> I have been doing some reading on the internet about lipofuscin.
> Does anyone know if AGEs and lipofuscin are related to each other?
> could an AGE breaker like ALT-711
> break apart and eliminate lipofuscin from the human body?
Lipofuscin hasn't been discussed here for a long time, and it may be
much more important to aging than has traditionally been thought, so
I'll do a bit more than answer your questions.
The definition you quote is adequate (except that the pigmentation
of age spots/liver spots is not normally classed as lipofuscin,
and I doubt that it's chemically similar), but it omits the cell
types which accumulate the highest levels of lipofuscin, namely the
pigmented epithelium of the retina. There is a consensus that the
levels reached in those cells does indeed interfere with cellular
metabolism, leading to blindness from macular degeneration. The
reason these cells suffer so severely is that they are responsible
for destroying the worn-out light-sensitive material in the other
cells in the retina, and that wearing-out happens at a phenomenal
rate: a given unit of photoreceptor lasts only a week or so.
The effect in other cells, however, is in great doubt: most people
reckon that the accumulation of lipofuscin is completely harmless
at the levels seen elsewhere, even by very old age. Thus, it's the
usual situation -- a completely uncontroversial "theory of eventual
aging" which by no means translates into a theory of actual aging.
However, a few years ago Ulf Brunk suggested (Mutat Res 275:395-403)
a way in which a quite low level of lipofuscin may impose stress on
its host cells: in essence, by "distracting" the cellular recycling
machinery, wearing out the hydrolytic enzymes that constantly (and
vitally) break down old proteins, old mitochondria, old everything
into their biologically elementary constituents (such as free amino
acids) for re-use to make new cellular components. This is still a
viable hypothesis; the cells (excluding the retina) which accumulate
the most lipofuscin are postmitotic ones, which as you know are the
ones that show the greatest deterioration with aging, and moreover
the postmitotic cells that accumulate most are the ones that suffer
most (eg motor neurons lose functionality much more badly than muscle
fibres, as shown by cross-age transplantations (see eg Carlson et al,
Am J Physiol 256:C1262-6)). The only strong evidence against it is
that vitamin E supplementation has been shown to slow accumulation
of lipofuscin quite substantially in mice, but not to increase their
maximum lifespan (Blackett and Hall, Age Ageing 10:191-5); that is
potentially rather persuasive, but it needs to be repeated more
exhaustively (on a larger scale, studying more cell types, etc).
So to your questions. The cross-linking in lipofuscin is generally
described as due to oxidation reactions, but AGE-like links may very
well also be present. If so, then an AGE breaker like ALT-711 may
break it apart somewhat; moreover, there's nothing to say that an
AGE breaker may not also break apart some types of oxidative cross-
links. There are pretty good in vitro assays for this: it's easy to
make lipofuscin accumulate really fast in culture, and to measure
whether the introduction of a given chemical retards or reverses
that accumulation. One chemical, centrophenoxine, has long been
touted to have this effect (Nandy and Bourne, Nature 210:313-4),
but more recent work is less encouraging, finding some retardation
but no definite reversal (though I again feel that we need more data
before we can reach solid conclusions). I would be very surprised
if Alteon aren't doing such experiments.
Aubrey de Grey