33 replies to this topic

[balance]

I'm wondering if someone can give me a list of nutrients that prevent/help against lipofuscin.

I'm aware of the following:

Acetyl-l-carnitine
Lipoic acid
DMAE (some indicate only Centrophenoxine helps against lipofuscin, whilst others state DMAE does as well)

Since there is confusion on DMAE I'm wondering about incorporating other possible nutrients. I take high dose carnosine for preventing glycation and lipofuscin seems to be the only gap in carnosine's protection.


Any help is appreciated.

[kclo4x]

I'm wondering if someone can give me a list of nutrients that prevent/help against lipofuscin.

I'm aware of the following:

Acetyl-l-carnitine
Lipoic acid
DMAE (some indicate only Centrophenoxine helps against lipofuscin, whilst others state DMAE does as well)

Since there is confusion on DMAE I'm wondering about incorporating other possible nutrients. I take high dose carnosine for preventing glycation and lipofuscin seems to be the only gap in carnosine's protection.


Any help is appreciated.

"Piracetam appears to reduce levels of lipofuscin in the rat brain.^[21] (Lipofuscin accumulation is common symptom of aging and alcoholism)." - wiki

http://www.blackwell...ournalCode=acer

[stephen_b]

I was surprised by the amount of lipofuscin accumulation in the speech areas of the brain in the study "A Microscopic Study of Language-Related Cortex in Autism" (abstract, full text):

In controls, the number of lipofuscin containing cells in full-depth cortical samples increased
in all three brain areas from age 8 to age 56 in area 22 by 770% (p = 0.0015); area 39 by 430%
(p = 0.0001); and from age 8 to age 46 in area 44 by 189% (p = 0.0001).

That doesn't sound good. I've started taking 800 mg of piracetam daily. Anyone know whether lipofuscin accumulation impacts other parts of the body?

StephenB

[balance]

Funny coincidence, u have revived this thread, and 10 minutes before seeing it again, I stumbled upon this link:

http://www.ergo-log....elongevity.html

"When brains – and not only brains – age, the amount of the ‘aging pigment’ lipofuscin in the brain tissue increases. Lipofuscin is therefore a marker for aging. The Germans discovered that the hippocampus of the mice in the creatine group contained less lipofuscin. ".

So that basically answers the question that it's not only in the brain, but also that there's another compound to add to this thread/list, which is creatine, also useful against lipofuscin.

U should also go for the Centrophenoxine.

[luv2increase]

DMAE does not remove lipofuscin. It needs to be combined to the plant hormone PCA which makes centrophenoxine for this to occur.



http://www.ncbi.nlm....ov/sites/entrez

1: Exp Aging Res. 1978 Apr;4(2):133-9.Links
Effects of PCA and DMAE on the namatode Caenorhabditis briggsae.
Zuckerman BM, Barrett KA.

Concentration of 6.8 mM DMAE did not retard age pigment accumulation in Caenorhabditis briggsae. However, when the nematodes were exposed to 6.8 mM PCA + 6.8 mM DMAE combined, the accumulation of age pigment was significantly retarded. A combination of 3.4 mM DMAE + 3.4 mM PCA had no effect on age pigment. It is concluded from this study that PCA and DMAE act in concert to produce the observed effect on age pigment. In respect to this parameter neither molecule was effective alone. The results indicate that the effect of centrophenoxine on age pigment might be enhanced by retarding the hydrolysis of centrophenoxine. The accumulation of electron dense aggregates, thought to be aggregates of cross-linked molecules, was reduced by 6.8 PCA + 6.8 DMAE. It is suggested that centrophenoxine be tested for its ability to remove random, unwanted cross-linkages in higher animals.

PMID: 348477 [PubMed - indexed for MEDLINE]

[caston]

So what does PCA stand for?

[Gerald W. Gaston]

So what does PCA stand for?

Perchloric Acid

[caston]

http://en.wikipedia....Perchloric_acid

Hardly looks like a safe supplement...

[Gerald W. Gaston]

http://en.wikipedia....Perchloric_acid

Hardly looks like a safe supplement...

Well does "pyrrolidone carboxylic acid" look better? J/K

No seriously Caston... I apologize... I should have looked at what you were discussing closer as neither are what you are really after. In the context of Centrophenoxine it is actually Parachlorophenoxyacetate (also often referred to as pCPA)

Edited by frankbuzin, 07 March 2009 - 10:25 AM.

[caston]

http://en.wikipedia....Perchloric_acid

Hardly looks like a safe supplement...

Well does "pyrrolidone carboxylic acid" look better? J/K

No seriously Caston... I apologize... I should have looked at what you were discussing closer as neither are what you are really after. In the context of Centrophenoxine it is actually Parachlorophenoxyacetate (also often referred to as pCPA)

Thank you

[krillin]

According to Aubrey's book, centrophenoxine doesn't work either. It seems that people were mistakenly calling ceroid lipofuscin. Here are some of what he cites.

Ann N Y Acad Sci. 2002 Apr;959:57-65.
Pigments in aging: an overview.
Porta EA.
Department of Pathology, University of Hawaii, School of Medicine, Honolulu, Hawaii 96822, USA. portae@jabsom.biomed.hawaii.edu

Although during the normal aging process there are numerous pigmentary changes, the best recognized are those of melanin and lipofuscin. Melanin may increase (e.g., age spots, senile lentigo, or melanosis coli) or decrease (e.g., graying of hair or ocular melanin) with age, while lipofuscin (also called age pigment) always increases with age. In fact, the time-dependent accumulation of lipofuscin in lysosomes of postmitotic cells and some stable cells is the most consistent and phylogenetically constant morphologic change of aging. This pigment displays a typical autofluorescence (Ex: approximately 440; Em: approximately 600 nm), sudanophilia, argyrophilia, PAS positiveness, and acid fastness. Advances on its biogenesis, composition, evolution, and lysosomal degradation have been hampered by the persistent confusion between lipofuscin and the large family of ceroid pigments found in a variety of pathological conditions, as evidenced by the frequent use of the hybrid term lipofuscin/ceroid by investigators mainly working with in vitro systems of disputable relevance to in vivo lipofuscinogenesis. While lipofuscin and ceroid pigments may share some of their physicochemical properties at one moment or another in their evolutions, these pigments have different tissue distribution, rates of accumulation, origin of their precursors, and lectin binding affinities. Although it is widely believed that lipofuscin is a marker of oxidative stress, and that it can be, therefore, modified by antioxidants and prooxidants, these assumptions are mainly based on in vitro experiments and are not generally supported by in vivo studies. Another common misconception is the belief that lipofuscin can be extracted from tissues by lipid solvents and measured spectrofluorometrically. These and other disturbing problems are reviewed and discussed in this presentation.

PMID: 11976186

Exp Gerontol. 1985;20(6):333-40.
Quantitative studies of the effects of aging, meclofenoxate, and dihydroergotoxine on intraneuronal lipopigment accumulation in the rat.
Dowson JH.

Intraneuronal lipopigment accumulation is associated with ageing and certain diseases, and there are many claims that this can be influenced by drugs, particularly meclofenoxate (centrophenoxine). The various unsubstantiated or conflicting reports of the effects of this drug in animal studies indicate the need for methods for the demonstration of lipopigment accumulation in adequately defined, easily-identified, and relatively homogeneous neuronal populations; this study has validated two such methods by demonstrating significant differences between groups of rats at different ages in respect of measured lipopigment autofluorescence intensity from the most heavily pigmented regions of a subpopulation of Purkinje cells, and of the area overlying intraneuronal lipopigment in a region of the hippocampus. These methods were then used to investigate the effects of daily (5 days per week) intraperitoneal injections of meclofenoxate or dihydroergotoxine, over a period of 12 weeks, before sacrifice at 13.5 months. No significant effects of meclofenoxate were detected, but dihydroergotoxine administration was associated with a significant increase in mean area overlying intraneuronal lipopigment in the CA3a region of the hippocampus. The results do not confirm that meclofenoxate can induce a reduction in intraneuronal lipopigment, but suggest that chronic dihydroergotoxine administration was associated with an increase in intraneuronal volume of lipopigment in the cell bodies of CA3a hippocampal neurones.

PMID: 3938737

Neurobiol Aging. 1986 Mar-Apr;7(2):107-13.
Lipofuscin in retinal pigment epithelium of rhesus monkey: lack of diminution with centrophenoxine treatment.
Andrews LD, Brizzee KR.

An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sections from the perifovea of ten rhesus monkeys, all approximately 20 years of age. Four of the animals received 80 mg/kg Centrophenoxine (IM injection) daily for 12 weeks. No significant difference between the treated and control groups could be demonstrated statistically (Mann-Whitney U-test) either in the fraction of RPE cell cytoplasm occupied by lipofuscin granules or in the average size of the granules.

PMID: 3083280

J Gerontol. 1983 Sep;38(5):525-31.
Lipofuscin response to the "aging-reversal" drug centrophenoxine in rat retinal pigment epithelium and frontal cortex.
Katz ML, Robison WG Jr.

The effects of centrophenoxine on the lipofuscin contents of the retinal pigment epithelium (RPE) and frontal cortex of the brain were examined in senescent female Fischer rats. Rats (106 weeks old) were injected daily for 11 weeks with centrophenoxine (80 to 120 mg/kg body weight) or saline, and then sacrificed along with untreated 28- and 46-week-old controls. The number of lipofuscin granules seen in the RPE by light microscopy increased by 70% between 28 and 117 weeks of age in control animals. There was a concomitant age-related increase in lipofuscin specific fluorescence in the RPE. Centrophenoxine treatment neither reduced the amount of lipofuscin, nor altered the ultrastructural appearance of lipofuscin granules in the RPE. Between 28 and 117 weeks of age, there was an almost nine-fold increase in the lipofuscin content of the frontal cortex of control animals; centrophenoxine treatment failed to reverse this pigment accumulation.

PMID: 6411800

[balance]

Very interesting krillin. But does he mention a method that we CAN use?

First debunking MK-4 and now this. Sure saves me a couple of bucks, for that I thank you .

[waldemar]

F**k. Ok, no more Centrophenoxine for me... Or is there something else that it's good for (except as a Choline source)?

[krillin]

Very interesting krillin. But does he mention a method that we CAN use?

Nope. That's why we need LysoSENS.

[waldemar]

Ok, what about ALCAR?

[luv2increase]

I wouldn't take in those studies posted for centrophenoxine's inability of lipofuscin removal and prevention for granted. There are more studies which show it does a great job at doing so. It is more so a majority pull if you know what I mean.

[krillin]

I wouldn't take in those studies posted for centrophenoxine's inability of lipofuscin removal and prevention for granted. There are more studies which show it does a great job at doing so. It is more so a majority pull if you know what I mean.

As I noted, the authors of the positive studies were actually studying something else that they erroneously called lipofuscin.

[luv2increase]

I wouldn't take in those studies posted for centrophenoxine's inability of lipofuscin removal and prevention for granted. There are more studies which show it does a great job at doing so. It is more so a majority pull if you know what I mean.

As I noted, the authors of the positive studies were actually studying something else that they erroneously called lipofuscin.

Hmmm.. You quoted According to Aubrey's book, centrophenoxine doesn't work either. It seems that people were mistakenly calling ceroid lipofuscin. Here are some of what he cites.. This could be taken as two different meanings. 1) We were wrong because we thought centrophenoxine was removing was lipofuscin, but it indeed was ceroid instead, or 2) The studies you posted were referring to the erroneous lipofuscin and not the real deal hence they don't have any meaning because they show centrophenoxine isn't effective against ceroid rather than lipofuscin.


I think you need to be a little more specific. It should have been a warning sign to you krillin that you were being misunderstood when waldemar posted

F**k. Ok, no more Centrophenoxine for me... Or is there something else that it's good for (except as a Choline source)?

.... I guess it needed more than one person for you to understand you were being misunderstood. Oh well, at least we know that centrophenoxine is all good now for the REAL lipofuscin.

Cheers

[VespeneGas]

Not to speak for Krillin, but I read his comment as unambiguously (1), that centrophenoxine reduces a pigment other than lipofuscin. I'm not sure how waldemar's comment is evidence of confusion, only that centrophenoxine doesn't do what it has historically purported to do, and therefore isn't worth the price (if it's just a fancy choline source).

[balance]

It seemed pretty clear to me that he showed that it's not worth taking centrophenoxine if for the purpose of lowering lipofuscin content in the brain. That was the only reason I was taking it. Indeed, it seems that it's purpose is more an expensive DMAE/choline supplement. DMAE wasn't a good source for choline as I remember reading something that it competed with other choline sources in the brain (don't quote me), and therefore phosphatidylcholine, alpha-gpc, are the better forms to stick with. Choline bitartrate is a no go, and I'm still wondering whether PPC is actually equivalent to alpha-gpc:

http://www.lef.org/V.../HepatoPro.html

http://www.lef.org/m...r00-report.html

http://www.lef.org/m...2005_aas_01.htm

[waldemar]

There are more studies which show it does a great job at doing so. It is more so a majority pull if you know what I mean.

Scientific discoveries etc. are not democratic. The truth is not decided by popular vote. The "majority pull" only works (reasonably well) in politics.

Having said that, now I'm really confused. Do we have any more information? Any pretty pictures of rat brains where Centrophenoxine obviously helps or doesn't help? :-)

[luv2increase]

Having said that, now I'm really confused. Do we have any more information? Any pretty pictures of rat brains where Centrophenoxine obviously helps or doesn't help? :-)

Don't listen to that Aubrey guy. Last I heard of him is that he doesn't even believe in supplements at all. If that doesn't tell you anything than I don't know what will.


Simply go to pubmed and type in "centrophenoxine + lipofuscin"...

[krillin]

Don't listen to that Aubrey guy. Last I heard of him is that he doesn't even believe in supplements at all. If that doesn't tell you anything than I don't know what will.

That's because he's working on ending aging, not the amateurish delaying that our regimens are attempting. Even CR doesn't meet his standards. (I actually consider him a supplement optimist if Geronova correctly quoted him as saying RALA would only get us 10-15 more years max. It's in the middle of a PowerPoint on their site.)

[luv2increase]

Don't listen to that Aubrey guy. Last I heard of him is that he doesn't even believe in supplements at all. If that doesn't tell you anything than I don't know what will.

That's because he's working on ending aging, not the amateurish delaying that our regimens are attempting. Even CR doesn't meet his standards. (I actually consider him a supplement optimist if Geronova correctly quoted him as saying RALA would only get us 10-15 more years max. It's in the middle of a PowerPoint on their site.)

Any average joe can see that supplementation is a good starting point. You may or may not know that there are many areas that scientists are targeting to shorten and/or halt aging like advanced glycation end-products etc... If Aubrey had the slightest of intelligence, he would not rule out supplements in the least. Simply put, he doesn't stand for the use of supplements and because of that, I do not trust his input. He is a quack as far as I'm concerned.

[krillin]

Don't listen to that Aubrey guy. Last I heard of him is that he doesn't even believe in supplements at all. If that doesn't tell you anything than I don't know what will.

That's because he's working on ending aging, not the amateurish delaying that our regimens are attempting. Even CR doesn't meet his standards. (I actually consider him a supplement optimist if Geronova correctly quoted him as saying RALA would only get us 10-15 more years max. It's in the middle of a PowerPoint on their site.)

Any average joe can see that supplementation is a good starting point. You may or may not know that there are many areas that scientists are targeting to shorten and/or halt aging like advanced glycation end-products etc... If Aubrey had the slightest of intelligence, he would not rule out supplements in the least. Simply put, he doesn't stand for the use of supplements and because of that, I do not trust his input. He is a quack as far as I'm concerned.

Could you supply the statement(s) of his that offended you so? He seems quite reasonable in this interview.

Nutritional supplements are certainly useful. I focus on more futuristic technologies mainly because that's where the effort is most needed - there are lots of experts on supplements. My view of supplements is in line with what the famous biochemist Bruce Ames says: a standard multivitamin a day is a risk-free insurance policy against dietary deficiency in any of the dozens of essential micronutrients, so everyone should take one, especially if you're over 40.

[Logan]

What about piracetam? It was mentioned above. I'm going to try this for creativity and cognition, and if I like it and continue to take it, I may be cleaning up the lipofuscin and killing two birds with one stone.

[katzenjammer]

There are quite a few studies on pubmed like this below. For some reason, centro makes me feel like sh*t - too wired and anxious. Anyone understand the mechanism of how/why centro may decrease lipofuscin - perhaps there's another way to achieve the same thing?

Why not take Alpha-GPC for this purpose?

1: Neurobiol Aging. 1993 Jul-Aug;14(4):319-30.Links
Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine.

Sharma D, Maurya AK, Singh R.
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age-related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age-associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration.

[adamh]

I would not take one study too seriously no matter what the conclusions. If we don't go with the majority then what do we do with conflicting results? It's rare to find total consensus on any subject. I would not toss centro out the window just based on one or even two studies when there have been many others that showed a lot of benefit. For what it's worth, I get a little wired on centro too and have to keep the dose low. No problems with piracetam though.

[krillin]

Anyone understand the mechanism of how/why centro may decrease lipofuscin - perhaps there's another way to achieve the same thing?

People who understand lipofuscin know that no supplement has been shown to stop it from accumulating. Just because an author uses the word lipofuscin in his paper, you cannot assume that he was actually measuring lipofuscin. The only non-delusional method of fighting lipofuscin is to donate to LysoSENS.

[Kevnzworld]

I just read this article . Creatine inhibits sarcopenia and according to this article, lipofuscin too
Recently, creatine has been found to significantly lower the accumulation of a recognized marker of aging called lipofuscin in the brains of aging mice.1 As a result, creatine-fed mice lived an average of 9% longer than control animals thats equivalent to more than seven years for an average human!1

http://www.lef.org/m...ch&key=creatine

Thoughts ?