Longevity Research on Reservatrol 30% lifespan increase

note: I like his thinking, he is breaking the negative thought form about age limits that is currently programming everyone to die at 80. His methods are external tech, which may be helpful, but are way toolimited and slow for me. Qigong and neidangong (alchemy) are the Way to go direct, if karmic issues don’t kill you first….-Michael

BOOTSTRAPPING OUR WAY TO AN AGELESS FUTURE
By Aubrey de Grey
edge.org

http://www.edge.org/3rd_culture/degrey07/degrey07_index.html

………….

AUBREY DE GREY is a biomedical gerontologist and chairman and chief science
officer of the Methuselah Foundation, a VA-based 501(c)(3). He is the author
of some 80 articles and commentaries in peer-reviewed scientific journals,
and of The Mitochondrial Free Radical Theory of Aging. He is coauthor (with
Michael Rae) of Ending Aging: The Rejuvenation Breakthroughs That Could
Reverse Human Aging in Our Lifetime.

Aubrey de Grey’s Edge Bio Page:
http://www.edge.org/3rd_culture/bios/degrey.html

…………..

An important fact is that the therapies we develop in a decade or so in
mice, and those that may come only a decade or two later for humans, will
not be perfect. Other things being equal, there will be a residual
accumulation of damage within our bodies, however frequently and thoroughly
we apply these therapies, and we will eventually experience age-related
decline and death just as now, only at a greater age. Probably not all that
much greater either — probably only 30-50 years older than today.

But other things won’t be equal, and I’m going to explain why not — and
why, as you may already know from other sources, I expect many people alive
today to live to 1000 years of age and to avoid age-related health problems
even at that age.

I’ll start by describing why it’s unrealistic to expect these therapies to
be perfect.

Evolution didn’t leave notes

The body is a machine, and that’s both why it ages and why it can in
principle be maintained. I have made a comparison with vintage cars, which
are kept fully functional even 100 years after they were built, using the
same maintenance technologies that kept them going 50 years ago when they
were already far older than they were ever designed to be. More complex
machines can also be kept going indefinitely, though the expense and
expertise involved may mean that this never happens in practice because
replacing the machine is a reasonable alternative. This sounds very much
like a reason to suppose that the therapies we develop to stave off aging
for a few decades will indeed be enough to stave it off indefinitely.

But actually that’s overoptimistic. All we can reliably infer from a
comparison with man-made machines is that a truly comprehensive panel of
therapies, which truly repairs everything that goes wrong with us as a
result of aging, is possible in principle — not that it is foreseeable. And
in fact we can see that actually one thing about them is very unlike
maintenance of a man-made machine: these therapies strive to minimally alter
metabolism itself, and target only the initially inert side-effects of
metabolism, whereas machine maintenance may involve adding extra things to
the machinery itself (to the fuel or the oil of a car, for example). We can
get away with this sort of invasive maintenance of man-made machines because
we (well, some of us!) know how they work right down to the last detail, so
we can be adequately sure that our intervention won’t have unforeseen
side-effects. With the body — even the body of a mouse — we are still
profoundly ignorant of the details, so we have to sidestep our ignorance by
interfering as little as possible.

What that means for efficacy of therapies is that, as we fix more and more
aspects of aging, you can bet that new aspects will be unmasked. These new
things will not be fatal at a currently normal age, because if they were,
we’d know about them already. But they’ll be fatal eventually, unless we
work out how to fix them too.

Even within each existing category, there are some subcategories that will
be easier to fix than others. For example, there are lots of chemically
distinct cross-links responsible for stiffening our arteries; some of them
may be broken with ALT-711 and related molecules, but others will surely
need more sophisticated agents that have not yet been developed. Another
example: obviating mitochondrial DNA by putting modified copies of it into
the cell’s chromosomes requires gene therapy, and thus far we have no gene
therapy delivery system (“vector”) that can safely get into all cells, so
for the foreseeable future we’ll probably only be able to protect a subset
of cells from mtDNA mutations. Much better vectors will be needed if we are
to reach all cells.

In practice, therefore, therapies that rejuvenate 60-year-olds by 20 years
will not work so well the second time around. When the therapies are applied
for the first time, the people receiving them will have 60 years of “easy”
damage (the types that the therapies can remove) and also 60 years of
“difficult” damage. But by the time beneficiaries of these therapies have
returned to biologically 60 (which, let’s presume, will happen when they’re
chronologically about 80), the damage their bodies contain will consist of
20 years of “easy” damage and 80 years of “difficult” damage. Thus, the
therapies will only rejuvenate them by a much smaller amount, say ten years.
So they’ll have to come back sooner for the third treatment, but that will
benefit them even lessŠ and very soon, just like Achilles catching up with
the tortoise in Zeno’s paradox, aging will get the better of them.

An extremely counterintuitive fact is that, even though it will be much
harder to double a middle-aged human’s remaining lifespan than a middle-aged
mouse’s, multiplying that remaining lifespan by much larger factors — ten
or 30, say — will be much easier in humans than in mice.

The two-speed pace of technology

I’m now going to switch briefly from science to the history of science, or
more precisely the history of technology.

It was well before recorded history that people began to take an interest in
the possibility of flying: indeed, this may be a desire almost as ancient as
the desire to live forever. Yet, with the notable but sadly unreproduced
exception of Daedalus and Icarus, no success in this area was achieved until
about a century ago. (If we count balloons then we must double that, but
really only airships — balloons that can control their direction of travel
reasonably well — should be counted, and they only emerged at around the
same time as the aircraft.) Throughout the previous few centuries, engineers
from Leonardo on devised ways to achieve controlled powered flight, and we
must presume that they believed their designs to be only a few decades (at
most) from realisation. But they were wrong.

Ever since the Wright brothers flew at Kitty Hawk, however, things have been
curiously different. Having mastered the basics, aviation engineers seem to
have progressed to ever greater heights (literally as well as
metaphorically!) at an almost serenely smooth pace. To pick a representative
selection of milestones: Lindbergh flew the Atlantic 24 years after the
first powered flight occurred, the first commercial jetliner (the Comet)
debuted 22 years after that, and the first supersonic airliner (Concorde)
followed after a further 20 years.

This stark contrast between fundamental breakthroughs and incremental
refinements of those breakthroughs is, I would contend, typical of the
history of technological fields. Further, I would argue that it’s not
surprising: both psychologically and scientifically, bigger advances are
harder to estimate the difficulty of.

I mention all this, of course, because of what it tells us about the likely
future progress of life extension therapies. Just as people were wrong for
centuries about how hard it is to fly but eventually cracked it, we’ve been
wrong since time immemorial about how hard aging is to combat but we’ll
eventually crack it too. But just as people have been pretty reliably
correct about how to make better and better aircraft once they had the first
one, we can expect to be pretty reliably correct about how to repair the
damage of aging more and more comprehensively once we can do it a little.

That’s not to say it’ll be easy, though. It’ll take time, just as it took
time to get from the Wright Flyer to Concorde. And that is why, if you want
to live to 1000, you can count yourself lucky that you’re a human and not a
mouse. Let me take you through the scenario, step by step.

Suppose we develop Robust Mouse Rejuvenation in 2016, and we take a few
dozen two-year-old mice and duly treble their one-year remaining lifespans.
That will mean that, rather than dying in 2017 as they otherwise would,
they’ll die in 2019. Well, maybe not — in particular, not if we can develop
better therapies by 2018 that re-treble their remaining lifespan (which will
by now be down to one year again). But remember, they’ll be harder to repair
the second time: their overall damage level may be the same as before they
received the first therapies, but a higher proportion of that damage will be
of types that those first therapies can’t fix. So we’ll only be able to
achieve that re-trebling if the therapies we have available by 2018 are
considerably more powerful than those that we had in 2016. And to be honest,
the chance that we’ll improve the relevant therapies that much in only two
years is really pretty slim. In fact, the likely amount of progress in just
two years is so small that it might as well be considered zero. Thus, our
murine heroes will indeed die in 2019 (or 2020 at best), despite our best
efforts.

But now, suppose we develop Robust Human Rejuvenation in 2031, and we take a
few dozen 60-year-old humans and duly double their 30-year remaining
lifespans. By the time they come back in (say) 2051, biologically 60 again
but chronologically 80, they’ll need better therapies, just as the mice did
in 2018. But luckily for them, we’ll have had not two but twenty years to
improve the therapies. And 20 years is a very respectable period of time in
technology — long enough, in fact, that we will with very high probability
have succeeded in developing sufficient improvements to the 2031 therapies
so that those 80-year-olds can indeed be restored from biologically 60 to
biologically 40, or even a little younger, despite their enrichment
(relative to 2031) in harder-to-repair types of damage. So unlike the mice,
these humans will have just as many years (20 or more) of youth before they
need third-generation treatments as they did before the second.

And so onŠ

Longevity Escape Velocity

The key conclusion of the logic I’ve set out above is that there is a
threshold rate of biomedical progress that will allow us to stave off aging
indefinitely, and that that rate is implausible for mice but entirely
plausible for humans. If we can make rejuvenation therapies work well enough
to give us time to make then work better, that will give us enough
additional time to make them work better still, which will Š you get the
idea. This will allow us to escape age-related decline indefinitely, however
old we become in purely chronological terms. I think the term “longevity
escape velocity” (LEV) sums that up pretty well.

One feature of LEV that’s worth pointing out is that we can accumulate
lead-time. What I mean is that if we have a period in which we improve the
therapies faster than we need to, that will allow us to have a subsequent
period in which we don’t improve them so fast. It’s only the average rate of
improvement, starting from the arrival of the first therapies that give us
just 20 or 30 extra years, that needs to stay above the LEV threshold.

In case you’re having trouble assimilating all this, let me describe it in
terms of the physical state of the body. Throughout this book, I’ve been
discussing aging as the accumulation of molecular and cellular “damage” of
various types, and I’ve highlighted the fact that a modest quantity of
damage is no problem — metabolism just works around it, in the same way
that a household only needs to put out the garbage once a week, not every
hour. In those terms, the attainment and maintenance of escape velocity
simply means that our best therapies must improve fast enough to outweigh
the progressive shift in the composition of our aging damage to more
repair-resistant forms, as the forms that are easier to repair are
progressively eliminated by our therapies. If we can do this, the total
amount of damage in each category can be kept permanently below the level
that initiates functional decline.

Another, perhaps simpler, way of looking at this is to consider the analogy
with literal escape velocity, i.e. the overcoming of gravity. Suppose you’re
at the top of a cliff and you jump off. Your remaining life expectancy is
short — and it gets shorter as you descend to the rocks below. This is
exactly the same as with aging: the older you get, the less remaining time
you can expect to live. The situation with the periodic arrival of ever
better rejuvenation therapies is then a bit like jumping off a cliff with a
jet-pack on your back. Initially the jetpack is turned off, but as you fall,
you turn it on and it gives you a boost, slowing your fall. As you fall
further, you turn up the power on the jetpack, and eventually you start to
pull out of the dive and even start shooting upwards. And the further up you
go, the easier it is to go even further.

The political and social significance of discussing LEV

I’ve had a fairly difficult time convincing my colleagues in biogerontology
of the feasibility of the various SENS components, but in general I’ve been
successful once I’ve been given enough time to go through the details. When
it comes to LEV, on the other hand, the reception to my proposals can best
be described as blank incomprehension. This is not too surprising, in
hindsight, because the LEV concept is even further distant from the sort of
scientific thinking that my colleagues normally do than my other ideas are:
it’s not only an area of science that’s distant from mainstream gerontology,
it’s not even science at all in the strict sense, but rather the history of
technology. But I regard that as no excuse. The fact is, the history of
technology is evidence, just like any other evidence, and scientists have no
right to ignore it.

Another big reason for my colleagues’ resistance to the LEV concept is, of
course, that if I’m seen to be right that achievement of LEV is foreseeable,
they can no longer go around saying that they’re working on postponing aging
by a decade or two but no more. There is an intense fear within the senior
gerontology community of being seen as having anything to do with radical
life extension, with all the uncertainties that it will surely herald. They
want nothing to do with such talk.

You might think that my reaction to this would be to focus on the short
term: to avoid antagonising my colleagues with the LEV concept and its
implications of four-digit lifespans, in favour of increased emphasis on the
fine details of getting the SENS strands to work in a first-generation form.
But this is not an option for me, for one very simple and incontrovertible
reason: I’m in this business to save lives. In order to maximise the number
of lives saved — healthy years added to people’s lives, if you’d prefer a
more precise measure — I need to address the whole picture. And that means
ensuring that the general public appreciate the importance of this work
enough to motivate its funding.

Now, your first thought may be: hang on, if indefinite life extension is so
unpalatable, wouldn’t funding be attracted more easily by keeping quiet
about it? Well, no — and for a pretty good reason.

The world’s richest man, Bill Gates, set up a foundation a few years ago
whose primary mission is to address health issues in the developing world.
This is a massively valuable humanitarian effort, which I wholeheartedly
support, even though it doesn’t directly help SENS at all. I’m not the only
person who supports it, either: in 2006 the world’s second richest man,
Warren Buffett, committed a large proportion of his fortune to be donated in
annual increments to the Gates Foundation.

The eagerness of extremely wealthy individuals to contribute to world health
is, in more general terms, an enormous boost for SENS. This is mainly
because a rising tide raises all boats: once it has become acceptable (even
meritorious) among that community to be seen as a large-scale health
philanthropist, those with “only” a billion or two to their name will be
keener to join the trend than if it is seen as a crazy way to spend your
hard-earned money.

But there’s a catch. That logic only works if the moral status of SENS is
seen to compare with that of the efforts that are now being funded so well.
And that’s where LEV makes all the difference.

SENS therapies will be expensive to develop and expensive to administer, at
least at first. Let’s consider how the prospect of spending all that money
might be received if the ultimate benefit would be only to add a couple of
decades to the lives of people who are already living longer than most in
the developing world, after which those people would suffer the same
duration of functional decline that they do now.

It’s not exactly the world’s most morally imperative action, is it?

Indeed, I would go so far as to say that, if I were in control of a few
billion dollars, I would be quite hesitant to spend it on such a marginal
improvement in the overall quality and quantity of life of those who are
already doing better in that respect than most, when the alternative exists
of making a similar or greater improvement to the quality and quantity of
life of the world’s less fortunate inhabitants.

The LEV concept doesn’t make much difference in the short term to who would
benefit from these therapies, of course: it will necessarily be those who
currently die of aging, so in the first instance it will predominantly be
those in wealthy nations. But there is a very widespread appreciation in the
industrialised world — an appreciation that, I feel, extends to the wealthy
sectors of society — that progress in the long term relies on aiming high,
and in particular that the moral imperative to help those at the rear of the
field to catch up is balanced by the moral imperative to maximise the
average rate of progress across the whole population, which initially means
helping those who are already ahead. The fact that SENS is likely to lead to
LEV means that developing SENS gives a huge boost to the quality and
quantity of life of whomever receives it: so huge, in fact, that there is no
problem justifying it in comparison the alternative uses to which a similar
sum of money might be put. The fact that lifespan is extended indefinitely
rather than by only a couple of decades is only part of the difference that
LEV makes, of course: arguably an even more important difference in terms of
the benefit that SENS gives is that the whole of that life will be youthful,
right up until a beneficiary mistimes the speed of an oncoming truck. The
average quality of life, therefore, will rise much more than if all that was
in prospect were a shift from (say) 7:1 to 9:1 in the ratio of healthy life
to frail life.

Quantifying longevity escape velocity more precisely

I hope I have closed down the remaining escape routes that might still have
remained for those still seeking ways to defend a rejection of the SENS
agenda. I have shown that SENS can be functionally equivalent to a way to
eliminate aging completely, even though in actual therapeutic terms it will
only be able to postpone aging by a finite amount at any given moment in
time. I’ve also shown that this makes it morally just as desirable —
imperative, even — as the many efforts into which a large amount of private
philanthropic funding is already being injected.

I’m not complacent though: I know that people are quite ingenious when it
comes to finding ways to avoid combating aging. Thus, in order to keep a few
steps ahead, I have recently embarked on a collaboration with a stupendous
programmer and futurist named Chris Phoenix, in which we are determining the
precise degree of healthy life extension that one can expect from a given
rate of progress in improving the SENS therapies. This is leading to a
series of publications highlighting a variety of scenarios, but the short
answer is that no wool has been pulled over your eyes above: the rate of
progress we need to achieve starts out at roughly a doubling of the efficacy
of the SENS therapies every 40 years and actually declines thereafter. By
“doubling of efficacy” I mean a halving of the amount of damage that still
cannot be repaired.

So there you have it. We will almost certainly take centuries to reach the
level of control over aging that we have over the aging of vintage cars —
totally comprehensive, indefinite maintenance of full function — but
because longevity escape velocity is not very fast, we will probably achieve
something functionally equivalent within only a few decades from now, at the
point where we have therapies giving middle-aged people 30 extra years of
youthful life.

I think we can call that the fountain of youth, don’t you?

…………….

[Excerpted from Ending Aging: The Rejuvenation Breakthroughs That Could
Reverse Human Aging in Our Lifetime by Aubrey de Grey with Michael Rae, St
Martin’s Press, 2007.]