Carnosine's effects on proteolysis:
snip...
Timely proteolysis removes damaged proteins before they do significant
harm, and removes undamaged proteins before they become damaged or
disruptive. For example, if oxidized proteins are not broken down, they
tend to cross-link and aggregate (as, for example, in cataracts or senile
plaques). Rapid effective proteolysis is therefore an anti-aging mechanism
(Grune T et al., 1997).
The main proteolytic enzyme complex is called the proteasome. It removes
proteins that have been tagged for degradation by a peptide called
ubiquitin. Through its role in protein disposal, the proteasome-ubiquitin
pathway helps regulate many basic cellular processes including the cell
cycle and cell division, cell differentiation, cellular signaling,
cellular metabolism and DNA repair (Ciechanover A, 1998). Thus a
malfunctioning proteasomal system has far-reaching consequences.
As cells age, after many cell divisions, proteasome activity declines
(Sitte N et al., 2000; Merker K et al., 2000). At the same time, more and
more proteins undergo damage through a process called carbonylation. Thus
the proteolytic system becomes increasingly inadequate to deal with the
increasing numbers of abnormal or unneeded proteins, which can
irreversibly form cross-links and turn cellular processes awry.
New research shows that when the population of carbonylated proteins
permanently increases—as in aging—proteasome activity is depressed
(Petropoulos I et al., 2000; Keller JN et al., 2000; Burcham PC et al.,
1997). A vicious circle develops of age-related decline in proteasomal
activity, age-related increase in protein carbonylation and further
inhibition of the proteasome. The life cycles of proteins become blocked,
and the normal turnover of protein declines.
Is there a way to block this vicious circle? The body contains a dipeptide
called carnosine that both protects proteins from carbonylation and helps
reverse proteasomal decline. As in the aging body, proteolysis declines in
cultured cells as they approach senescence. Australian scientists showed
that carnosine enhances intracellular proteolytic activity in human
connective tissue cells (Hipkiss AR et al., 1995). Carnosine enhanced
proteolysis the most in old cells, and to a lesser extent in “middle aged”
cells, compensating for age-related proteolytic decline (for details see
“Carnosine—Nature's pluripotent life extension agent” from this issue).
""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""
Does dht do something to serine proteases to disrupt damaged cell
proteins? Enuff damaged cell proteins = shutdown(senescence)
: J Invest Dermatol 1999 Sep;113(3):308-13 Related Articles, Books,
LinkOut
The mRNA for protease nexin-1 is expressed in human dermal papilla cells
and its level is affected by androgen.
Sonoda T, Asada Y, Kurata S, Takayasu S.
Department of Dermatology, Oita Medical University, Hasama, Japan.
son...@oita-med.ac.jp
Protease nexin-1, an inhibitor of serine proteases, plays important parts
in the regulation of the growth, differentiation, and death of cells by
modulating proteolytic activity. The mRNA for protease nexin-1 accumulates
in rat dermal papilla cells in a hair cycle-dependent fashion and its
levels are well correlated with the ability of dermal papilla cells to
support hair growth. In an attempt to characterize the potential role of
protease nexin-1 as a modulator of hair growth in humans, we investigated
the steady-state level of protease nexin-1 mRNA in cultured human dermal
papilla cells using a semiquantitative technique that involved reverse
transcription and polymerase chain reaction, as well as the localization
of this mRNA in vivo using dissected hair follicles. Protease nexin-1 mRNA
was expressed in all dermal papilla cells examined, and it was also
identified in the lower part of the connective tissue sheath. Moreover, we
found that levels of protease nexin-1 mRNA were depressed by
dihydrotestosterone, the most potent androgen, in cultured dermal papilla
cells obtained from balding scalp. Our results suggest that protease
nexin-1 might be a key molecule in the control of hair growth in humans
and, moreover, that the androgen-mediated downregulation of the synthesis
of protease nexin-1 might be associated with the progression of
male-pattern baldness.
PMID: 10469326 [PubMed - indexed for MEDLINE]
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Further,from page 2:
http://www.lef.org/magazine/mag2001/jan2001_report_carnosine2_2.html
snip...
Proteolysis of connective tissue is a normal part of skin cell development
and wound healing. Proteolytic enzymes and their inhibitors sculpt
structural proteins and break them down at the appropriate times.
Unfortunately, as aging skin cells senesce and *increase their proteolytic
activity*, the proteasome (the main enzyme complex for protein
degradation) enters an age-related decline. The balance between protein
creation and destruction is again upset, compromising the integrity and
regeneration of skin tissue.
Thanks.
"mike" <emka...@dodgenet.com> wrote in message
news:9u5148$vpb$1...@ins21.netins.net...
> >permanently increases-as in aging-proteasome activity is depressed
> >(Petropoulos I et al., 2000; Keller JN et al., 2000; Burcham PC et al.,
> >1997). A vicious circle develops of age-related decline in proteasomal
> >activity, age-related increase in protein carbonylation and further
> >inhibition of the proteasome. The life cycles of proteins become blocked,
> >and the normal turnover of protein declines.
> >
> >Is there a way to block this vicious circle? The body contains a
dipeptide
> >called carnosine that both protects proteins from carbonylation and helps
> >reverse proteasomal decline. As in the aging body, proteolysis declines
in
> >cultured cells as they approach senescence. Australian scientists showed
> >that carnosine enhances intracellular proteolytic activity in human
> >connective tissue cells (Hipkiss AR et al., 1995). Carnosine enhanced
> >proteolysis the most in old cells, and to a lesser extent in "middle
aged"
> >cells, compensating for age-related proteolytic decline (for details see
> >"Carnosine-Nature's pluripotent life extension agent" from this issue).
Has anyone considered ALT-711 as a topical?
I would try it but where do you find it?
Final answer:I'm really not sure.I'm only trying to link similar things
together.Two adjacent puzzles pieces in a 3-d puzzle.
Final note:Back in the mid 80's I got this call from a Canadian
doctor.He claimed to have solved balding.His explanation I dont agree
with but perhaps now I think was he talking about proteolytic enzymes.
He said to me that there was a membrane on your scalp which prevented
hair growth.(mid 80's remember).I knew better than that and laughed,
maybe outloud to his explanation.But he said he had 2 enzymes which
he applied topically to dissolve this membrane.I dont know why but
bromelain and papain came to mind.They both are proteolytic enzmes and
can be used for debridement.Never tried the treatment.
Maybe just maybe he was correct? Caveat:there is an otc hair remover
containing papain.I have tried it on the back of my neck and doesnt
work.
You see, you must never totally write off anbody's new theories or we may
miss the solution, but of course there are loads of snake-oil salesmen out
there and one must be wary.
"mike" <emka...@dodgenet.com> wrote in message
news:9u7971$92l$4...@ins21.netins.net...
Dont know.
Was the membrane he was talking about
>the galea?
Probably he thought it was.IMO it is something similar to the dermal
striae talked about in the Deanol patent.Glucocorticoids cause this too.
Dr.Pickart has something on his website about dermal aging and
subcutaneous fatloss and balding,prolly is very related.
If so isn't it internal? I do recall there was a bald guy in the
>Zinc Oxide forum in www.hairsite.com who had a facial peel done and I guess
>the person that did it didn't really know where his face ended and his
>hairline began and afterwards he noticed hairs growing in the hair zone
>parts that were peeled. The hairs later went away after some weeks - the
>cause of MPB, whatever that may be, was still in full flight.
There's alot we dont know.There's alot more I dont know.Humbleness(realize
you dont know it all then take it from there) and flexibility(drop a
theory in a second no matter how much time you have in it if so called
for) are the keys to successful researching.Avoid bias(as if)
and dont fall in love with your own theories,they'll break your heart.
However this
>example seems to illustrate that there is definitely something stifling the
>follicle and it can be gotten rid of AND the follicle does not die as some
>theorists purport. The question is how to get ris of this stifling? Chemical
>peels obviously seem promising, perhaps proteolytic enzymes, perhaps
>something radically different? Do you have any further ideas Mike, or
>anybody else?
Nope, fresh out.