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Are AGEs and Lipofuscin related? Could ALT-711 eliminate lipofuscin?

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Jan 9 08:51:26 EST 1999


William wrote:

> Perhaps it would be a good idea to find out which aspects of the aging
> process cause harm at the same rate early and late in life. Then we
> could possibly compare the two sets of aspects of the aging process
> and figure out exactly why some of them accelerate as we grow older
> and which ones occur at a gradual rate all through life.

Absolutely right.  I'm reminded of a posting from James several months
ago:

> >So, pretend you just did a chip-based aging experiment to gather gene
> >expression data on 10,000 genes at once.  You saw a few hundred go up,
> >and a few hundred go down.  If you had to analyze this type of data,
> >would would you be interested in knowing about it and why?

to which I said:

> I'd like to know which ones varied more linearly and which ones more
> exponentially.

later simplified to:

> forget about old people. .... Characteristics that distinguish a
> 50-year-old from an 80-year-old but do not distinguish a 20-year-old
> from a 50-year-old are presumably downstream effects, so I would be
> less interested in them than in the ones that distinguish a 20-year-old
> from a 50-year-old

With any luck he's doing it as I write!

> I looked up both lipofuscin and advanced glycation end-products on
> medline and found the following few abstracts linking the two
> substances together.

Well found.  The BBRC paper, which I hadn't previously seen, is both the
most recent and the most useful of the ones you posted, because, as they
say, "We demonstrate FOR THE FIRST TIME that lipofuscin is constituted
not only of lipid peroxidation products but also from glycation products".
(The earlier ones, as you see, discuss this only as a possibility; the
letter is about diabetics so is of more limited significance to normal
aging.)  This doesn't imply that an AGE-breaker would NECESSARILY break
up lipofuscin, of course, since the non-AGE crosslinks (from oxidation
reactions) may be enough to hold it together anyway; also, something
that breaks AGE links in the extracellular space may not be able to get
into lysosomes (which is where lipofuscin is) or, if it can, it may then
be destroyed too quickly by the lysosomal machinery.  But I completely
agree with you that any and every promising-looking AGE-breaker should
definitely be tested for its ability to disaggregate lipofuscin, in vivo
as well as in vitro.

Aubrey de Grey




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