
A New—and Reversible—Cause of Aging - DiabloD3
http://hms.harvard.edu/news/genetics/new-reversible-cause-aging-12-19-13
======
jusben1369
“The aging process we discovered is like a married couple—when they are young,
they communicate well, but over time, living in close quarters for many years,
communication breaks down,” said Harvard Medical School Professor of Genetics
David Sinclair"

\- Totally off topic though but I think he's describing a couple heading to
divorce. Nearly all successful marriages move in the exact opposite direction.

~~~
grok2
I think, it's not really that communication breaks down, it is more that you
don't need to communicate at all because you know the other person so well by
now. Then divorce happens because you don't like what you know or you realize
your spouse isn't what you wanted, or the marriage becomes stronger because
you anticipate your partners needs/actions without having to communicate. So
yeah, the analogy is not really right.

~~~
DigitalJack
While it is true that you learn your spouse that well, it will be long before
that when you realize if don't like them.

However when you don't communicate, your lives get out of sync. At some point
this has gone on long enough, the changes we go through (called life) cause
people to become strangers again.

It's like two inertial systems. They drift, differently, over time and this
difference accumulates. Communication between the two inertial units can
synchronize them. Or a trusted third party (GPS) can give them both a course
correction.

~~~
agumonkey
So I was supposed to be my parents GPS.

------
edj
Link to the abstract on PubMed:
[http://www.ncbi.nlm.nih.gov/pubmed/24582957](http://www.ncbi.nlm.nih.gov/pubmed/24582957)

Original is behind a paywall.

\---

I'd take all this with a grain of salt, though. The biology of aging is
incredibly complex. Seemingly certain answers to the question of what causes
or mediates aging (e.g. free radicals) have turned out to be less conclusive
and all-explaining than researchers originally thought.

~~~
stcredzero
There are seven distinct mechanisms for cellular and intracellular damage
resulting from aging. Improving the regulation of mitochondria could
completely fix one and slow down the rate of accumulation of a few other types
of damage, but that's it.

[http://en.wikipedia.org/wiki/Strategies_for_Engineered_Negli...](http://en.wikipedia.org/wiki/Strategies_for_Engineered_Negligible_Senescence#Types_of_aging_damage_and_treatment_schemes)

~~~
pyduan
Please note that Aubrey de Grey's theories are highly controversial and while
some of these mechanisms are indeed big topics in the field, many
biogerontologists have been publicly skeptical of his claims. In fact, some of
these are even mentioned in your link.

The way you worded it, it seems you're implying SENS is a widely accepted
theory, while in fact it's anything but (although I'd say it certainly is
interesting and worthy of investigation).

~~~
exratione
If by "highly controversial" you mean "supported by many leading names in the
research community" then sure. See this, and note the presence of George
Church, Judith Campisi, Maria Blasco, etc:

[http://sens.org/about/leadership/research-advisory-
board](http://sens.org/about/leadership/research-advisory-board)

The SENS Research Foundation has a yearly budget about a tenth of that of one
of the largest aging research labs, the Buck Institute. The Foundation funds
work in a range of laboratories around in the US and Europe, and has
collaborations with Oxford, Wake Forest, and so forth.

Insofar as controversy exists, you might look on it as a facet of the present
dispute over modern theories of aging: camps for aging as accumulated damage
versus aging as evolved programming. The accumulated damage side is much
bigger but split into several factions, one of which is centered around SENS.

------
ChuckMcM
Its a promising result, but a lot of mice experiments don't have the same
effects on people. It would be ironic if this technique failed on humans
subjected to a lot of exposure to botox :-) The fear is that suddenly not only
would the rich get richer, but they would never die. That leads to some fairly
depressing scenarios.

~~~
ashray
The rich would not get richer. They would stay alive and stick around until
they got poorer and eventually died.

~~~
stcredzero
In Larry Niven's _Known Space_ books, some of the rich stuck around so long
that they became hyper bored and so decided to become super criminals. He has
one such minor character who is a woman over two centuries old, with all of
the experience and knowledge that entails, with the body of an 18 year old.

~~~
X4
Asked a buddy who ain't that smart on what he would do, if he could live 300
years.

He said: "I'd rob a bank, big time."

I asked why he would do that and he said that he could give the money to a
trustee and sit his time and become rich afterwards.

So your story sounds legit to me. And I just asked for 300 years. Living
16.000 years like in the movie: "The man from Earth", was way out of his
graspable zone. And he started arguing about god would kill you and so on...

~~~
alanfalcon
When you rob a bank and get caught, they don't let you keep the money.

------
chunky1994
Here's a link to the newscientist article on the same discovery:
[http://www.newscientist.com/article/dn24784-turning-back-
tim...](http://www.newscientist.com/article/dn24784-turning-back-time-ageing-
reversed-in-mice.html#.UzcLd63qe0Y)

And the actual paper (the full paper is behind a paywall):
[http://www.cell.com/cell/abstract/S0092-8674(13)01521-3](http://www.cell.com/cell/abstract/S0092-8674\(13\)01521-3)

~~~
jarradhope
Found paper: [http://www.cnd.mcgill.ca/~ivan/age-reversing-
compound.pdf](http://www.cnd.mcgill.ca/~ivan/age-reversing-compound.pdf)

~~~
ackydoodles
Thank-you for that. Reading now. So far it looks like good science.

------
lutusp
Here's a better article that describes the same work:
[http://hms.harvard.edu/news/genetics/new-reversible-cause-
ag...](http://hms.harvard.edu/news/genetics/new-reversible-cause-
aging-12-19-13)

Less hype, more technical detail.

------
salimmadjd
Anti-aging divide? I'm all for anti-aging, I was obsessed by it since my teens
and got a degree in molecular biology thinking I want to dedicate my life to
it, I even own dontage.com.

However, I'm concerned about implications of potentially high-price anti-aging
treatments. Till now, death has been the great equalizer. Life is inherently
unfair. If you are born in poverty there is high chances you'll stay there,
but at least you always count on everyone dying at the end.

With high-price anti-aging treatments people who have wealth can live longer
(maybe one day indefinitely) and accumulate more wealth and those without
money will just dye twice or three times as fast with no way out of the cycle.
You can argue historically we always had this type of divides, for example in
early stages of invention of antibiotics or vaccines or ability to buy them in
black market in areas where they were scarce. However, we're moving from
preventing premature deaths to extending life beyond its natural extension and
that brings a whole new set of issues.

Will there be enough retirement funds? If we do democratize anti-aging
treatments, lets say increasing the average life span to 100 or 120. Will
there be enough funding? As is, the social security is feeling the pressures
of increased average life-span. So if we are able to make a 60 year olds be 20
(in some aspects of aging) or 90 year old to 30 and as the article alluded to,
decrease the risk of cancers (perhaps). Then, who will pay to cover the
retirement funding gap?

We're heading toward a world were you can choose to live longer and have the
wealth to support your life for extended time, and those who will only live
1/2 or 1/3 as much just because they were born in a different household.

Among all the technological breakthroughs, anti-aging will probably have the
biggest social impact and as a society we're not even thinking about it or are
even preparing for it yet. But then again, if you have the money, why should
you care.

~~~
ggreer
There are many downsides to curing aging, but none of them are as bad as the
current situation: 100,000 deaths every day. It's worse than you can imagine;
those 100,000 people experienced decades of mental and physical decline before
they died.

I think you are confused about the economics of the situation. Who will pay
for retirement benefits? Aging is _why_ we retire. If we never got old, we
could work as long as we wanted.

Even if anti-aging treatments remain expensive for decades after they're
invented, it will still be economically worthwhile to treat everyone. This is
because age-related diseases are more expensive. Alzheimer's. Cancer. Heart
disease. Dementia. COPD. These diseases slowly kill their victims, causing
immense suffering. Treatments for most of them are ineffectual and cost
millions for each patient. When it comes to cost, rejuvenation therapies have
a low bar to get over.

My grandmother died this month. She had a form of rheumatoid arthritis that
slowly turned her lungs into scar tissue. My only consolation is that her mind
didn't go before she died. If only rich people could avoid her fate, I
wouldn't mind a bit. The fewer people who suffer as she did, the better.

~~~
eli_gottlieb
>I think you are confused about the economics of the situation. Who will pay
for retirement benefits? Aging is why we retire. If we never got old, we could
work as long as we wanted.

Completely backwards. "We're old and can't work anymore" is the excuse used to
publicly justify finally being allowed not to work anymore in a Calvinist-
capitalist culture. What we actually want is to _minimize_ the portion of our
lifespan spent working for mere wages.

Mind, one reason I've come to support anti-aging and automation advancements
is _davka_ that they force our culture to actually confront these issues, that
they "heighten the contradictions" as we Marxists say, rather than pretending
everything's fine and letting the system get away with its sins.

------
simonsquiff
One thing I'd really like to understand re: ageing is why a newborn is
essentially 'reset' from an ageing perspective. I appreciate that egg cells
aren't constantly dividing during a mothers life but they are still a product
of division and contain DNA that can suffer from time based mutations. So if
aging is due to mistakes accumulated during either divisions or time then why
are children born young? I don't think this is as simple as non-viable embryos
are miscarried, there must be something different in the formation of embryos
that means they don't carry the aging of their parents...and what clue does
that give to cure aging?

~~~
hughlomas
The organism is a vessel to propagate the genes. Germ cells such as embryos
usually have additional defenses and repair mechanisms, such as for DNA
damage, that the somatic cells lack. Since the soma are merely there to help
the replication of the germ line, they receive less investment.

No creature we know of has successfully evolved the capability to permanently
stave off aging. Besides the inevitable issues with fighting entropy in a
complex system, how would an ageless organism compete in the shifting
landscape of an ecosystem as other creatures evolve around it? How would a
non-aging organism adapt? It seems likely that continually creating new
generations is the best strategy for genetic replication.

Now we are at the amusing point that genes may have unwittingly experienced
their own skynet event. Modern science has given us the ability to not only
gaze upon our creators, but manipulate them to do the bidding of ideas.

~~~
simonsquiff
Thanks - germ cells was the key term I was missing, this section on the
germline on Wikipedia answers my original question:

Germline cells are immortal, in the sense that they have reproduced
indefinitely since the beginning of life. This is largely due to the activity
of the enzyme known as telomerase. This enzyme extends the telomeres of the
chromosome, preventing chromosome fusions and other negative effects of
shortened telomeres. Most somatic cells, by comparison, can only divide around
30-50 times according to the Hayflick limit. Certain somatic cells, known as
stem cells, also express telomerase and are potentially immortal.

~~~
Houshalter
So then why can't we just inject ourselves with that enzyme and be immortal?

------
WasimBhai
For those working in Genetics, how much is the field upbeat about regenerative
medicine in general, and Google's Calico [0] venture in particular?

[0]
[https://plus.google.com/+LarryPage/posts/Lh8SKC6sED1](https://plus.google.com/+LarryPage/posts/Lh8SKC6sED1)

------
exratione
Many of the problems surrounding funding of meaningful efforts to treat aging,
eliminate age-related disease, and extend healthy life come about because the
people with the biggest megaphones are also doing the least useful work.

This is true outside the scientific community, in the "anti-aging" marketplace
that tries to convince people they should take supplements rather than support
research.

This is true inside the scientific community, where the Sinclair labs and
their work on sirtuins - which is about as useless as supplements based on the
last ten years of work - get far more attention than anything that is actually
likely to produce meaningful results.

This article is an example of high-road hype and nonsense. More than a decade
of work on sirtuins have failed to reliably produce even a tiny fraction of
the gains to health and life provided by calorie restriction or exercise. This
is just one tiny slice of the broader mainstream scientific approach of
attempting to alter the operation of metabolism in order to provide benefits.
This is vastly complex, and will take a very, very long time to get anywhere.
When scientists speak of not seeing any real progress towards human longevity
in the near future, this is the approach they are talking about: take this
thing, the interaction space of metabolism with aging, which is vast, and
about which nowhere near enough is understood, and then try to make a better
version of it.

Sure, it's possible in the long term. But we'll all be old before anyone even
makes a good first pass through this enormous complexity.

Yet there is a much better path forward towards treatment of aging. This is to
identify the differences between old and young tissues, something that has
already been done and agreed upon by the scientific community, more or less
settled for the past 20 years, and then fix them all. You don't need to delve
into the interaction space to understand why or how or process or progress.
You just fix it. It is the difference between repainting a wall versus
understanding the deep molecular interactions of wall, paint, and weather so
that you can build a better lasting paint. One of those choices is evidently
much more efficient than the other.

When it's a wall, who cares? Let the paint scientists get on with it. But in
the case of aging, tens of millions of lives are lost every year that passes
while the mainstream screws around with metabolism to slow aging rather than
building the means to repair the identified causes of aging.

Even better, while the metabolic engineers have no clear plan to produce a
good end state, just a bunch of plans that have not yet panned out as expected
despite great expense, the "just fix it" approach to aging has clear paths to
the development of repair therapies for each identified difference between
young and old tissues. So they are only limited in progress by funding.

Why does this situation exist? I blame regulation. If your work doesn't result
in something that looks like a drug, sounds like a drug, and walks like a drug
it isn't going to be approved. Further, treating aging is not a result
recognized by the FDA - so whatever you do has to be sidelined to treat some
disease of aging. In other words only applied after it's too late to prevent
things from going awry. So we see marginal unambitious work on marginal
unambitious treatments, the continuing random walk through the natural world's
pharmacology in search of chemicals that can be crudely administered to do
slightly more good than harm, because that's the only way to have even a
slight chance of getting to market. Highly regulated systems perpetuate their
current state at all expense, and treat change as a threat.

The treatments for aging that might actually do some good in the future are
radically different from today's pharmacology. These are the repair
strategies: mitochondrial gene therapy, adapted bacterial enzymes let loose in
the body, targeted destruction of stem cells and immune cells run wild, that
sort of thing. You can find them described if you look up SENS, the strategies
for engineered negligible senescence, but there are other similar lists put
forward by different research groups. The repair approach is the disruptive
newcomer to the field, barely ten years old, but gathering support. We should
hope that it soon wins over the mainstream, and relegates the era of paying
billions for sirtuin research and other dead-ends to the dustbin of history.

~~~
haldujai
Spoken like a pragmatist and not a scientist. Your argument is the equivalent
of arguing no one should bother with low level programming knowledge or
understanding how functions work in Ruby/Python/etc.

You're also talking like someone who has no experience with life sciences
research at all and is an armchair expert. As someone who has dedicated a
significant portion of my life and time to research in medical sciences it's
not as easy as "fix them all." How do you 'fix' changes in protein expression
without causing unintended side effects? It's hard enough to get something to
work in cell culture let alone in a complex organism where compensatory
mechanisms kick in whenever you do anything. We can't even get mild pain
relief to work without side effects and you're talking about complex tissue
engineering.

SENS is controversial at best (and utter bullshit in the eyes of many), I
wouldn't go around touting it as the future of anti-aging research.
Additionally caloric restriction has recently been shown to not work in humans
and the early gains reported haven't translated well at all. Exercise is
really the only potentially viable strategy you have mentioned.

While academia, especially at top tier institutions and mega-labs, is flawed,
I would caution you to avoid jumping to conclusions because the pace of
research is not to your liking. This isn't, as you so eloquently put it,
painting a wall, it's a very complicated (and new) field that we still know
very little about and are discovering new pitfalls every day.

Edit: Grammar

~~~
exratione
Working to do something about aging in advance of full understanding of aging
is absolutely the pragmatic approach. It is engineering. It is the building of
fine bridges by Romans and Victorians in advance of material science and
computer simulation.

To pick one example from the SENS portfolio - by which I mean the list of
techniques developed in the scientific community for other reasons and adopted
as useful by the SENS proponents - allotopic expression of mitochondrial genes
is absolutely a way to fix protein expression issues. It is the delivery of
proteins to rescue mitochondrial function. It has been demonstrated to work in
mice with no side effects for a gene associated with LHON by two separate
research groups now, neither of which were affiliated with the SENS Research
Foundation when they started out.

This is serious science. You might not like it or be familiar with it, but
you're missing out.

SENS is supported by a number of noted figures in the life sciences, including
George Church, Anthony Atala, Judith Campisi, and so forth:

[http://sens.org/about/leadership/research-advisory-
board](http://sens.org/about/leadership/research-advisory-board)

There are detailed proposals for the development of therapies involved in
SENS. These can be critiqued on their details. For example, allotopic
expression of mitochondrial genes can be critiqued based on what has been
done, the plans for the other genes, and how it is going so far.

You are behind the times on calorie restriction research. It works very well
on all measures of health in primates except for longevity. That is the big
puzzle in calorie restriction: how to explain this disparity, which ties in to
explaining why humans live for an unusually long time. See this paper by
Fontana:

[http://impactaging.com/papers/v5/n7/full/100581.html](http://impactaging.com/papers/v5/n7/full/100581.html)

In general calorie restriction seems better than exercise if you are going to
pick one or the other, which would be foolish of course. Do both. But don't
expect it will help you be one of the 25% who survive past age 90, because the
only thing likely to get you there is an early implementation of SENS. Unless
the programmed aging camp is right, in which case there is nothing that can be
produced in time to greatly help us. But given that implementing SENS is cheap
in comparison to drug development - $1 billion and 20 years to get it working
in mice - what's there to lose?

~~~
haldujai
"It is the building of fine bridges by Romans and Victorians in advance of
material science and computer simulation."

Not really - it is the equivalent of Romans building bridges by sticking dirt
together without figuring out the correct composition of building materials,
why/how materials can cement, and so forth.

"allotopic expression of mitochondrial genes is absolutely a way to fix
protein expression issues."

You are actively presenting bleeding edge research as a definite solution in
spite of how primitive it is [1]. It is not immediately clear that allotopic
expression is the answer, just because it worked in mice for one specific
example it is not necessarily true that it translates to humans or other
diseases. In fact, findings in mice often do not translate to humans [2].

"SENS is supported by a number of noted figures in the life sciences,
including George Church, Anthony Atala, Judith Campisi, and so forth:"

While I respect Campisi's work on senescence and aging there is obviously
conflict here where one of the pioneers of the field is supportive of a theory
that promotes her field. For this reason I think it is best that we do not
defer to authority figures on this matter as you will find reputable
authorities on both sides of this debate.

"You are behind the times on calorie restriction research. It works very well
on all measures of health in primates except for longevity."

See [3] from de Cabo's group (who is one of the authors on the paper in the
OP). If you're talking about increasing lifespan (one of the lofty goals of
SENS) is longevity not the most important thing here? From this (respected)
paper de Cabo points out many flaws in the studies on caloric restriction due
to differing methodologies and genetic variation that resulted in adverse
effects in some murine experiments. This is far from 'working well'.

[1]
[http://www.genetics.org/content/165/2/707.short](http://www.genetics.org/content/165/2/707.short)
[2]
[http://www.pnas.org/content/early/2013/02/07/1222878110.abst...](http://www.pnas.org/content/early/2013/02/07/1222878110.abstract)
[3]
[http://www.nature.com/nature/journal/v489/n7415/full/nature1...](http://www.nature.com/nature/journal/v489/n7415/full/nature11432.html)

------
FD3SA
For the biologically inclined, I sincerely recommend reading this paper in
full. It has a number of extremely groundbreaking hypothesis, which bring
together the common elements of cancer, caloric restriction, and aging.

I find it interesting that this finding suggests that free radical/reactive-
oxygen-species theories of aging were close, but just off the mark. It appears
that the cell can cope quite well with chemical damage of this type, but has a
harder time regulating mtDNA expression, which leads to the same result:
reduced mitochondria function with age.

------
etiam
There was also this interview with Australian ABC around the publication of
the article. [http://www.abc.net.au/news/2013-12-20/researchers-reverse-
sy...](http://www.abc.net.au/news/2013-12-20/researchers-reverse-symptoms-of-
aging-with-1-week/5168582)

Apparently the video has "expired" so please refer to e.g.
[http://www.filedropper.com/researchersreversesymptomsofagein...](http://www.filedropper.com/researchersreversesymptomsofageingwith1weekoftreatmentnewsaustralianbroadcastingcorporationnolbageingx20125)
for that (as an aside, I'd appreciate advice about less obtrusive file upload
services)

------
BetterLateThan
Mr Stoyte broke the silence. 'How long do you figure it would take before a
person went like that?' he said in a slow, hesitating voice. 'I mean, it
wouldn't happen at once ... there'd be a long time while a person ... well,
you know; while he wouldn't change any. And once you get over the first shock
- well, they look like they were having a pretty good time. I mean in their
own way, of course. Don't you think so, Obispo?' he insisted.

\- Aldous Huxley, After Many a Summer Dies the Swan.

...But I am sure this news makes banks, bureaucracies and big pharma mega-
ecstatic.

------
diminoten
Link to the submitted article (before it was changed by an admin), for
posterity's sake: [http://guardianlv.com/2014/01/ageing-successfully-
reversed-i...](http://guardianlv.com/2014/01/ageing-successfully-reversed-in-
mice-human-trials-to-begin-next/)

Dunno why the submission was changed, I suspect the admin didn't actually read
the article, which contains original journalism work (article writer got in
touch with David Sinclair again for an additional quote).

------
X4
Without being an expert in the area, but having some detailed knowledge in the
field, it honestly sounds like hype. The statement that it wasn't mentioned
anywhere, before is bogus. Take a look at the source [1] that describes how
NAD actually has an effect on telomeres.

They really suggest using regular supplements on that url, which I'd call
bullshit! I can't tell, if it's the editors fault, a missunderstandin, or if
they really mean that. That's because I've no access to the real paper.

\--

[1]
[http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleoti...](http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide#Non-
redox_roles)

------
lettergram
The article did not say if the mice lived significantly longer...

------
cmollis
the great irony of cancer cells is that they themselves are immortal.. bit of
poetry and sarcasm on the Creator's part.

------
mcarter
The font size on that page is a reversible cause of ageing.

------
lawl
This is _REALLY_ scary if you have recently read the following article:

 _Could we condemn criminals to suffer for hundreds of years? Biotechnology
could let us extend convicts ' lives 'indefinitely'_

[http://www.dailymail.co.uk/sciencetech/article-2580828/Could...](http://www.dailymail.co.uk/sciencetech/article-2580828/Could-
soon-create-hell-EARTH-Biotechnology-let-extend-criminals-lives-makes-
suffering-HUNDREDS-years.html)

Edit: Since people have some issues with the dailymail, feel free to pick any
other article on this topic:

[https://encrypted.google.com/search?q=prison+life+prolonging](https://encrypted.google.com/search?q=prison+life+prolonging)

I just googled and dailymail appeared at the top. Not sure if that was the
article i read a few weeks ago.

Also please note that I don't want to stiffle innovation in this area in any
way. I think it's awesome research. But I also find it interesting to explore
other "applications" of this technology.

~~~
tormeh
Quoting the Daily Fail? Seems unwise. Not even going to read it and neither
should anyone else.

~~~
lawl
I'm not sure why that would be?

The idea is out there... Speculating if it will happen is pointless anyways,
as it will probably take a long time before reversing aging could be done on
scale.

So I really don't understand the downvote(s).

~~~
bmadden
Your original post is a huge tangent from the topic of discussion. That
article is pure fearmongering and is exactly the type of propagandized
information that stifles innovation.

Obviously it makes sense to talk about the ramifications of new technology,
but the article you linked is doing this in a heavy-handed way to get people
to read the article. The result is disproportionate value being placed on that
idea for the average reader of dailymail, which necessarily detracts from the
discussion of balance surrounding this research.

~~~
vixen99
No article stifles innovation unless some idiot reads it as scripture!

Meanwhile what do you know about the average Daily Mail reader? Presumably
you've researched the around 70 million readers (an exaggeration to be sure
but it's a lot of people) who take a daily look at this popular newspaper. I
rather think not. But that doesn't stop people like you making predictable and
patronizing observations of this kind at every opportunity. No need to
comment. We can all 'read' and draw our own conclusions.

~~~
bmadden
I'm lumping "average daily mail reader" with average person. Surely you are
not ignorant to the effects that propaganda can have on the population. The
linked article does nothing but narrowly discuss one possible consequence of
this type of technology in a manner meant to illicit fear or general negative
association. This is by definition propaganda and it detracts from a
thoughtful analysis of the larger topic of discussion. I'm not patronizing
anyone by drawing attention to the idea that plenty of people use news
articles as end points for information; I'm simply drawing the connection
between that phenomenon and the type of biased reporting seen in the article
above.

