An Interview with João Pedro de Magalhães

João Pedro de Magalhães is one of a number of people from the small online transhumanist community of twenty years past who went on to focus on aging research. The present all too short human life span is the most pressing and harmful of limits upon the human condition, and the more people who seek to do something about that, the better. Like many of the more established researchers in the field, de Magalhães has come to think that radical life extension of decades or more in our lifetimes is unlikely, however. To my eyes that is only true if the SENS approach based on repair of root cause molecular damage fails to gather significantly greater support over the next two decades. There is a lot of room yet to achieve great things, especially now that the first SENS approaches are close to the clinic, such as senescent cell clearance.

What are you currently working on?

Although my work integrates different strategies, its focal point is developing and applying experimental and computational methods to help decipher the genome and how it regulates complex processes like ageing. In practice, that means developing and employing modern methods for genome sequencing and also bioinformatics to analyze large amounts of data, for example networks with hundreds of genes. We now know that aging and longevity, like many other biological processes, derive from many genes interacting with each other and with the environment. My lab develops methods to survey and analyze data from thousands of genes simultaneously to identify the most important ones. More specifically, we are now studying new genes associated with aging and longevity as well as new cancer and Alzheimer's disease genes. If we can identify which are the key genes modulating aging or age-related diseases than this will open new opportunities for developing therapeutics. We are also studying new life extending compounds using animal models.

What do you think is the most important contribution you've made to the field?

I am probably best known for the online collection of databases I created, the Human Ageing Genomic Resources (HAGR). I designed HAGR to help researchers study the genetics of human ageing using modern approaches such as functional genomics, network analyses, systems biology and evolutionary analyses. They have been cited hundreds of times and are used widely by the biogerontology research community, facilitating a lot of studies. I am also known for the work I did on sequencing genomes of long-lived species, in particular the naked mole rat and bowhead whale. Lastly, my lab developed various computational approaches to analyze large amounts of data as well as predict new genes, processes and drugs associated with aging and longevity.

What is the approach to fighting ageing you find most promising, besides the one you're pursuing?

There is certainly a lot of promise in stem cells and regenerative medicine. So I am optimistic that there will be new advances and therapies, although things normally take a long time in clinical translation. I'm not sure that telomeres and telomerase will play much of a role. I think telomerase may be used in regenerative medicine and to treat specific diseases, but it is unlikely to become a source of anti-ageing therapies because it also promotes tumorigenesis. Besides, mice have lots of telomerase and yet they age much faster than us. It's some years old but I wrote a review on this topic where I expressed my skepticism of telomerase as a therapy for aging.

Do you expect to see the day ageing is finally defeated? What you will do after that?

I don't think we will defeat aging within my lifetime. I mean, we can't even defeat aging in simple animal models, or defeat a number of simpler human diseases (I have a nasty cold as I write this, like I have every year). So I don't think we will cure aging in the foreseeable future. Like many others in the life extension community, I think cryopreservation may be a plan B, even though it's not a very attractive one (but it's still better than dying!). That's why in the past few years I have become more involved in cryobiology and cryonics. While I am not convinced that the current techniques used in cryonics allow preservation of the self, I think the field can progress rapidly to the point of us as developing reversible human cryopreservation well before aging is defeated.

Link: http://www.leafscience.org/dr-joao-pedro-de-magalhaes-a-life-dedicated-to-conquering-ageing/

Comments

Just wondering why he doesn't think that we'll defeat aging in his lifetime since he's quite young. Could it be because his research focuses on genetic reprogramming?

It seems strange to me that with senescent cell clearing, immune system regeneration, transthyretin amyloid removal, various genetic tweaks (e.g. telomere elongation, myostatin inhibition), organ patches, as well as more effective immunotherapies for cancer on the near horizon, people who are willing to try out medical tourism won't be able to add a decade or even two to their life expectancy within ten years.

This would allow even someone who is currently 60 to push 100, thus giving early adopters approximately 40 years from now before they reach the biological equivalent of 85 - aka current life expectancy in some developed countries.

Even with funding at suboptimal level, if the momentum is not lost I find it difficult to believe that by the late 2050s we will still be struggling with cleaving glucosepane or moving around mitochondria.

Posted by: Barbara T. at April 13th, 2017 12:36 PM

I imagine it has something to do with his wife dying recently.

Posted by: Anonymoose at April 13th, 2017 1:53 PM

@Anonymoose perhaps though he said this long ago too in his senescence blog a number of years ago. He just does not think we can do it soon, though he hopes obviously we can.

Posted by: Steve Hill at April 13th, 2017 3:09 PM

Maybe it has to do with his approach to antiaging, basically tweaking metabolism to slow aging. I agree with him that with that approach we will not defeat aging in our lifetimes.

Here is his view on SENS: http://senescence.info/sens.html

Posted by: Antonio at April 13th, 2017 3:55 PM

In summary:

"Part of the problem is that SENS, like the proposals of futurist Ray Kurzweil, depends on technologies that have not been developed yet and thus may or may not pan out. The unpredictability of biological systems, in particular, is a key issue to render SENS very optimistic in my eyes. I personally think that a much deeper understanding of biology, and specifically of the machines of life, is essential to develop the level of sophistication in biomedical research (including pharmacology, synthetic biology and regenerative medicine) required for curing aging. Hence, the focus of my work is not on SENS but on increasing our knowledge of aging and on genomics"

Posted by: Antonio at April 13th, 2017 3:57 PM

I don't agree with his criticism. The technologies needed for SENS already exist or are being developed at a fast pace by the mainstream research community (iPSCs, gene therapy, tissue engineering, etc.). What is needed for SENS is only to apply them to the particular 7 damage categories.

It's like Mars colonization. We already have the technologies to do it. We only need to put the money, design the rockets, the spacecrafts, etc. and build them. No new technology is needed.

Posted by: Antonio at April 13th, 2017 4:08 PM

@Antonio: Thanks, it makes sense now. Still a bit miffed that he seems to be ignoring the technologies that were developed over the last couple of years, as well as plenty proofs of concept. His statement that telomerase causes cancer (or that there aren't techniques that could prevent it, such as intermittent and finite elongation) and that life hasn't been extended in small animal models sounds a bit anachronistic too.

Interesting how even anti-deathists sometimes get so bogged down in their line of research that they end up discarding signs of real progress in neighbouring approaches.

Posted by: Barbara T. at April 13th, 2017 4:14 PM

Barbara T.: Yeah. Also his comments about cryonics seem oudated. It has been already shown that cryopreserved C. elegans retain past memories after revival.

Posted by: Antonio at April 13th, 2017 4:55 PM

I also find it strange that the more progress is achieved, the more established scientists like de Magalhães and Mitteldorf seem to lose the belief that radical life extension is within reach. It could be that theories of programmed aging - with the inherent complications that they bring - are gaining a serious foothold even amongst engineering-minded transhumanists.

Still, even if it turned out that the the application of all seven SENS therapies increased life expectancy to "only" the current maximum of 115-120 before epigenetic mutations other than cancer started killing us, that would still buy a hell of a lot of time even to people currently in middle age. Therefore even these people (let alone someone in his early 40s like de Magalhães) may very well have a shot at benefiting from therapies that will be available 5 or 6 decades from now.

Posted by: Barbara T. at April 13th, 2017 5:07 PM

AFAIK, Mitteldorf has always been in the programmed aging camp. But anyway I don't know him very well, so maybe it was different some years ago.

Posted by: Antonio at April 13th, 2017 6:59 PM

Hi all, Just my 2 cent,

I think that the reason why these biogerontologists lose belief/hope that life extension is going to happen (anytime soon) is because of the old saying : ''The more it changes the more it's the same''.

These biogerontologists would hope that indeed life extension is possible (and I am of the opinion it is) but with so much failure in the past - how could anyone do it... they believe in the possibility but that possibility is microscopic. As such, when we hear about another 'baby step' forward, of course it's truly great thing; but there is World of difference between removing senescent cells - and immortality. Or saying that 7 damages = cure death.
I'm not saying it's impossible (it is Very possible) it's just they are unimpressed (I feel them) because it takes More than that (to impress them or make them reduced their pessimism - which a very Founded pessimism, not out of thin air - there is rampant pessimism because on face-value it looks like BS - but it Not BS - because AdG has very specific(ally) ways about going about it - but we all know them and they are nothing 'to write home about'; AdG is
very confident and that's a good thing; it could be his confidence in his work and SENS that could change the world (albeit, there I have a slight pessism because I spoke at great length why previoulsy (in short, none of the 6 therapies will stop certain problems of aging; only one might have a chance, the 7th. Although, AdG or somebody else may add new therapies we don't know yet (although there too I'm not so sure, because it really is SENS doing most of all of the 'life extension' endaeavoring and pushing - the rest do jacksquat but 'study and study and study' some more - because we don't understand Enough Aging...chr*st I think we know Quite a lot but some want to Know So Much More...it Never Ends. If we keep on styding aging - we could be here till in 500 years and still 'studying 'for studying' (that's the same sh...as
doing lots of 'talking' and no 'walking' (the talk); or like a writer Talking about 'writing (something)'...and never 'writing' anything..

I think at a certain point you
need to Something about it 'to act on it' not keep studying for studying (some more) But scientists think we know sh...so 'study' some more. I think SENS is doing the good think 'Of Acting on their Theories/Hypotheses/Hypothetic Studies/Conjectures' - took the lead
(no matter others see it as a 'bad joke'/scifi-bs more than anything or even snakeoil/seeling a pie in the sky/pretty words/empty promises). That said, we do see certain advancements
(like senescence clearance etc...also he's wrong about the cancer thing - if cutting cancer's telomerase/or reducing telomeres even further/blocking ALT..does not really work there is also magnetic-field controled nanobacterias (as bs as it sounds it's true) that target hypoxic regions of tumors to deliver cancer-destroying agents (do a job as good a nanorobots, so now we 'have' nanorobots in the form of magneti-field controled nanobacterias. Of course,
this is still very new tech but it'S going to improve and soon nanobacterias will be used not only cancer cell clearance, but also senescent cell clearance, junk clearance any crap inside will be 'dusted off' by these nanothings).
With that said, right now as it is, the combined therapies would allow someone to live longer and healthier; it's assured for it targets the critical elements responsable for (mostly) pathological aging (which may or may not display accelerated aging) - not so for regular intrisic aging which relies on different pathways (such as replicative senescence, chromosome decondensation, epigenetic drifting, redox loss, ETC ROS-mitochondrial lipoperoxidation causing IMM degradation, etc). Pathological aging relies on Nearly the same pathways but in regular 'long' healthy aging all of this is 'slowed down' - but it's still continuing it's course (as such you die one day (of much deterioration due to the regular aging mechanisms caused by Oxygeneation Respiration/Rusting ROS mitochondrial emission/
age pigment accumulation (lipofuscin among others), loss of redox function (NAD/NADH couple lost, redox catastrophe) - despite being healthy all the time). I think that's why these biogerontologists are sceptical (if, too, hope that aging would be cured), it's because
there is no easy way to get there and when someone says so - their 'defense mechanism go up/b*llshit spidey senses tingling''.

I think most biogeront. feel that SENS will be Helpful and allow, possibly, a much longer lifespan in health - and even, possibly reaching 110-115 - maybe 120... on SENS - Despite Combining Them All Together. But that's it (mostly), there is no real True life extension
- in terms of maximum human specie lifespan on SENS (Except lysosomal therapy that could maybe make us reach 150 and over; because of age pigment control (proteasomal maintenance),
and as such, redox thiol control). But there will be a Middle/Average/Median life extension or Life Expectancy increase by SENS (improvement in Health and Avg.lifespan/Healthspan; Health should be the first element that improves, lifespan will increase a bit
by better maintenance of health - but that is not 100% sure - sudden death happens even in rather good health, like a specific dysfunction in a single organ (organs don't age all at the same speed and are co-depedent and co-Interdependent. That's why you can see a child
have cancer or a woman of 22 years old have near-full head of grey hair (like my grand-mother had, she 'turned grey' in her 20s... yet she lived to 92 years old....try to explain that. It's inherited genetics. Certain specific parts of our body may go much faster than the others, they age roughly at the same speed - or can age even faster or slower/get more mutations than the others).

Perhaps a 20-30 years will be added, I doubt it will add much more (like 40 or over) because in the past every single kind of life extension therapy as failed (miserably) - ok they were obviously not SENS, we knnow that much but we cannot discredit them - many of these former tries were based on mechanistic pathways that Reach/intertwine those that SENS targets.
I mean the body is one huge interconnected 'web/network', so of course, wherever you 'Get In' you end up to the same place because every pathway is (inter)connected/(inter)linked somehow - so obviously, the past tries Surely Touched a Target that SENS aims to target. In 50 years, it might be quite different - but not that different altogether, that's the point of Mr.de Magalhaes - baby steps - we spents Billions on cancer - no cure - yet .. somehow we can cure death before with SENS (I'm just stating how it sounds to 'biogerontologists', they think it's a joke, unfunny joke -since they are the ones who Tried Hard to make life extension or even just curing CAncer - so it feels like a slap in the face or a misplaced joke when someone says : 'hey I got this figured - 1+1 = 3...uh... I mean 2).
Just my 2 cent.

Posted by: CANanonymity at April 13th, 2017 8:02 PM

I meant that people who were optimistic, a few years ago, about radical life extension being within reach are now much more skeptical... even though the greatest breakthroughs - at least in terms of proof of concept - occurred after 2010. As Mitteldorf says: "Prospects are good for real breakthroughs, perhaps as soon as 2017, but I am no longer as optimistic as I was just a few years ago that complete rejuvenation is on the horizon". I just wonder what is causing this swing in the face of increasingly fast progress.

Posted by: Barbara T. at April 13th, 2017 8:46 PM

@Barbara T.

Hi Barbara, Thanks for that !

just 2 cent, it's Maany things..
I think it's the whole roller coaster thing and 'fad thing/'anti-aging in fashion for a while'), one minute you hear 'good news' the next your hear bad news (kind of like when scientists said :''Ok don't smoke, it' bad''..and then the next minute or so ''Ok, smoke, it'S actually good - centenarians smoke their while life, like Jeanne Calment smoked from 20 to a 100 - so do it - it,s *Very good*, these tar carcinogen chemicals will make you live 150''....

Who do you trust, who do you believe ? There is lots of confusion, contradiction and study upon study that refutes or agrees to past study (and many studies' results did not end up increasing lifespan - it's failure after failure/deception 'Allllmost There - But Not Quite' That little thing that we lack). And so new results come in an discredit the past ones...but You Thought All Along the Former results were Supposedly the Saint-Truth... and abided by them what deception

Bam...another 'News' comes in and your world/beliefs are shattered..you were 'in the wrong' all along - Thanks to these 'former' studies making 'claims' that were altogether false. All FAlse.

That.

It breaks your confidence/Believing/trust/Hope in the whole thing.
Not just that, it's the Tangibility thing, SENS has nothing tangible (Truly) except SENS cell clearance which is at least Something; but to people (regular ones on the street who are the intended targeted audience full of diseases and that don't live long because of said diseases),
it sounds 'bitter-sweet' huff and puff/Fluff, 'airy' talk...thin air. You can slap so many 'studies' in their face...they need Tangible - they need Human that is cured to Believe it with their own 2 eyes. Otherwise, they have -veerrryy- engrained opinion about it; mostly a fatalist opinion (it's useless, don't eve try, we'ere dead anyways, 'we age/learn to 'live with it' while you'Re still alive (and soon dead) so Accept Death...don't be scared/earth will be overpopulated/Costs So much for therapy/blablabal..on and on with ethical stuff).

Once we see Some Therapy it will Truly Get the Ball Rolling and Change quite a few people's opionions to say 'Hey ... It... Could... Be.... Possible...I could live longer Healthier..who would of thunk It - Surely Not Me (SENS is BS..I was Wrong..SENS is not BS, there is some truth there - we might be able to live longer so I will give it a shot)'.

This will only happen if is tangible : Available to the public, not a rich privilege thing( though at first it will most likely be), and not some 'medical tourism' (like Mrs.Parrish CEO Bioviva Telomarase god knows where in some South American (shady?) private clinic (don't get me wrong I am For privatization and not just government thing) because FDA, Health Canada, and Europe Health are not helping with so much regulations (they want our Best it's understood, but with so much body regulation it greatly hampers 'trials' and tests in humans...so it may never happen in the next 20..30 years (it took 9 years for 3 genes in mitochondrials allotopic expressions...there are 10 genes left...if you the math (if all things equal in terms of speed of progress (even if AdG said :'the first ones will be the 'hardest/longest' ones and then it will Accelerate for the last therapies...many said that...and look were we are/it doesn't always translte into acceleration as time goes/more like 'freezing' effect))

Then it will take 30 years for the next 10 genes (if it took 10eyars for 3 genes) - what bout the other 5 or so therapies - combine all of this and surely we have a total 50 years at the Very least for all 7 therapies)). That's obviously the more pessimistic side, but sadly, lately this pessimism as translated as more True than false (Realistic pessimism), in the de Maghalaes text he says AdG biogerontogist opponents said (which I read their texts gainst AdG and have validity/but AdG responded with clear responses that made sense, if slightly overoptimism in him) :
''Excessive Optimism'' (like a faery tale/faery tales do happen : humans going in space/on planet/building ships rockets/building airplanes and flying/seeing the internal world in microscopte..but these Feats are rare and take time to happen (almost always 25-75 (50 av.) years interval between each). I read old papers from 1930s, 1920s, even 1860-80s..it's fascinating, there were not that far more us - yet they were. They talked about stuff that is relevant today almost a cetury ago; why would cure it now or in a century (progress is accelerating yes, but progress can stagnate - for decades. We may be entering in a sort of stagnation - despite advancements (where those advancements 'are nice' but Still Not Enough; just like the advancements were a century ago, many ended-up dusted under the carpet rug and lie there (it seems we dustem them off to 'restudy' them...we may have to reput them under rug- Again). (PS: sorry my wads of typo/errors).

''2 'cent.

Posted by: CANanonymity at April 14th, 2017 1:54 PM

@CANanonymity,

"Then it will take 30 years for the next 10 genes (if it took 10eyars for 3 genes) - what bout the other 5 or so therapies - combine all of this and surely we have a total 50 years at the Very least for all 7 therapies))".

Discoveries in 7 different fields are not consecutive but to varying degrees parallel, so it could take 10 years or 100 to have a comprehensive suite of SENS therapies. But this may not even matter...

For example, it could take 100 years to cure cancer with ALT, but in terms of making mortality rates low enough to enable the addition of 30-40 years to current median life expectancy (provided that all other wear-and-tear issues are taken care of) ALT may not be necessary, since incidence can be reduced through other means (e.g. senescent cell clearing) and immunotherapies may end up controlling a large portion of currently terminal cancers.

At the end of the day, you don't have to cure everyone of every disease for median life expectancy to reach 120 - only half the population.

So I imagine that the growing skepticism amongst once optimistic scientists is due to the realisation of what a mammoth venture curing aging via genetic reprogramming would be. What I don't get is why they don't believe that SENS or other repair-based approaches may allow a 40 year old (it will be almost the 22nd century by the time they are 120!) to live until technology is advanced enough to perform the trillions of operations needed to reprogramme humans genetically.

SENS may very well be 'just' a stopgap measure, but hopefully one good enough to get a lot of people currently alive to the point where epigenetic reprogramming is a reality - and this assuming that repair therapies will not generate a feedback loop able to trick the body into fixing itself.

My questions are: 1. Do scientists become so territorial / engrossed in their particular line of work that they end up acquiring a curious tunnel vision? If not: 2. What NEW evidence do they have to discredit the likelihood that within the next 20-40 years we will have therapies able to extend median lifespan by 40 years?

It would be interesting to hear their views.

Posted by: Barbara T. at April 15th, 2017 7:57 AM

barbara,

Maybe the scientists know something we dont? They are the ones doing the research after all. They know whats going on. If they are skeptical then maybe curing aging and extending our lives is very far off. No one has done this in a mouse yet let alone a human. Maybe we were born too early.

How old are you by the way?

Posted by: FuturePerson at April 15th, 2017 1:36 PM

Rehello, Very good points your bring ! I will try to answer the questions you emitted.

''...(provided that all other wear-and-tear issues are taken care of')''

I think that's where we may have difficulty in making it happen, the weat-and-tear that SENS will reduce will definately improve health - for sure because it targets important pathways that do this wear-and-tear that is consequential in pathological aging (like spontaneous or not-so-spontaneous arrivals of diseases); but this wear-and-tear will most likely minimal on
Regular intrinsic aging (the one we Truly want to cure = curing death ('of regular old age')).
Curing the diseases is of course more important first (because with them, it is assured we'll never reach of lifespan, that's understood; but it shouldn't stop there; the SENS therapies allow an imporvement of median lifespan by improved health and as you say reduced incidence mortality - allowing people to reach 120 possibly 'to be just in time for 'future' therapies that could allow LEV (Longevity Escape Velocity)). I do hope that but as it SENS probablly will not make LEV (except one therapy called LysoSENS that could (although I highly doubt it, alone it would it would need to be combined- but it carry that most massive effect because it would unclog our junkdisposal system which accumulate a Very Particular junk (lipofusucin) that is Causal to the Intrinsic aging (which is the one about curing death 'of old age'), the other junks contribute to mostly diseases but have much less say on Regular INtrinsic Aging like people who age 'healthily' and die at 110...why should they die then if they are so healthy why don't they live to 500 years...because intrinsic aging is limited by this particular mechanism of proteasomeclogging which in turn creates a cell that is full of junk and incapable of cycling/or repairing itself/keeping its anit-oxidative stress mechanisms intact which are crucial to preserve genome/chromosomal/mitochondrial integrity), but SENS as it is will definitely make increase median lifespan.

''So I imagine that the growing skepticism amongst once optimistic scientists is due to the realisation of what a mammoth venture curing aging via genetic reprogramming would be''

Exactly put.

''why they don't believe that SENS or other repair-based approaches may allow a 40 year old (it will be almost the 22nd century by the time they are 120!) to live until technology is advanced enough to perform the trillions of operations needed to reprogramme humans genetically''

Although there is advancement in the epigenetic reprogramming field and iPSC reprogramming it's sadly still very limited, like they use Stem cell markers to reprogramm (which is dangerous because cancer cells use Stem cell markers for hyperproliferation like Sox, Nanog, Oct, and so on. These special genes activate a plethora of other genes that 'rejuvenate' the cell to nearly a state of total reversal (as seen in iPSCs) but that's exactly what cancer cells also do and use). PLus epigenetic programming is about DNA methylation tinkering - it has not been great sadly - it shown that epigenetic drifting can be reversed but I was greatly saddened to see that epigenetic reprogramming it's not all it's up to be (like they did DNA methylation reprogramming in mice and obtained an increase in lifesapn of 30 or so % which is impressive, but why could they not reverse Aging altogether - that means that damages are more important or have a stronger say than we though and have more impact that global DNA methylation levels (not to say they are not important; just not - As - important as previously thought). Irreversible damage litteraly change the DNA methylation course and it's mostly irreversible, that's the main outcome it seems. But there are different types of damages, many are more important for pathological aging, while some few ones matter far more greatly to intrinsic aging (which is the one that I'm far more curious about; because that'S the only way we will beat the 150 mark and live those centurieS we hope, not 1 century and, Lights Out, that's it that's all)).

So that gets us back 'to damages' (yet) again. AdG rusting car analogy is very true, we need to know which part of the car matters more so that the car could actually 'make it' despite not having any doors, no tires, nothing left...besides the engine, tranmission and the body frame (which matter much more for 'how long that car will go on before it goes kaput').

So it's not to say 'to not hold on to reprogramming saving us'...but just don'T be Too opmistic about it because right now it's way too hard and not giving what we hoped. You know:
''Just Reprogram the DNA and methyl levels : Bang. Solved''. Nope.

But it will improve for sure...and it Could one day replace damage tinkering or always be used in combination repair + reprogrammation; it wouldn't surprise anyone ( of course) since the more therapies/tools in our hands the better we can fix aging - not just fix aging -
cure death once and for all.

''SENS may very well be 'just' a stopgap measure, but hopefully one good enough to get a lot of people currently alive to the point where epigenetic reprogramming is a reality ''

Very true, I guess we just have 'to hold on' in the mean time, not much else to do; it sucks waiting and 'guessing' and 'hoping' (it doesn't fail)...but it's always been like that.
Fingers crossed.

''- and this assuming that repair therapies will not generate a feedback loop able to trick the body into fixing itself. ''

The thing is the body is Already fixing itself (DNA repair/by thousand of enzymes repair, etc),
b but it falters; if SENS could make it not falter it would incredible; it would mean constant maintenance = immortality. Right now, it is not constant and becomes sluggish in futile 'compensation' attempt (to overrepair the accumulating damage/like self-over-exhausting) until it dies 'on itself'. It's akin to 'dying by a thousand needles stings.. ultra slow death'. Each micro-sting contributes to the near-linear downhill demise.

''Do scientists become so territorial / engrossed in their particular line of work that they end up acquiring a curious tunnel vision?''

That's quite true too, when you work a very long time in your field; and when someone (or some unknown nobody shows up at your door step to tell you how life works) you can have a very tunnel vision /stick to Your vision and not exactly like what 'new-in-town' new kid on the block person has to say. That's how biogerontologist feel, they feel they know their sh...(pardon the language), and when another one dispustes that - it casts a shadow on them and makes them look like clowns (suddenly - they are not Right... they Think they are Right...but someone else (like AdG) shows them : ''Hey...nope.''). Adg is probably the most incredible biogerontologist and (self-taught too) because he understood the whole thing. With that said, so do these biogerontologists - but as you their tunnel vision may block them from 'being more open' to these therapies simply because of Un-credibility/Non-credibility of them.

They don't think it's 'credible' or 'holds'.

''What NEW evidence do they have to discredit the likelihood that within the next 20-40 years we will have therapies able to extend median lifespan by 40 years?''

Like for example the recent study I spoke about that DNA methylation improved lifespan of 30% in mice by partial reprogramming (to avoid cancer formation from DNA methylation deregulation) but what happens in mice does not translate 1:1 in humans, that is more pessimism and loss of hope - had this mice live a 100% longer everyone would be up the roof...but no, it's about the same results you get with (CR) Calorie Restriction (meaning DNA methylation - Reaches pathways, the sames ones as CR). Are we excited about CR results - who do very little when done in Rhesus macaques monkeys and long-lived animal (they improve their health and reduce mortaliy/incidence..but on the sunject of lifespan it's rather inefficient or lackluster (I mean CR only in Long-lived animals not in mice. That means that DNA methylation tinkering in humans will be about the same 'rough' effect (since the same pathways))..just saying. My take is that DNA reprogramming - just like Stem cell injection did in mice (also a 30% or so lifespan extension by continuous stem cell injections for whole life) - will increase the average lifespan by improved healthspan. But will not cure death or make us live 150 alone (perhaps combined with SENS, but that starts to make an awful lot of therapies). I guess there is still New evidence that sorts of 'muddies' the whole thing and it's why it's always 'baby steps' and though it's one step at a time; it's still baby steps or failure/or stagnation - thus loss of hope altogether. Time goes and we are still not about to cure aging, that's why the pessimistic 'hold' still lingers and 'holds' on the biogeront.

They talk about the DNA reprogramming study :

1. https://singularityhub.com/2017/01/13/cellular-reprogramming-rejuvenates-old-mice-and-boosts-lifespans-30/

The link to the study's research paper :

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming
2. http://www.cell.com/cell/fulltext/S0092-8674(16)31664-6

Posted by: CANanonymity at April 15th, 2017 2:01 PM

PS: •Partial reprogramming erases cellular markers of aging in mouse and human cells
•Induction of OSKM in ***progeria mice*** ameliorates signs of aging and extends lifespan
•In vivo reprogramming improves regeneration in ***12-month-old wild-type*** mice

SO on top of that these not even 'Regular aging mice', these 'progeroid' (accelerated-aging) mice. So that more 'muddies' and 'discredits' the study and reprogrammation. In vivo reprogramming in 12-month-old Wild Type (Regular ones) improved regeneration - no 30% lifespan extension.....in the normal ones (that tells you that 'partial' (to avoid tumor formation) stem cell and epigenetic DNA gene reprogramming is a mostly 'health' improvement in both progeroid and normal mice. Progeroid mice living longer simply by improved health - thus, equalling to life of a 'regular wild-type' mice that does not suffer of accelerated aging (progeria).

Posted by: CANanonymity at April 15th, 2017 2:22 PM

@Barbara - I think you'd have to get a somewhat effective therapy in place for all 7 areas outlined by SENS. All of them wind up killing you at about the same time, probably because evolution pushed repair mechanisms or redundancy for each damage class to the point where aging of humans was not materially affecting their chance of getting their genes into the next generation.

In each of those areas there is disagreement amongst scientists about prospects. Ask researchers about cancer and Alzheimers and some think these will be to a large degree under control in 25 years, whereas others are much more pessimistic.

Posted by: Jim at April 17th, 2017 3:09 AM

I agree... but we we don't need to cure everyone of everything, just 50% of the population. I think that the big unknown here is cancer, since once you've figured out how to replace a pancreas or clear amyloid / tau or soften arteries, with repeated applications of the relevant therapy the effects should last a few decades.

The question is: how many of the people who are killed by cancer at the end of their current life expectancy would go on to get one (or more) bouts of the disease were they cured of it the first time around? The answer would allow us to calculate how much we would need to reduce cancer mortality by in order to get 50% of the population (provided that other known killers like senile amyloidosis etc. are taken care of accordingly) to reach any given X years of life expectancy. So, once 50% of senescent cells are destroyed, 50% of AGEs are removed and so on, how much do we need to reduce cancer mortality by in order to get 50% of the population to 100, 110, or 115?

To an extent, a model could be generated by looking at current incidence in different age groups, with the caveat, however, that we are unlikely to have samples of people - people who get cancer at 85, are cured of it, and then fall sick again with a new primary - that are large enough to allow for statistically significant results. Incidence in survivors may very well be different from incidence in previously unaffected individuals, and rates could be obscured by 90 year olds with potentially curable cancers being pressured into 'letting go with dignity' instead of syphoning resources away from more productive, younger members of society.

However, I think that we should either start producing more sophisticated statistical models than what is, to my knowledge, the only one that takes into account the elimination (in fact, x% reduction) of all diseases caused by the 7 SENS categories of aging, or stop making predictions altogether. Even the most cued-on scientists tend to be wrapped up in their own particular field of expertise and possess neither the knowledge nor the energy to build epidemiological models that take into account the hundreds of scenarios that could lead to a clinical if not - thanks to regulatory agencies - implementable 'solution' to aging within X, X+1, X+10 or X+n years.

For all we know, if the aim is to get 50% of the population to 120, the expected beneficial effects on cancer incidence of SENS therapies currently in the pipeline together with combination immunotherapies and CAR-T for solid tumours, could very well match the level of success that first generation ALT therapies are supposed to achieve.

My point is, we may not actually need all 7 SENS therapies to increase the life expectancy of a middle aged person to a point in time, say 2060 for argument's sake, that is so far away in the future that all bets are off. If by saying that we won't cure aging in our lifetime a 60 year old scientist means that we won't be able to turn a 90 year old into a 30 year old in 25 years time, I think that most of us would agree. However, a lot of adults alive today don't need this kind of 'cure' to have a respectable shot at living an indeterminately long life.

Posted by: Barbara T. at April 17th, 2017 8:06 PM

Barbara: Cancer mortality follows a Gompertz law, it doubles every eight years.

Posted by: Antonio at April 18th, 2017 2:17 AM

In summary, if deaths were mainly from cancer, 50% of males would reach age 110, but not 120. For females the exponential law is not so clear, so maybe 50% of them could reach age 120.

Posted by: Antonio at April 18th, 2017 3:48 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.