your reproductive   capacity is to give you a risk of death that  doesn't change with time there's a fantastic   paper i'm afraid i've completely forgotten the  reference for it but it shows all the different   life courses so all the different graphs of risk  of death for time basically uh across a whole   range of different creatures and they are all over  the place some of them have a lump and then go   down and come up again some of them are you know  flat some of them shoot up like human beings do   some of them actually go down with time there  are organisms that have negative senescence   evolution is stranger than we can possibly  imagine it and it will trade off literally   anything including how long we live  to make us reproduce more frequently   so i have one question from the audience and then  i'm going to ask you for a final remarks okay   so this is a little outside your talk but it  is related so the question is what's your view   on on exercise vegan diet meditation and positive  thinking together working as well as uh analytics   i mean we know we all believe that doing the  the quote-unquote right thing in terms of   eating and exercise is good but is there science  behind that too there definitely is and actually   i think one of the most compelling studies that  i found is a chapter of health advice in the book   and um the the reason there's that chapter  actually is a variety of different things firstly   because i think understanding the underlying aging  biology makes me a lot more excited about what   you know sounds like quite quite basic health  advice because you find things like exercising   enough things like eating the right food things  like not smoking please do not smoke that's the   single most important thing i can convey to anyone  you know listening to this um they literally slow   down the aging process and understanding that  biology you know makes them a lot more compelling   even though they might not necessarily sound that  fascinating i think um yeah it's absolutely right   to highlight these things are important another  really compelling study that i found showed that   um by by doing i think there are five different  healthy lifestyle behaviors and it must have been   not smoking eating well not being overweight  getting enough exercise and i can't what the   fifth one was now but something like that they  did a study in nurses and they they might have   been sleeping well you're absolutely right i  could that could have been it they found these   people lived five or ten years longer if they take  four of those five boxes compared to if they take   none of the five boxes so there's clearly a lot to  play for and actually i think your the question is   exactly right it probably will be comparable in  effect to the first generation of analytics i'm   sure we can do better than that once we start  to you know optimize these therapies but i'd be   really shocked if you know the first generation of  analytics knocks exercise out of the park there's   this joke that doctors have that if exercise were  a drug everyone would be queuing up to take it   because it's effects they're just so wide-ranging  and positive but the second reason i really um   really wanted to include that health  span the health advice chapter sorry   is because i'm really excited about this because  the longer that we can all live in good health   the longer we give scientists to develop these  treatments the more chance you are you have to   be alive and the first generation of analytics  or the first gene therapy or the first stem   cell therapy that can sort out aging is you know  brought into production and that just means that   you know your potential lifespan could be vastly  vastly longer than you're guessing now because if   you can be healthy enough to take those treatments  at the time when they're rolled out then you know   that could add you know more years to your  life giving scientists more time to develop   more treatments and so on so i just think you know  the health advice stuff some of it can sound quite   boring there are some other bits that are a bit  less conventional i talk about in the book but   you know it's so so important just because it does  have a big effect and that effect could be an even   bigger effect amplified by all the progress in  asian biology well thank you andrew we're at the   end of our program so one of our i so cardinal  features of the commonwealth programs is we like   to leave our audience with either something  to do or something to think about so here's a   chance you to give us kind of a final remark that  you want us to leave this program thinking about   i think the thing that i always tell people and i  i mean i've already said this to some extent but   the weirdest bit of health advice i give out is  to write to your representatives write to your   senators write to the president tell them about  the importance of aging biology and that sounds   weird but i think the single biggest determinant  of how long most people alive today are going to   live is progress in aging biology and so the more  that we can do to spread the word um you know the   more you know please read my book obviously it  sounds a bit self-serving but that isn't intended   to be uh intended to be that way the more people  who understand how important and significant   this could be the greater our chances of living  longer and healthier lives and the greater the   chance of everyone you know and love and care  about living longer and healthier lives too so   i just think that's so so important and if you can  find the time to do that that would be fantastic   well thank you dr andrew steele i have to say  when i came across your book which i've read and   thoroughly enjoyed i thought i must meet this man  so i'm so grateful that you were able to travel   across the ether from the uk to talk to us  here today i'd like to thank our audience   for uh listening to this program and in about  10 days or so this will be available uh on the   commonwealth club website and so you can see  it again and you can share it with your friends www.commonwealthclub.org i encourage everybody  who's watching this program to become a member   contributing member for a mere five dollars a  month allows you to support this this type of   programming so um what else do i have to say for  118 years the commonwealth club of california   has facilitated open dialogue and we look  at all issues across the spectrum of society   to produce a healthier society and hopefully  to live longer and a higher quality life   and of course dr andrew steele you've  given us insights into how to do that   so thank you again for your time buy the book read  the book and live longer thank you bye for now you

Channel: Commonwealth Club of California

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Length: 64min 43sec (3883 seconds)

Published: Tue Aug 03 2021