[extropy-chat] Anti-Aging Molecule Discovered

[The Avantguardian]

--- Robert Bradbury <robert.bradbury at gmail.com> wrote:

> On 6/12/06, Ian Goddard <iamgoddard at yahoo.com>
> wrote:
> >
> > Suppose a drug is found that reverses aging.
> 
> 
> All they are claiming is a removal of cells from the
> "senescent" state they
> are not claiming "reversing aging".

True. The spin-doctored cheese was almost too thick to
stomach. But those guys did a lot of hard work so I
guess they deserve some media attention.
 
> The first
> sentence in their abstract is
> questionable because most somatic cells are not
> replicating and are not
> "senescent" in the classical sense.

Yes. In their abstract they do not dilineate the
difference between reversible growth arrest i.e.
quiescence from irreversible growth arrest i.e.
senescence. But they DO demonstrate that what they are
doing is transiently reversing senescence. The
SA-beta-galactasidase assay and cell morphology data
is convincing that these cells are indeed senescent.  


>Senescence is
> classically determined
> using cells which replicate and then cease
> replication but do not undergo
> cell death (apoptosis).

I am not sure what you mean by classically. (Leonard
Hayflick?) But these days senescence is viewed as
termination of the replication program due to the cell
sensing that it may be on the verge of becoming
cancerous due to dysfunctional telomeres (either too
short or the wrong shape), DNA damage by radiation or
free radicals, or overly strong mitogenic stimulation
(growth signals).
  
> 
> However, all they seem to have so far are
> cell-culture tests of a drug, and
> > there's a big leap from in-vitro to in-vivo
> outcomes.  There might even be
> > reasons why preventing cellular senescence is not
> universally beneficial to
> > a whole biological system.

Ian is correct here. I don't think this drug will be
useful for systemic use (in a pill for example) but it
may have clinical application as a topical or local
treatment such as an ointment to help wound healing in
elderly or diabetic patients. It could also be useful
to grow up ex vivo cells into tissues that are then
grafted back into people. I would be interested to see
what effects it has on cells such as neurons and heart
muscle cells for example. I would also like to see
what effects it has on telomerase expression and
telomere length.    
 
> Well said.  Indeed, if the alternatives to
> senescence are apoptosis or
> cancer, then senescence is clearly the better of the
> three.

That is the whole purpose of senescence: a compromise
between cancer and apoptosis that lets a potentially
damaged cell to survive and continue to do its job
while prohibiting it from replicating. The key to this
drug is that it can temporarily suspend that
prohibition. 

  And indeed the
> ATM gene that their CGK733 is affecting is a
> critical DNA repair gene which
> when mutated results in either a reduction in cell
> division or an increased
> risk of cancer.  The two primary genes it interacts
> with are p53 and BRCA1
> [1], mutations in which increase cancer risks.  So I
> would suspect that
> interfering with ATM such that it reduces cellular
> senescence would increase
> cancer.

The drug is reversible, so taking the drug away seems
to re-establish senescence. The question is how many
additional cell divisions can a senescent cell
tolerate before it becomes faulty enough to cause
cancer.
 
> This is the kind of report is what happens when you
> have individuals who are
> not educated in the biology of aging extending their
> claims into that
> swamp.

Whom are you refering to? The researchers or the press
agents? A lot of confusion is always caused by the
Madison Ave. types who get a hold of some information
like this. All in an effort to generate investment. I
think generally the researchers themselves are often
less culpable than the marketing gurus they hire. 

> Their abstract is pretty conservative
> (sticking to the facts) but I
> have no doubt that people unfamiliar with the field 
> (i.e. the general press
> & public) will misinterpret this as a significant
> breakthrough.

It has the potential to be as significant a
breakthrough as the "purple pill" and every other drug
pharmaceuticals convince doctors to prescribe and the
public to buy. The mantra of the modern pharmaceutical
industry seems to be find a chemical that does
SOMETHING physiologically and then invent a disease or
disorder that creates a percieved need for the drug in
question.

The REAL breakthrough is their MAGIC (corny name I
know) technology. I imagine every big pharmaceutical
will either license it or reverse engineer it sooner
or later. It really is a great way to do mass
throughput screening for small molecular inhibitors of
known protein targets. I am thouroughly impressed by
it.


Stuart LaForge
alt email: stuart"AT"ucla.edu

"What I am going to tell you about is what we teach our physics students in the third or fourth year of graduate school... It is my task to convince you not to turn away because you don't understand it. You see my physics students don't understand it... That is because I don't understand it. Nobody does." - Richard Feynman on QM

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