HN Books @HNBooksMonth

Not that hard to imagine and plan for:

http://www.ted.com/index.php/talks/view/id/39

http://video.google.com/videoplay?docid=8554766938711591377&...

http://www.amazon.com/dp/0312367066

http://citywire.kuluvalley.com/view/E586AD51-418F-C8CE-442B-...

http://michaelgr.com/2011/10/24/aubrey-de-grey-on-the-diseas...

⬐ ktizo

I didn't mean the getting old bit. Is just moving the foreseeable goalposts.

> Yet we are composed of trillions of cells, all 'programmed' to deteriorate over time.

That is incorrect. The diseases of aging are the result of evolutionary neglect, they aren't 'programmed in' as if there was a timer running. They're a bug, not a feature.

I suggest you have a look at:

http://www.amazon.com/dp/0312367066

http://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_ag...

http://www.youtube.com/watch?v=RbA1pFvfNp4&feature=gv...

http://michaelgr.com/2011/10/24/aubrey-de-grey-on-the-diseas...

The lack of progress so far certainly doesn't mean that we can't make progress, especially if we take a different approach and we use tools that weren't available before (and never underestimate using a different angle/mindset -- as long as we consider aging itself 'normal' and just something to be slightly delayed, we certainly won't make progress). The SENS 'engineering' approach mean that we don't have to understand metabolism or fix everything that goes wrong, just to periodically do repairs on whatever long-lived molecules are accumulating over time to cause pathologies. That's a lot easier than the past gerontological approaches of trying to understand and cure everything.

⬐ ChuckMcM

This is where I think we're headed. We're going to figure out exactly what all the moving bits do in our DNA and mitochondria and we'll be in a position to re-write it at will. When that happens, the question of what it means to be 'you' is going to get very pertinent, a safe example if it turns out your love of certain foods is a result of wiring in your brain due to your DNA makeup, do you change it? Do you add new foods? Do you delete old foods?

What happens to social justice when one person can afford gene therapy to make their children 99% more capable than average and others can't? If you ever saw the movie Gattica (not a great movie but it tried) don't worry about people who are born 'perfect' or born the 'natural' way, think about people who re-write their own genetics to have the mutation that gives Sherpa in the Himalayas more, and more efficient red blood cells. Very scary tech talk at Google on this once where a researcher in gene therapy was getting approached by trainers already.

⬐ maxerickson

I don't think I care at all if genetic modifications ruin athletic exhibitions (or the list of great mountain climbers or ...).

(I would say the potential for experimentation gone wrong is a much bigger concern;)

⬐ brador

Got a link to that tech talk?

⬐ ChuckMcM

I scanned through Youtube but it does not look like that one made it out of the Googleplex, sorry.

⬐ rosser

Pedantry: The title of the flick is GATTACA; it's a play on those being the four bases in DNA.

Quite agree with the rest of your comment, though.

⬐ lutusp

>> Yet we are composed of trillions of cells, all 'programmed' to deteriorate over time.

> That is incorrect. The diseases of aging are the result of evolutionary neglect, they aren't 'programmed in' as if there was a timer running.

No, the earlier poster is exactly right -- all living cells are programmed to deteriorate over time. There are no examples of immortal cells, with one exception -- cancer cells, like those that were harvested from Henrietta Lacks in 1951 and live on today in Petri dishes all over the world (so-called HeLa cells).

http://en.wikipedia.org/wiki/Henrietta_Lacks

http://en.wikipedia.org/wiki/Apoptosis

http://en.wikipedia.org/wiki/Programmed_cell_death

A quote from the second article: "Programmed cell-death (or PCD) is death of a cell in any form, mediated by an intracellular program.[1][2] PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. PCD serves fundamental functions during both plant and metazoa (multicellular animals) tissue development."

There is a reason we die -- it makes evolutionary sense. If there was an advantage to living longer, we would live longer. If there was an advantage to living a shorter time, we would live a shorter time. Our present lifetimes result from natural selection and evolution.

⬐ MikeCapone

You are looking at it the wrong way. Yes, from the point of view of an individual cell, you are correct. But from the point of view of a whole human, that's not how it works. At 25 pretty much all your cells have died and been replaced many times, and if over evolutionary times we had lived to be 500 years on average, we'd have mechanisms to keep up healthy that long. But we haven't, and so we don't, which is why everything starts going wrong as soon as you get to evolution's blind spot, past the age at which most of us lived and reproduced.

If damage didn't accumulate past thresholds that cause various pathologies, we'd basically stay young adults forever. If we can figure out how to fix that damage before it reaches those levels, that's what is going to happen. It's a lot easier to figure out how to fix those few kinds of damages than to change metabolism so that damage doesn't occur, or to cure diseases after they begin.

> There is a reason we die -- it makes evolutionary sense. If there was an advantage to living longer, we would live longer. If there was an advantage to living a shorter time, we would live a shorter time. Our present lifetimes result from natural selection and evolution.

What is "good enough" for our genes isn't always good for us as people. Most of what can be called "modern progress" is about protecting us from what would happen to us if nature was left to itself. Curing the diseases of aging is just the continuation of that (unless you don't wear glasses, don't live inside a building, don't wear shoes, don't get vaccinated, don't take antibiotics, don't wear any kind of protection, don't brush your teeth, would never have surgery, wouldn't get hearing aids, dentures, etc).

⬐ lutusp

> At 25 pretty much all your cells have died and been replaced many times, and if over evolutionary times we had lived to be 500 years on average, we'd have mechanisms to keep up healthy that long.

You're missing the point that some cells, essential to our survival, are never replaced, and when they decay, we die. One example is brain cells -- they're never replaced, and when they're done, so are we. This means that, unless we can get around apoptosis (programmed cell death), then we won't ever move beyond a certain age. We aren't close to understanding apoptosis.

> What is "good enough" for our genes isn't always good for us as people.

Ah, someone who thinks he can outwit nature. When we try to outwit nature, we end up outwitting ourselves.

> Most of what can be called "modern progress" is about protecting us from what would happen to us if nature was left to itself.

You mean, like antibiotics? The antibiotics that we have foolishly mismanaged to the extent that they simply don't work any more?

Contrary to your thesis, we need to figure out how to get along with nature, not pretend we can dominate nature. We've tried to run the show, and nature has responded by showing us how naive we are.

And this idea isn't some airy-fairy New Age philosophy, it's the result of careful scientific work. We're just getting started in figuring out how to get along with nature, and everything we've tried to date has backfired:

Medical and nutritional advances -> overpopulation

Antibiotics and other medical breakthroughs -> the gradual evolution of antibiotic-immune microbes.

Longevity extension -> overcrowding, a plague of chronic diseases in the elderly, deep philosophical questions about meaningless long lives.

> Curing the diseases of aging is just the continuation of that

Curing the "diseases of aging" is not your topic. Your topic is the disease of age. That's not the same thing at all.

⬐ MikeCapone

> You're missing the point that some cells, essential to our survival, are never replaced, and when they decay, we die. One example is brain cells -- they're never replaced, and when they're done, so are we. This means that, unless we can get around apoptosis (programmed cell death), then we won't ever move beyond a certain age. We aren't close to understanding apoptosis.

These cells can be replaced via stem cell therapy, and the more we look into things, the more we find that certain types of cells that we thought weren't replaced actually are.

> Ah, someone who thinks he can outwit nature. When we try to outwit nature, we end up outwitting ourselves.

That sounds really good, but I believe it's BS. You are anthropomorphizing nature. And every day you are "outwitting it" I'm sure. I bet you are quite happy for yourself and your loved ones not to be living like humans were living 20,000 years ago. And who's to say that technological and scientific progress isn't part of nature anyway? Why is curing diseases "against" nature? Not that nature is an entity in the first place.. All there is are the laws of physics.

> Curing the "diseases of aging" is not your topic. Your topic is the disease of age. That's not the same thing at all.

"age" is not an abstract thing that kills you. There are specific diseases of aging - which are diseases that old people get that young people do not get - that are curable, and that includes all the things that make us frail but aren't usually categorized as diseases (loss of muscle mass, change in texture of skin, etc).

Are you saying that Alzheimer's disease and heart disease and going blind and getting fat and arthritis and losing your muscles and sex drive are good things? If so, you are welcome to refuse these therapies when they are developed, but I will gladly take them, just like I'm sure you are taking advantage of all the other modern ways of making human life easier and more enjoyable.

You seem to be under what Aubrey de Grey calls the "pro-death trance"; happy that we cured smallpox and you wish we could cure AIDS and whatever, but you don't think we can cure the diseases of aging, so you find excuses for why they are actually good.

⬐ lutusp

>> You're missing the point that some cells, essential to our survival, are never replaced, and when they decay, we die.

> These cells can be replaced via stem cell therapy ...

Brain cells replaced by stem cell therapy? Have you given this any thought? A brain cell replaced by stem-cell therapy is empty -- it's not a replacement for the cells that contain the memory of your fifth birthday party, or that contain your knowledge of Calculus.

There's a reason brain cells aren't replaced -- it's the same reason you can't swap a running hard drive for a replacement that has no data written to it.

> "age" is not an abstract thing that kills you.

No, not abstract -- apoptosis is not abstract, it is a fact of life. And we have a very poor understanding of it.

> Are you saying that Alzheimer's disease and heart disease and going blinde and getting fat and losing your muscles and sex drive are good things?

Only you said that, and the remainder of your post relies on an argument only you have made.

> but you don't think we can cure the diseases of aging, so you find excuses for why they are actually good.

1. Stop making arguments for other people.

2. Learn the science. You have suggested stem cell therapy to replace brain cells, but without asking yourself what brain cells do, how they function. You would do well to learn that first.

⬐ MikeCapone

> Brain cells replaced by stem cell therapy? Have you given this any thought? A brain cell replaced by stem-cell therapy is empty -- it's not a replacement for the cells that contain the memory of your fifth birthday party, or that contain your knowledge of Calculus.

Maybe if you replaced all cells at once or something stupid like that, but that's not what is being suggested here.

http://en.wikipedia.org/wiki/Stem_cell_treatments#Brain_dama...

http://en.wikipedia.org/wiki/Neural_stem_cell

http://www.sciencedaily.com/releases/2012/04/120420105940.ht...

http://www.guardian.co.uk/science/2010/nov/16/stem-cells-inj...

From a quick search...

> No, not abstract -- apoptosis is not abstract, it is a fact of life. And we have a very poor understanding of it.

You have a poor understanding of it. First of all, a lot of the diseases of aging come about because apoptosis stops working and these malfunctioning zombie cells hang around and gum things up and produce erroneous signals/proteins. Rejuvenating the apoptosis process is part of the SENS platform. Cells that commit apoptosis are replaced all through your life.. It's when that process stops working well that things go wrong; they don't go wrong because of that process.

In other words, apoptosis doesn't make us old, it keeps us young. It's when it stops working well - along with other things - that we get frail and sick.

https://en.wikipedia.org/wiki/Strategies_for_Engineered_Negl...

> 1. Stop making arguments for other people.

I asked you questions, and you didn't answer them.

> 2. Learn the science. You have suggested stem cell therapy to replace brain cells, but without asking yourself what brain cells do, how they function. You would do well to learn that first.

Have you read Aubrey de Grey's book? It goes quite deep into the biology of his proposals (and he cites the papers that go even deeper). If you haven't, you don't even know what is being proposed so how can you know if it makes sense or not?

http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

I'm sure your public library also has it.

I highly recommend anyone who is interested in this subject read Aubrey de Grey's book on the current state of the science of biogerontology: http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

It's interesting, thorough, and optimistic. I also recommend donating money to SENS, as this cause is dramatically underfunded relative to its realistic potential to save and enhance human life for everyone. http://sens.org/

⬐ reasonattlm

Also strongly recommended: read the SENS Foundation 2011 annual and research reports, which outline for the layperson (while giving details for the scientist) exactly what biotechnologies the Foundation and its allies are working on, where present progress stands, and how mature versions of these technologies can be used to reverse aging.

http://sens.org/files/pdf/SENS_Foundation_Annual_Report_2011...

"We are delighted that SENS Foundation was able to make expenditures of $1,518,000 in 2011. This was an increase of over $400,000 from 2010, overwhelmingly in support of direct research and conference projects. ... We greatly appreciate the support of the many individuals who contributed to our mission. We would like to thank Peter Thiel, Jason Hope, the Methuselah Foundation, and all of our contributors and volunteers for their on-going generosity. We expect a significant increase in both revenues and expenses for 2012, as we begin to see distributions from a de Grey family trust, under a grant from SENSF-UK. This support will be in addition to the contributions we receive from other sources."

http://sens.org/files/pdf/2011_Research_Report.pdf

"The elasticity of the artery wall, the flexibility of the lens of the eye, and the high tensile strength of the ligaments are examples of tissues that rely on maintaining their proper structure. But chemical reactions with other molecules in the extracellular space occasionally result in a chemical bond (a so-called crosslink) between two nearby proteins that were previously free-moving, impairing their ability to slide across or along each other and thereby impairing function. It is the goal of this project to identify chemicals that can react with these crosslinks and break them without reacting with anything that we don't want to break.

"In 2011, we established a Center of Excellence for GlycoSENS and other rejuvenation research at Cambridge University and hired postdoctoral student Rhian Grainger to design and perform experiments to develop reagents that can detect proteins bearing glucosepane crosslinks, facilitating further studies on its structure, abundance, and cleavage by small molecules. We also established a collaboration with researchers at Yale University, who will lend their expertise in generating advanced glycation end-products and lead efforts in developing agents which may be able to cleave glucosepane."

It actually is inevitable, as even you admit when we begin to reach our 70s/80s ;). If we don't die of something else, all of us will die of Alzheimer's. Simple fact of universal amyloid plaque buildup. http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

Also technically incorrect on the mental decline as well - our brains do start to irrevocably decline at around age 30. Our myelin sheaths fully develop in the early 20s, and from there, we have a few golden years until it's all downhill :D http://www.sciencedaily.com/releases/2009/03/090320092111.ht...

We in fact know a very great deal about stopping aging. This book is a crash course in the science and what it means:

http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

If it wasn't illegal to commercially develop ways to treat aging, there would be a lot more progress than has happened to date.

http://www.fightaging.org/archives/2010/03/the-roadblock-tha...

Making humans immune to cancer in the SENS proposals is accomplished via this methodology:

http://www.fightaging.org/archives/2008/06/complicating-wilt...

But from where I stand, watching research fairly closely for some years, I'm not particularly worried about cancer - the next generation of targeted and immune therapies under development now will be highly effective, and are looking very good in the laboratory:

http://www.fightaging.org/archives/2010/01/the-prospect-of-c...

The $1 billion figure for realizing SENS is referenced in these items; I'm not aware of a full line item breakout:

http://www.sens.org/files/pdf/SIAAR-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf

We might or might not defeat the diseases of aging anytime soon, but if you want to help the people who are trying to make it happen, consider donating to the SENS Foundation (money goes directly to research):

http://www.sens.org/

Sadly, because aging isn't considered a disease by the FDA and other regulatory bodies, there is actually very little research being done on it if you take into consideration the fact that it kills more people than anything else in the rich countries (100-150k/day, usually after a long period of suffering).

If you want to learn more about what they are doing and why they think their engineering approach has a chance of success, check out Aubrey's book (the paperback version contains a new chapter, afaik):

http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

It contains a lot of biology, but should be understandable to the lay person.

And if all you want is a really quick intro, check out his TED talk (it's a bit old now (2005), but the general concepts have stayed mostly the same despite recent progress):

http://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_ag...

or the talk that he gave at Google (2007):

http://www.youtube.com/watch?v=wEyguiO4UW0

⬐ pohl

Thank you. I added them to my list at givv.org

⬐ None

None

⬐ MikeCapone

Could you please be specific in your criticism? Why would the engineering approach that he advocate not work? Why specifically is he a hack in your opinion?

Otherwise, it's just ad hominem.

⬐ abstractbill

Aubrey is a hack and about as far from being a scientist as I am from passing a Google technical interview.

Cambridge University awarded him a PhD for his work, and they don't exactly give those away on the back of cereal boxes. Do you have any hard evidence that he's not doing valid work?

⬐ jules

Before donating you should ask yourself whether Aubrey de Grey is a crackpot or not. I'm not sure myself. Can somebody shed some light on this?

⬐ JulianMorrison

He sounds like a crackpot when his theories are misrepresented. He's not saying "here's how I'll make you live to 1000". He's saying "If we solve this list of things, medical science will be able to give you on maybe another 30 healthy years of lifespan - and by doing this I can convince the world that ageing is so important, we will use those 30 years figuring out how to give you the next 30, and so on".

Edit: for what it's worth, the 1000 year figure is something that was calculated by estimating the chances of a person with the health characteristics of a young adult dying of any reason other than age - about 1 in 1000 per year, or an average of 1000 years life. That's just an average though - after early die-off of careless people, you might reasonably expect a 200-year-old to easily outlive 1000. And of course during that time technology won't have stood still - 1000 years ago, it was the dark ages.

⬐ philwelch

As it is, your expected lifespan is based largely on a finite clock, so any fatal risk factors are of limited value--if your odds of dying in a car crash are 1/1000/yr that barely affects your life expectancy, and if your odds of birth control failing are 1/100 you can go your entire fertile lifespan (30-40 years) without expecting to conceive.

If you get rid of aging (and other time-clock issues like menopause, though it would be stupid to get rid of menopause if people are going to be essentially immortal), life expectancy will be dictated almost entirely on these remote risks. Being more risk-averse might change your expected lifespan from 100 to 1000 to 10,000. And the less risk-averse people will die sooner, while the less risk-averse people (who are still unaging) will have free reign to change social norms in the long run.

This doesn't only apply to fatal risks. If you can work for 100 years at a day job and save up enough salary to live off the interest perpetually (and quite well), people are going to think it's crazy to do a startup. There's no sense of urgency when you don't age.

I think a world of immortal people would be very boring. And I haven't even gotten into the "slow-to-change" part (if someone living in the Middle Ages was still alive today, they'd probably be some kind of violent religious fanatic or something).

⬐ electromagnetic

Perfect use of the COCP lands your odd of getting pregnant at 0.3% in a year. However typical use lands you at about 8% (condom is 10-18% of typical use) risk, meaning you're doing good if you get a decade without getting pregnant (on average).

An indefinite lifespan will change the world ridiculously, however you're completely ignoring human nature. Those who take risks tend to be the ones who reproduce the most, and assuming fertility remains sustainable throughout life, those risk-averse will be quickly out bred. However, even considering the considered longevity of frozen sperm and embryos (women can still carry a child post-menopausal through egg donation - incidentally same odds as a younger woman).

You're considering risk aversion as the winner, when in reality it will be those who procreate frequently. If a couple produces 2 kids roughly every 20 years, that's 100 children they will produce meaning the risk averse will have to last 100,000 years just to match the genes of those who reproduce if their offspring never reproduce. Assuming a predisposition to reproducing at 20 (I've known all too many people with 4-generations of teenage mothers in their family, so it's certainly not an absurd prospect) and each two children produce two children in 20 years, you'd hit 1 peta-offspring by the 1000 year mark.

Your risk-averse would be marginally existent, similar to a dust mite next to an elephant. Their effect on society would be negligible to none existent. Compound interest has got nothing on exponential birthrates vs death rates.

⬐ philwelch

I think you're making a lot of big assumptions. First, the combination of indefinite lifespan, indefinite fertility, and high reproduction rates (which is necessary for your scenario) would cause rapid overpopulation. You have to give up at least one of those.

Second, there's no necessary reason fecundity should be related to risk aversity.

⬐ gte910h

He's looking for cures to issues that are real problems. If you fix any of the problems, even partially, they show great promise for helping older people to be decrepit, even if they don't actually extend lifespan. His hope is curing these types of damage will cause humans to functionally stop aging, but curing these types of damage are useful in and of themselves:

Cell loss, tissue atrophy

Nuclear [epi]mutations

Mutant mitochondria

Death-resistant cells

Tissue stiffening

Extracellular aggregates (Cleaning crap out of our bodies that shouldn't be there and isn't in cells)

Intracellular aggregates (Cleaning crap out of cells that shouldn't be there and is in cells)

⬐ DrJohnty

In some areas we are making rapid progress on some rather less but solutions are know to all 7 causes of aging as outlined below.

1. Cell death and atrophy: Treatable with exercise, stem cells, and chemicals which stimulate cell division.

2. Cancerous cells: Theoretically treatable with a type of gene therapy being developed, called Whole Body Interdiction of Lengthening of Telomeres (WILT).

3. Mutant mitochondria: Mutated DNA in the mitochondria causes a number of diseases. These can be prevented by moving the mitochondrial DNA into the cell nucleus, where the rest of the DNA resides.

4. Death Resistant Cells or Cell senescence (unwanted cells): Fat cells and other unwanted cruft can be removed surgically, or by stimulating the immune system to attack unwanted cells.

5. Tissue stiffening or Extracellular crosslinks (loss of elasticity): Certain proteins, such as those in cells making up the arteries, become too rigid over time because they bond to each other. These bonds can be broken with certain chemicals (some in clinical trials even today).

6 Extracellular aggregates or junk: “Plaque” which collects between cells can be eliminated by stimulating the immune system, and/or by using peptides called “beta-breakers.”

7. Intracellular aggregates or junk: Molecular garbage can be prevented from overwhelming certain cells by introducing enzymes which are known to be effective against such molecules.

In my opinion aging is no different to any other disease and like all diseases aging is ultimately treatable given the requisite technology. We cannot afford to sit back and simply accept that because everyone in history has lived and died we must follow the same path. It is a mistake to view aging as a fact of life set in stone when science has progressed to the level where we have the ability to begin the search for a cure. We might not be there yet but we are within striking distance of adding 20 or 30 years to our life expectancy and as Aubrey himself points out increases in life expectancy will be incremental and there is not going to be a sudden magic pill which you take and live forever. The essence of the engineering approach advocated by Aubrey is to manage aging, what he proposes is not a cure but a case of repairing the damage that occurs as we age at various intervals and not to stop the process but to allow the aging process to continue and repair the damage as it arises in the same way you maintain a house or car. This engineering approach is a case of taking advantage of improvements in technology as they occur and not to attempt to cure aging in its entirety and it is in this area that people fail to grasp what Aubrey de Grey is seeking to achieve. I recommend the two books below as great reading and all will be revealed!

Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime (Aubrey de Grey and Michael Rae) ISBN-10: 0312367066 ISBN-13: 978-0312367060

Transcend: Nine Steps to Living Well Forever (Ray Kurzweil and Terry Grossman MD) ISBN-10: 1605299561

I would also check out the following regarding Aubrey de Grey http://www.citywire.co.uk/personal/-/retirement/news-and-fea...

and also the following about Ray Kurzweil if this lot does not wet your appetite for joining the war on aging nothing will!

http://www.youtube.com/watch%3Fv%3DtQitQH8Fu_8

http://www.youtube.com/watch?v=ntY01qoIdus

⬐ JulianMorrison

In fact, the SENS foundation is ignoring some of those - because medical research is already attacking them as problems in their own right.

⬐ MikeCapone

Yep, SENS isn't duplicating already existing research. If you support them, you are supporting research that might not take place otherwise.

⬐ danielford

That's complicated. My criticism of Aubrey de Grey is one I have of transhumanism in general, which is that it's mostly CS people taking Moore's law and applying it to biological problems without having any experience in biology. Aubrey de Grey's degrees are not in the life sciences, and to my knowledge he's never been directly engaged in a biological research project. Those of us who have done aging research understand how ridiculously difficult it can be to do things that sound simple on paper, and De Grey isn't even making proposals that are simple on paper.

On the other hand, he seems to be a smart, well-intentioned guy who has spent a lot of time developing a theoretical knowledge of how biological systems work. De Grey's not going to spend your money on coke and whores, and he's not going to spend it developing the ultimate power crystal. He's just underestimated the difficulty of solving the problem.

So if you think aging is a disease and not a natural process, it's probably underfunded and you should consider giving him money. Just understand that you're probably going to die of an aging-related complication regardless of how much money you or anyone else gives him.

⬐ DrJohnty

In my opinion conquering aging is pretty much the same a beating any other disease albeit aging is a complex issue involving many different processes. What is comes down to is the realization that there is no magic bullet and that it is a case of chipping away at the root causes and making progress incrementally until we have them all brought to a position where they are manageable. Aging is no different to any other process and we are starting to understand the root causes and the changes which arise as the body ages. I agree that Aubrey makes it sound simpler than it actually is by breaking the causes down to seven factors as set out below but that does not mean that it is not a realistic proposition to render aging a treatable although chronic condition within 25 to 30 years! The key is funding and for more on that check out http://www.methuselahfoundation.org/

As Aubrey points out we have already discovered the seven biochemical processes which are the root cause of aging. The first was discovered in the mid 1950s, the last almost 30 years ago in 1981. The importance of the amount of time that has elapsed since the discovery of the last of the seven is that it took less time to discover the entire list than has passed since and nothing else has been found. Now factor in the massive increase in our knowledge of biology that has taken place over that time and it seems virtually certain that these seven causes are all there are - cure those and you cure aging! The following is the list with potential solutions some of which are either confirmed or where progress is already at an advanced stage.

1. Cell death and atrophy: Treatable with exercise, stem cells, and chemicals which stimulate cell division.

2. Cancerous cells: Theoretically treatable with a type of gene therapy being developed, called Whole Body Interdiction of Lengthening of Telomeres (WILT).

3. Mutant mitochondria: Mutated DNA in the mitochondria causes a number of diseases. These can be prevented by moving the mitochondrial DNA into the cell nucleus, where the rest of the DNA resides.

4. Cell senescence (unwanted cells): Fat cells and other unwanted cruft can be removed surgically, or by stimulating the immune system to attack unwanted cells.

5. Extracellular crosslinks (loss of elasticity): Certain proteins, such as those in cells making up the arteries, become too rigid over time because they bond to each other. These bonds can be broken with certain chemicals (some in clinical trials even today).

6 Extracellular junk: “Plaque” which collects between cells can be eliminated by stimulating the immune system, and/or by using peptides called “beta-breakers.”

7. Intracellular junk: Molecular garbage can be prevented from overwhelming certain cells by introducing enzymes which are known to be effective against such molecules.

In my opinion aging is no different to any other disease and like all diseases aging is ultimately treatable given the requisite technology. We cannot afford to sit back and simply accept that because everyone in history has lived and died we must follow the same patch. It is a mistake to view aging as a fact of life set in stone when science has progressed to the level where we have the ability to begin the search for a cure. We might not be there yet but we are within striking distance of adding 20 or 30 years to our life expectancy and as Aubrey himself points out increases in life expectancy will be incremental and there is not going to be a sudden magic pill which you take and live forever. The essence of the engineering approach advocated by Aubrey is to manage aging, what he proposes is not a cure but a case of repairing the damage that occurs as we age at various intervals and not to stop the process but to allow the aging process to continue and repair the damage as it arises in the same way you maintain a house or car. This engineering approach is a case of taking advantage of improvements in technology as they occur and not to attempt to cure aging in its entirety and it is in this area that people fail to grasp what Aubrey de Grey is seeking to achieve. I recommend the two books below as great reading and all will be revealed!

Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime (Aubrey de Grey and Michael Rae) ISBN-10: 0312367066 ISBN-13: 978-0312367060

Transcend: Nine Steps to Living Well Forever (Ray Kurzweil and Terry Grossman MD) ISBN-10: 1605299561

I would also check out the following regarding Aubrey de Grey http://www.citywire.co.uk/personal/-/retirement/news-and-fea...

and also the following about Ray Kurzweil if this lot does not wet your appetite for joining the war on aging nothing will!

http://www.youtube.com/watch%3Fv%3DtQitQH8Fu_8

http://www.youtube.com/watch?v=ntY01qoIdus

⬐ ugh

Aging certainly is a natural process. So is Aids. I always assumed that a disease can be both and most of time is both. I don’t even know whether it makes sense to define disease with the help of a term like “natural”.

I would define a disease as something which harms people (i.e. curtailing their cognitive or physical abilities) or kills them. Then I exclude a bunch of stuff which has traditionally not been called disease (like accidents, murder, suicide, etc.). Using that definition aging is most definitely a disease.

⬐ sesqu

Well, unless you exclude it, and it's pretty biased not to. I think you need a better definition.

1913 Webster has: 1. Lack of ease 2. An alteration in the state of the body or of some of its organs, interrupting or disturbing the performance of the vital functions, and causing or threatening pain and weakness

Now that does fit aging.

⬐ ugh

Yeah, my definition is not that great, should have thought more about that.

⬐ FlorinAndrei

I don't think there's any debate on the fact that, given enough time, research will eventually figure out how to stop and reverse the changes brought by aging.

The debate is - whether this can be done soon, as opposed to 10000 years from now.

I certainly wish that AdG was right. But is he? I'm not sure. Maybe he is (yay!), maybe not.

⬐ tome

You should also carefully consider the ethical implications of extending human life indefinitely.

⬐ asdflkj

You should first consider ethical implications of being able to cure aging-caused diseases, and choosing not to do so.

⬐ mikedmiked

I've met him and he seems like a crackpot. Extremely nice, gentle and loveable; but a crackpot.

⬐ crystalis

I've met mikedmiked and he seems like a crackpot. Extremely nice, gentle and loveable; but a crackpot.

⬐ MikeCapone

He used to be a lot more controversial a few years ago (Technology Review even had a challenge, asking biogerontologists to debunk his claims, though none really did a convincing job). He's slowly but surely making his ideas more mainstream by tirelessly speaking, debating anyone who wants to, organising conferences and editing a respected peer reviewed journal (Rejuvenation Research, iirc).

If you think you have a good argument that would invalidate his theories, please first make sure that he hasn't answered it a thousand times first.

As usual, Wikipedia has mostly neutral info:

http://en.wikipedia.org/wiki/Aubrey_de_Grey

⬐ jules

What are the results of his research or related research? How much money does he think he'll need to meet his goal?

⬐ reasonattlm

Another line of research that has been progressing since the early days of fundraising (because it was cheap to get started) is the search for bacterial enzymes that can break down the gunk that builds up in your cells with age, and as a consequence destroys the cellular garbage-collection mechanisms. You might have heard of lipofuscin and its effects on autophagy, for example:

http://www.fightaging.org/archives/2009/12/lysosomal-activit...

The links at the bottom of this page outline progress to date - some potential enzymes are found, which could feed into a larger scale project to develop them if funding arrives:

http://www.sens.org/sens-research/research-themes/lysosens

Meanwhile, small scale funding can keep people working on screening bacteria for more enzymes to break down more types of chemical gunk that cause your cellular systems to fail with advancing age.

⬐ FlorinAndrei

"How much money does he think he'll need to meet his goal?"

That question doesn't make a lot of sense. This is not a Web 2.0 startup. It's a lot more fundamental than that, and a lot of the required tools and technologies have not been invented yet - that's what they are trying to do.

⬐ jules

Of course, but he should be able to give a ballpark figure. Are we talking about millions, billions or trillions?

⬐ MikeCapone

afaik, in the millions. Mostly, once enough progress has been made, the money should pour in because people will now know it's possible and demand it.

⬐ reasonattlm

You might look at the mitochondrial work which recently focused on Corral-Debrinski's lab as the most likely prospect for getting the job done. A brief outline is at the end of this page:

http://www.sens.org/sens-research/research-themes/mitosens

and you can look at Corral-Debrinski's breakthrough here:

http://www.ncbi.nlm.nih.gov/pubmed/18771762

Basically it's now shown possible to move a mitochondrial gene into the nucleus and then have the proteins produced pushed back to the mitochondria for use. When done for the 13 important mitochondrial genes whose mutation damages us, then this will make it possible completely remove their contribution to aging.

There is good reason to think that this is a large contribution.

Context:

http://www.fightaging.org/archives/2006/10/how-age-damaged-m...

How much money: $1 billion over ten years to implement SENS fully in mice. Incremental amounts obtain incremental progress.

⬐ borisk

In humans, mitochondria have at least 615 distinct genes. Interestingly how these guys decided only 13 of them are important.

⬐ jules

How much of that money has been donated already? i.e. how much more is needed?

It's interesting stuff. It makes me wonder whether I should be studying biology :)

⬐ reasonattlm

I don't know how much SENS Foundation has raised since it diverged from the Methuselah Foundation. For the period prior to that, you can look at the Methuselah Foundation records:

http://www.mfoundation.org/?pn=mj_donations_funding

http://www.mfoundation.org/?pn=donors

These are just ("just") a few millions - though I'm sure the folk reading HN will appreciate how much work went into raising those funds for a visionary project. By any account, a grand success in putting forward a new idea and bringing on board people who think the same way. Like all grand successes, it's the first step on a much longer path.

(You may or may not know that one of the largest donors is Peter Thiel).

In essence, SENS is still looking for the big hit, the scale up to mid-7-figures. By donating modestly now you add your name to hundreds of others who have already stepped up to help make the ramp needed for that goal.

Indeed, the diseases of aging kill in the range of 100-200k people every single day, while making life miserable for hundreds of millions and negatively impacting the people around these senescent individuals (who here enjoys seeing family and friends get sick and die?). It represents a huge loss of human capital (what if Paul Erdos was still around?), and it costs a huge amount in palliative care that we know ain't going to cure people.

When that is taken into account, the fight against the diseases of aging (actually reversing aging, not just making people live a couple of years more in a senescent state) is incredibly under-funded compared to all kinds of other things.

Vaccines are important, but they're already getting attention. What about saving that kid's life when he's 80 years old? Your dollars make a bigger difference when used doing research in fields that are currently overlooked because aging isn't considered a disease by most (yet).

SENS.org is where I donate most of my charity money.

http://www.ted.com/index.php/talks/view/id/39

and

http://video.google.com/videoplay?docid=8554766938711591377&...

and

http://www.amazon.com/dp/0312367066

for background info.

Please at least read/see those before making the same "it won't work/wouldn't be a good thing" arguments that everybody has made a thousand times when first introduced to this. Thank you.

⬐ tsally

Please at least read/see those before making the same "it won't work/wouldn't be a good thing" arguments that everybody has made a thousand times when first introduced to this. Thank you.

I will do that. Thanks for your informed post.