Carnosine and lipofuscin
JohnDoe999 25 Jul 2014
Hi
I've read two books about carnosine, and I have incorporated it in my supplement regime.
Both books give a lot of information about the use and benefits of L-carnosine, but neither mentions anything about Lipofuscin.
I've been reading a couple of articles about L-carnosine and Lipofuscin, and these articles recommend that Lipofuscin due to Carnosine usage is removed by taking either ALC or DMAE daily.
I wonder why this is not mentioned in any of the books? Is it because this is more recent knowledge, or is the necessity of Lipofuscin removal caused by L-carnosine disputed?
Kevnzworld 25 Jul 2014
The only supplements that I've read about that even might reduce lipofuscin buildup are :
Creatine
DMAE
GSE
Centrophenoxine
Edited by Kevnzworld, 25 July 2014 - 02:00 PM.
gt35r 25 Jul 2014
what is GSE? grape seed extract? DMAE does not do anything against lipofuscin.
niner 25 Jul 2014
The whole idea of carnosine causing the formation of lipofuscin was, as far as I can tell, nothing more than a speculation in a paper by Alan Hipkiss. One of the hallmarks of molecular damage to a protein (due to oxidation or glycation) is the formation of inappropriate carbonyls. Carnosine is thought to react with these protein carbonyls, forming "carnosinylated" proteins, which marks them for elimination in some way. The most probable fate of such proteins would be proteolysis leading to soluble products. In order to form lipofuscin, the protein or some part of it would need to be rendered indigestible by proteolytic enzymes. Proteolytic enzymes (proteases) sever the peptide chain at the site of specific residues, for example, trypsin cleaves at lys or arg sites. This has the effect of cutting a protein up into a number of smaller peptides. These shorter peptides are cleaved by other peptidases, and are ultimately broken down into individual amino acids which can be recycled. I think it's unlikely that a small number of carnosine tags would completely prevent proteolysis, and once the protein begins to unravel, it becomes highly exposed to protease attack. Thus the only way I can see for the formation of lipofuscin is that a protein would have to be so badly oxidized that carnosine would label it to such an extent that it would be prevented from any proteolysis, and frankly such a messed up protein should have been eliminated long ago by normal housekeeping. The only other way I can see would be if a short carnosinylated peptide were itself to be the problem. Given the water solubility of peptides, this seems fairly unlikely. Dr. Hipkiss offers circumstantial evidence for the carnosine-lipofuscin hypothesis, in that the most lipofuscin is found in muscle, nerve and brain, tissues that are high in carnosine. However, those also happen to be the most long-lived cells, and short-lived cells are replaced before they accumulate much lipofuscin, so I don't think that is evidence at all. In the linked paper, Hipkiss presents rationale and evidence that carnosinylated proteins are degraded via the proteasome, perhaps even more effectively than oxidized proteins without carnosine, so I think he was just trying to cover all the possible fates of carnosinylated protein when he came up with the lipofuscin idea.
It seems to me that carnosine-induced lipofuscin formation is not likely on the basis of the physical properties of proteins and peptides, and that there isn't any observational evidence for it. If someone has run the experiment where animals are fed carnosine and lipofuscin is analyzed versus controls, that would really sort it out. As far as I'm aware, at this point it's a speculation that doesn't appear very likely to be the case.
Kevnzworld 25 Jul 2014
Yeswhat is GSE? grape seed extract? DMAE does not do anything against lipofuscin.
Re:DMAE
" Administration in the drinking water of 10 mM dimethylaminoethanol to the C3H/HeN mice or 15 mM to the C3H/HeJ(+) mice did not result in significant differences between treated and untreated groups in average survival. No changes in age-related organ structure or morphology were observed with dimethylaminoethanol treatment, except for an apparent decrease in the amount of lipofuscin in the liver judged in histological sections"
http://www.sciencedi...047637488900681
gt35r 25 Jul 2014
Yeswhat is GSE? grape seed extract? DMAE does not do anything against lipofuscin.
Re:DMAE
" Administration in the drinking water of 10 mM dimethylaminoethanol to the C3H/HeN mice or 15 mM to the C3H/HeJ(+) mice did not result in significant differences between treated and untreated groups in average survival. No changes in age-related organ structure or morphology were observed with dimethylaminoethanol treatment, except for an apparent decrease in the amount of lipofuscin in the liver judged in histological sections"
http://www.sciencedi...047637488900681
That study is from 1988 and I do not believe it was been reproduced. There was a thread not too long ago that discussed DMAE and some people mentioned that it was not lipofuscin was not inhibited; in fact i believe it was found that the original studied mistakes lipofuscin for something else.
8bitmore 28 Jul 2014
I reckon Piracetam is actually a pretty good bet as a inhibitor of lipofuscin formation: ( https://www.ncbi.nlm.../pubmed/1755517 )
Then again people may vary a bit from the alcoholic rats used in that particular study...
This particular study, ( https://www.ncbi.nlm.../pubmed/2392876 ), may also offer insights on Piracetam vs lipofuscin accumulation but I'm not sure abstract actually contains sufficient information from study, think odd German - English translation may be to blame.