331 replies to this topic

[Turnbuckle]

I personally take NOW foods "EGCG green tea extract" for my stem cell combo
It is said to contain "min. 98% Total Polyphenols, 80% Total Catechins, and 50% EGCg (Epigallocatechin Gallate) (200 mg)"

Good recommendation. I already take D & carnosine, so with the other things that ought to work great.

[niner]

Turnbuckle, I dont know it you are familiar with that 2006 study, but it seems that the better herbs/nutrients combination for stem cell proliferation is
carnosine + vit D3 + green tea polyphenols (but not pure ECGC) + blueberry

Here is the pubmed abstract http://www.ncbi.nlm....pubmed/16522169
the full study paper http://www.nutrastem...oliferation.pdf

This work was done in cell culture, where isolated cells were continuously bathed (for 72 hours) in these substances at concentrations that may be impossible to reach in vivo. Also, the authors all have conflicts of interest given at the end of the full text. I take (or have taken) all of these, so I'd be interested in knowing if there's any in vivo evidence that they enhance stem cell proliferation. GTE and blueberry are useful for various reasons; I'm less sure about carnosine, given the high level of ravenous carnosinases in humans. D3 may or may not be good, depending on your circumstances.

At any rate, I don't think that the cell culture results are very likely to be applicable to humans.

[Fred_CALICO]

Turnbuckle, I dont know it you are familiar with that 2006 study, but it seems that the better herbs/nutrients combination for stem cell proliferation is
carnosine + vit D3 + green tea polyphenols (but not pure ECGC) + blueberry

Here is the pubmed abstract http://www.ncbi.nlm....pubmed/16522169
the full study paper http://www.nutrastem...oliferation.pdf

This work was done in cell culture, where isolated cells were continuously bathed (for 72 hours) in these substances at concentrations that may be impossible to reach in vivo. Also, the authors all have conflicts of interest given at the end of the full text. I take (or have taken) all of these, so I'd be interested in knowing if there's any in vivo evidence that they enhance stem cell proliferation. GTE and blueberry are useful for various reasons; I'm less sure about carnosine, given the high level of ravenous carnosinases in humans. D3 may or may not be good, depending on your circumstances.

At any rate, I don't think that the cell culture results are very likely to be applicable to humans.

For Niner : "D3 may or may not be good, depending on your circumstances." You could tell me more.

I also wanted to tell you that in europe, a leader in the sale of product longevity announces two new features:
SAIKOSAPONIN A (trade name):
Saikosaponin A 4 mg


AND

STEM CELLS ACTIVATOR (trade name):
Extract of Polygonum multiflorum 12:1 800 mg Fucoidan (from 375 mg Laminaria japonica extract standardised to 80 % Fucoidan) 300 mg Extrait of Bog Blueberry (Vaccinium uliginosum) standardised to 25 % anthocyanidins 250 mg Beta 1,3/1,6 glucans (from 215 mg oat extract standardised to 70 % de beta 1,3/1,6 glucans) 150 mg Green tea extract standardised to 95% polyphenols of which 75% are catechins including 45% EGCG 150 mg L-carnosine 50 mg Astragaloside IV (from 21 mg extract of Astragalus membranaceous standardised to 98 % astragaloside IV) 20 mg Vitamin D3 400 UI
Other ingredients : microcrystalline cellulose, magnesium stearate (E572), silicon dioxide (E551).

For information description / claim:

1/ SAIKOSAPONIN A
Researchers are constantly and actively engaged in the quest to hold off the ravages of aging and extend human lifespan. The latest advances in genetics are generating significant new optimism.

¤ Experiments have shown that the lifespan of mice could be extended by over 45%! Since the genes responsible are present and have similar roles in both mice and humans, this suggests that humans might be able to live, under certain conditions, to the age of almost 125.

¤ Top geneticists (such as Aubrey de Grey, for whom this represents a major breakthrough which scientists have been trying to achieve for years) and cancer experts (such as Maria Blasco of the National Cancer Research Centre in Spain) have reached the same conclusions on the identification and use of these genes.

¤ The telomerase gene boosts the immune system and in particular, lengthens the shortest telomeres - the tips of chromosomes. It responds exceptionally well to astragaloside IV and cycloastragenol.

¤ The P53 gene (or ‘tumour suppressor’) is activated more specifically by resveratrol and its derivatives.

¤ The P16 gene, also a ‘tumour suppressor gene’, completes the picture by controlling anarchic cell mitosis. Recently, it has been possible to use P16 gene concentration, which increases in human tissue with age, in blood tests as a biomarker for cell aging. A new plant substance - saikosaponin A – has been specifically selected and isolated in order to activate this P16 gene.

¤ Bupleurum falcatum, or Buplevre, belongs to the Apiacaeae plant family and is used in traditional Chinese and Japanese medicine. It is widely considered to be a cell detoxifier that helps fight chronic infection and inflammatory conditions (particularly hepatitis). Bupleurum has recently increased in popularity due to favourable results achieved in cancer treatment. Its active principles are the saikosaponins A, B, C and D. Of these, it is the A form, a triterpenoid glycoside, that activates the tumour-suppressing P16 gene, but it is extremely rare and expensive (you would need to consume 50,000 mg of Bupleurum to obtain the amount of saikosaponin A available in one of our capsules).

¤ A number of studies have confirmed that saikosaponin A destroys cancer cells while leaving normal lymphocytes intact. The most notable of these studies, conducted at the National Cancer Research Centre in Madrid, combined saikosaponin A with astragaloside IV. It showed that treated mice lived significantly longer than controls, however advanced their tumours. Researchers also observed that mice with cancer, whose diet had been supplemented with saikosaponin A only, lived longer than healthy mice. The researchers concluded that: “When P53 and P16 genes were activated in mice, cancer incidence was reduced to practically zero”. This encouraging animal research has already led to the development of human treatments in the oncology departments of a number of Chinese hospitals.

¤ The Spanish scientists concluded that the activation of these three genes – telomerase, P53 and P16 – represented a major contribution to the prevention and regression of tumours by apoptosis (programmed cell death). They added: “We do not think that the mice lived longer because they didn’t have cancer, but because these genes protected them against aging”.

¤ The benefits of saikosoaponin A are enhanced when it is combined, though not simultaneously*, with astragaloside IV or cycloastragenol, which activate the telomerase gene, and with resveratrol and its derivatives, which activate the P53 gene.

Supplementation with saikosaponin A is recommended on a non-continuous or alternating basis, ie, every other week, with the substances mentioned above. Three capsules a week is the dose generally recommended, to be taken every other week. A pack should therefore last for two months. .



2/STEM CELLS ACTIVATOR :
Stem cell therapy represents both a major medical advance and a great hope in the fight against degenerative conditions for which medicine has so far only provided short-lived or temporary solutions.
It is now possible, in some countries, to have injections of adult stem cells extracted from bone marrow, or indeed ‘cultivated’ after extraction from adipose tissue, though more generalised application of this method is still some way off, due to its cost and complexity.

¤ It is this issue that most studies have concentrated on in recent years, and certain researchers have indeed managed - by using nutrients and botanical extracts - to stimulate and increase numbers of adult stem cells in bone marrow.

¤ Researchers are focusing on bone marrow as the source of this regeneration activity, as these cells are renewed on a daily basis, producing new lines of red and white blood cells and platelets. Mature cells are then released into the bloodstream to fulfil their vital, regenerative functions.

¤ Among the nutrients shown to be most active in this area are:

• Extract of Polygonum multiflorum or FO-TI, which when given at the optimal dose of 800mg of a 12:1 extract, is recognised in Chinese medicine as an effective blood tonic, and in particular as a major factor in longevity due to its ability to increase levels of circulating superoxide dismutase (SOD) and monoamine oxidase. Mouse studies conducted in Taiwan show that after daily administration of high-dose Polygonum multiflorum, significant improvements were noted in red blood cells, and in particular, a higher percentage of hematocrit compared with a control group. This research also shows that doses at this level stimulate proliferation of stromal and haematopoietic stem cells in bone marrow.
• Fucoidan is recognised for its immune-stimulant properties and is widely used in Japan to treat cancer. It is extracted from a type of algae, Laminaria japonica, part of the laminaria family. This sulphated polysaccharide boosts the immune system, helping protect the body more effectively against different viruses and in particular, promoting apoptosis (programmed cell death) of cancer cells.
- Like other active algae extracts, fucoidan has demonstrated, at certain concentrations, the ability to stimulate bone marrow stem cells. Studies showed it produced an increase in alkaline phosphatase activity, and at a molecular level, improved the expression of specific genes related to osteogenesis and osteogenic differentiation, thus promoting bone regeneration.
- By directly affecting stem cell mobilisation, fucoidan facilitates more effective repair of damaged tissue, both in cardiovascular health, following a heart attack, and the health of joints and vital organs.
• Astragaloside IV is already known for its telomere-lengthening effects. Research shows this saponin stimulates the immune system in various ways, in particular, by increasing stem cells in the spinal cord and lymphatic tissue and encouraging them to develop into active immune cells.
- Astragaloside IV also supports proliferation of mesenchymal stem cells, pluripotent tissue stem cells that help form skeletal connective tissue such as bone and cartilage.
• Extract of blueberry (Vaccinium uliginosum) can restore certain cell functions that decline over time. It has been shown to increase neurogenesis in the brains of elderly laboratory rats. Researchers experimented with neural tissue transplantation following cell damage caused by neurodegenerative disease or brain injury. As a general rule, transplanted tissue has very little chance of surviving, particularly in older recipients. But when animals were supplemented with blueberry extracts, the growth of the transplantation was more vigorous and cell organisation was comparable to that observed in younger recipients. Blueberry extracts confer their beneficial effects by increasing proliferation of neural stem cells.
• Beta 1,3/1,6 glucan is a polysaccharide extracted from oats. Most research has highlighted its powerful immune-modulatory effects. The latest studies suggest that beta 1,3/1,6 glucan promotes haematopoiesis and boosts proliferation of stem cells, thus facilitating repair of white blood cells in bone marrow.
• L-carnosine improves replicative capacity of myoblast cultures.
- Certains myoblasts, called satellite cells, remain on the periphery of muscle fibres, intervening in its repair when damaged. However, with increasing age comes sarcopaenia (loss of muscle mass) and the satellite cells are no longer able to repair the damage. According to a study on myoblasts, the stem cells responsible for skeletal muscle formation, supplementing with L-carnosine increases their replicative capacity and also reduces the activity of beta-galactosidase.

¤ Epidemiological studies show that a diet rich in colourful fruits and vegetables, and thus polyphenols, can lower the risk of neurodegenerative diseases such as cognitive deficiency, dementia, Parkinson’s or Alzheimer’s disease. Research has demonstrated that certain natural substances can affect adult stem cells, and as a result, increase neurogenesis and improve cognitive ability. Scientists therefore examined a synergistic combination ofextracts of blueberry, green tea, L-carnosine and vitamin D3. When given to rats, this unique combination clearly reduced oxidative stress, and in particular, demonstrated its ability to encourage proliferation of neural stem cells as well as their migration to damaged brain cells (for example, following a stroke).

What improvements can be expected from using Stem Cells Activator?
• an increase in average lifespan and quality of life, as a direct result of enhanced capacity for cell replication ;
• a decrease in the decline in immune function that increases susceptibility to infection, chronic inflammatory attacks and degenerative diseases;
• an improvement in the condition and pain associated with degenerative complaints.
What was only the hope or vision of a few has just become the subject of the Nobel Prize in Medicine 2012 and could tomorrow become a reality …

[niner]

For Niner : "D3 may or may not be good, depending on your circumstances." You could tell me more.

The main thing is that vitamin D has a U-shaped mortality curve like most everything else. (Things that aren't U-shaped will be half U-shaped, though the dimensions of the curve can differ wildly.) Too little D is bad, and too much D is bad, so your supplementation should be guided by occasional blood levels of 25-OH-D3. I'm shooting for 30ng/ml myself, but I have a bad family history for prostate cancer, for which high D levels are a risk factor. Others might want a higher level.

¤ Experiments have shown that the lifespan of mice could be extended by over 45%! Since the genes responsible are present and have similar roles in both mice and humans, this suggests that humans might be able to live, under certain conditions, to the age of almost 125.

¤ Top geneticists (such as Aubrey de Grey, for whom this represents a major breakthrough which scientists have been trying to achieve for years) and cancer experts (such as Maria Blasco of the National Cancer Research Centre in Spain) have reached the same conclusions on the identification and use of these genes.

I think that Aubrey and Dr. Blasco would be displeased to hear that their names are being associated with the claims of this product. I think they would tell people not to get their hopes up on this particular formulation, and I'd have to agree with them.

[Fred_CALICO]

Thank you for your information.

[mpe]

I've been giving C60oo a bit of thought in the last few days, particularly in explaining why younger users haven't experienced the effects we older users have.
The first and most obvious component is its antioxidant effect which is presumably on mitochondria as demonstrated by Turnbuckles remarkable partial recovery of his former athletic ability. Clearly younger users don't benefit because they have largely undamaged mitochondria.
The second but greater effect that younger people don't see i think is largely hormonal. It's well known that as we age our hormone levels decline gradually at first but at an increasing rate as the years progress. The result is thinning and loss of hair, wrinkling, sagging skin, loss of muscle mass, strength and endurance, increased body fat levels, poor sleep, reduction in REM sleep and in the case of women loss of sexual desire, vaginal dryness and menopause.
I propose that C60oo acts on the hypothalamus either by its antioxidant effect or by direct stimulation. The hypothalamus in turns stimulates the production of growth and sex hormones, this explains the observed effects, of stem cell stimulation ( hair growth, hair regimentation arthritic knee regeneration ) skin tightening, increased strength and endurance, increased sleep and dreaming, increased sexual desire,vaginal lubrication and resumption of menses. Once again younger users don't experience these changes as their hormone levels are not sufficiently reduced so that they notice the restoration of hormonal production.
My theory could be tested by blood testing for hypothalamus hormones ( growth hormone releasing hormone etc), ideally with a before and after test, but failing that a blood test looking for elevated ( age adjusted ) hypothalamus hormone levels.

[Kevnzworld]

I've been giving C60oo a bit of thought in the last few days, particularly in explaining why younger users haven't experienced the effects we older users have.
The first and most obvious component is its antioxidant effect which is presumably on mitochondria as demonstrated by Turnbuckles remarkable partial recovery of his former athletic ability. Clearly younger users don't benefit because they have largely undamaged mitochondria.
The second but greater effect that younger people don't see i think is largely hormonal. It's well known that as we age our hormone levels decline gradually at first but at an increasing rate as the years progress. The result is thinning and loss of hair, wrinkling, sagging skin, loss of muscle mass, strength and endurance, increased body fat levels, poor sleep, reduction in REM sleep and in the case of women loss of sexual desire, vaginal dryness and menopause.
I propose that C60oo acts on the hypothalamus either by its antioxidant effect or by direct stimulation. The hypothalamus in turns stimulates the production of growth and sex hormones, this explains the observed effects, of stem cell stimulation ( hair growth, hair regimentation arthritic knee regeneration ) skin tightening, increased strength and endurance, increased sleep and dreaming, increased sexual desire,vaginal lubrication and resumption of menses. Once again younger users don't experience these changes as their hormone levels are not sufficiently reduced so that they notice the restoration of hormonal production.
My theory could be tested by blood testing for hypothalamus hormones ( growth hormone releasing hormone etc), ideally with a before and after test, but failing that a blood test looking for elevated ( age adjusted ) hypothalamus hormone levels.

I dont think that increased hypothalmic hormone output is congruent with Baati's results. Increased IGF-1 and growth hormone is associated with reduced lifespan in mice.
http://classes.biolo...ger_et_al._.pdf
http://www.sciencedi...096637408000889
Quote:
" More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals "

This is why that though I take bioidentical replacement hormones, I've avoided HGH. I also take C60, 1.6 mg daily, biweekly. I am 56 and have not as of date noticed any obvious changes.

[niner]

This hormonal idea is another one to add to the list of hypotheses. The problem I have with it is that so much of what we've seen hasn't been observed with hormone replacement. The hypothesis that I'm really liking these days is the encouragement of (or rescue of failed) stem cell differentiation. Stem cells primarily get their energy from glycolysis, which explains their long-lived nature. When they differentiate, they shift over to oxidative phosphorylation using mitochondria. The mitochondria in stem cells appear immature and non-functional, although they've been shown to have functional ETCs. The mitochondria in stem cells are prevented from functioning by an uncoupling protein called UCP2, which is repressed upon differentiation. There's a lot of mechanistic blanks to be filled in here- essentially this is a hand-wavy relationship between the mitochondrial involvement in stem cell differentiation and the mitochondrial functions that c60-oo is thought to be involved in. At any rate, some kind of stem cell differentiation helping role would explain the effects we've seen that aren't easily explained by an antioxidant mechanism.

[daouda]

Some of the reported effects of C60 remind me of some of the effects that thymosin beta 4 is said to have, and that have been reported by some of the bodybuilding guinea pigs that have been using it. TB4 acts as an actin sequestrant to promote stem cell migration and differentiation. It could be interesting to research the effect of C60-oo on actin. All ive found so far is this http://www.ncbi.nlm....pubmed/22873064 which seems irrelevant but maybe hints that c60-oo might potentially interact with actin in some way.

On an unrrelated note, have you guys seen that study and is this relevant to c6o-oo?
http://www.ncbi.nlm....pubmed/19839607
Our results indicate that C(60)(C(COOH)(2))(2) nanoparticles possess a novel ability of selectively entering oxidation-damaged cerebral endothelial cells rather than normal endothelial cells and then protecting them from apoptosis.

Edited by daouda, 24 December 2012 - 04:00 PM.

[trance]

More theories involving C70 mostly, along with fullerenes in general ...


http://www.ncbi.nlm....pubmed/20138243


These are the first studies examining fullerene trafficking within human MC. It was observed that the C70-TR conjugated fullerenes were taken up through an endocytosis-dependent mechanism and persisted in the MC for up to one week. The intracellular localization was found predominately in the ER and to a lesser degree in mitochondria and lysosomes. No fullerenes were detected in the tryptase-containing secretory granules or in the nucleus at any time-points measured. Taken together, it is clear that MC actively take up fullerenes through an endocytotic pathway where they remain mostly localized to ER and to a lesser extent in lysosomes and mitochondria.

The ER is the site for synthesizing and ensuring proper folding of proteins within a cell and shuttles misfolded proteins through a degradative pathway. Recent evidence suggests this process involves the formation of disulfide bonds that stabilize the folding of nascent proteins resulting in an oxidizing environment and ROS generation (13). In addition to the ER, mitochondria also produce ROS due to the production of ATP following oxidative phosphorylation. Our results using C70-based derivatives are consistent with several publications examining fullerene localization in different cell types in which deposition in different intracellular organelles depends on the moieties added to the carbon cage (2;14–17). For example, C63(COOH)6 or C61(CO2H)2 appear to localize to mitochondria (14;16) while C60 mixtures dispersed in tetrahydrofuran (and not purified from this solvent) localize to lysosomes and nuclei in macrophages (17). Our results are also consistent with previously studies suggesting fullerenes can easily penetrate into a lipid membrane where they induce non-toxic changes in the structural and elastic properties of the lipid bilayer at very high concentrations (18). Taken together, fullerenes as a general class have a varied localization profile within cells; how the fullerene cage is modified determines where the cage localizes in situ. Given that no fullerene formulation has yet been identified for treating a particular disease it is difficult to extrapolate in situ localization results from different fullerene preparations.

The results demonstrating that C70-based fullerenes are endocytosed and localize to ER differentiate from previously published results showing that endocytosed C60-based fullerenes localize to the mitochondria and lysosomes (19;20). The ER accumulation of C70-based fullerenes explains the data shown that pre-incubation of MC with the same fullerenes caused a reduction of FCεRI-mediated calcium release and ROS generation. These findings may help explain fullerenes mechanism of inhibition of FcεRI activated mediator release from MC. In a separate publication (J. Immunology.) we demonstrate that the C70-based derivatives not unlike the one used for the TR conjugation blunts histamine degranulation and cytokine release when MC are pre-challenged with equivalent concentrations and times as described herein. The release of calcium stores and production of ROS occur in these organelles (21); while release of calcium stores is absolutely required for FcεRI-mediator release it is still no clear if increased ROS levels parallel mediator release or is a consequence of FcεRI crosslinking. Calcium stores release from the ER in response to FcεRI crosslinking is controlled by inositol 1,4,5-trisphosphate. Thus, the observation that fullerenes localize to this organelle fits well with our data showing that calcium stores release and ROS production are inhibited when FcεRI-challenged MC are pre-challenged with fullerenes. Current efforts are aimed at determining what ER-associated signaling molecules (if any) are bound to fullerenes which would help explain how these molecules exert their inhibitory activities.

Fullerenes were also consistently found (but to a lesser extent as compared to ER accumulation) in lysosomes. Endocytosis from the plasma membrane can occur by a variety of mechanisms and once uptake occurs the molecules are then routed through lysosomes to various places within cells. We observed lysosomal accumulation of C70-TR predominately at four hour, 96 hour, and one week after washout perhaps indicating the cells shuffling the conjugates from the membrane early and to the membrane for possible excretion at the later times. Indeed, there appears to be a localization of fullerenes in the outer edges of the cell at later times (Figures 4 and 5) possibly indicated that their imminent transport out of the cells.

As mentioned above, the mitochondria is another organelle that is best known for its role in ROS production which is a result of the electrochemical membrane potential (ΔΨm) across the inner mitochondrial membrane (21). We found sporadic localization of the C70-TR in the mitochondria at some of the times examined. Mitochodrial localization has been demonstrated previously either directly or indirectly using other fullerene preparations (14;16;22;23). Given that fullerenes are potent anti-oxidants that can react with ROS it has been speculated that much of their inhibitory capabilities are linked to this radical scavenging ability. However, we show here that fullerenes that are effective anti-inflammatory agents mainly target ER which is also a ROS-producing organelle. It is possible the C70-TR may not reflect the same targeting specificity as the C70 derivative without TR. We are currently engineering fullerenes without bulky side chains that are structurally the same as those previously described so that results obtained on inhibitory capabilities can be extrapolated to organelle targeting more specifically.

In conclusion, we have identified the ER as a primary organelle for 70-carbon based fullerene derivatives localization in human MC as opposed to previous publications which show 60-carbon based fullerenes localize to the mitochondria. This localization may help explain how the fullerenes exhibit their inhibitory activity through blunting of calcium and ROS spikes leading to subsequent reduction in histamine deganulation and cytokine production. Fullerenes are potent antioxidants and are being investigated as therapies for a wide range of diseases (24–26). This may have clinical implications for developing future fullerene-based compounds, our efforts are focused on developing these lead candidates into novel ways to treat those diseases associated with MC activation including asthma, arthritis, and anaphylaxis.

[Turnbuckle]

In conclusion, we have identified the ER as a primary organelle for 70-carbon based fullerene derivatives localization in human MC as opposed to previous publications which show 60-carbon based fullerenes localize to the mitochondria.

http://www.ncbi.nlm....pubmed/20138243

Based on my own experience taking a mix of C60 and C70, I'd say that what is true for C70 can't be automatically generalized to C60, and the findings of this paper may explain the difference.

Edited by Turnbuckle, 25 December 2012 - 02:48 PM.

[Turnbuckle]

As for the possibility that C60 could be stimulating the differentiation of stem cells, this is a good reason to use C60 infrequently, as adult stem cells could become depleted and not be there when you actually need them.

Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

http://www.scienceda...20531112620.htm

[Marty D]

In the same article, http://www.scienceda...20531112620.htm, in paragraph seven, they go on to say, "That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells' other major activity, Dr. Zhang said. He stressed that the inhibition doesn't cause them to create new stem cells but does preserve their potential to do so." Either I'm confused or Dr. Zhang is missing something (and I'm probably confused).

[Marty D]

stemcells.nih.gov has this information on page 4 of their Basics sheet:
http://stemcells.nih...ics/basics4.asp
"the origin of adult stem cells in some mature tissues is still under investigation."

From what I can gather, adult stem cells are considered limited, unless the cells are cancerous. So the article from Science Daily is referring to the generation of in vitro cultures or embryonic cells or something along those lines.

If the theory stating naturally occurring adult stem cells are limited is correct, and if C60oo is affecting the cell differentiation, it would indeed be good advice to use C60oo infrequently. And how limited is limited? Apparently enough to get one through to their mid 90's or so?

I still find the idea in the article confusing though since he is working toward limiting stem cells from becoming cancerous, apparently in adult stem cells, but at the same time refers to self renewal and the creation of new stem cells.

[Turnbuckle]

From what I can gather, adult stem cells are considered limited, unless the cells are cancerous. So the article from Science Daily is referring to the generation of in vitro cultures or embryonic cells or something along those lines.

When stem cells divide, they can form two new stem cells, a stem cell and a differentiated cell, or two differentiated cells. Obviously, if they did only the first they would get out of control, and if they did only the last, they'd become extinct. So there has to be some balance between self-renewal and differentiation.

Self-renewal is the process by which stem cells divide to make more stem cells, perpetuating the stem cell pool throughout life. Self-renewal is division with maintenance of the undifferentiated state. This requires cell cycle control and often maintenance of multipotency or pluripotency, depending on the stem cell. Self-renewal programs involve networks that balance proto-oncogenes (promoting self-renewal), gate-keeping tumor suppressors (limiting self-renewal), and care-taking tumor suppressors (maintaining genomic integrity). These cell-intrinsic mechanisms are regulated by cell-extrinsic signals from the niche, the microenvironment that maintains stem cells and regulates their function in tissues. In response to changing tissue demands, stem cells undergo changes in cell cycle status and developmental potential over time, requiring different self-renewal programs at different stages of life. Reduced stem cell function and tissue regenerative capacity during aging are caused by changes in self-renewal programs that augment tumor suppression. Cancer arises from mutations that inappropriately activate self-renewal programs.

http://www.annualrev...o.042308.113248

There is a relatively new idea that stem cell differentiation is driven by the mitochondria, and thus C60 may be indirectly acting by upregulating the metabolism of that organelle--

Stem cells are characterized by their multi-lineage differentiation potential (pluripotency) and their ability for self-renewal, which permits them to proliferate while avoiding lineage commitment and senescence. Recent studies demonstrate that undifferentiated, pluripotent stem cells display lower levels of mitochondrial mass and oxidative phosphorylation, and instead preferentially use non-oxidative glycolysis as a major source of energy. Hypoxia is a potent suppressor of mitochondrial oxidation and appears to promote "stemness" in adult and embryonic stem cells. This has lead to an emerging paradigm, that mitochondrial oxidative metabolism is not just an indicator of the undifferentiated state of stem cells, but may also regulate the pluripotency and self-renewal of stem cells. The identification of specific mitochondrial pathways that regulate stem cell fate may therefore enable metabolic programming and reprogramming of stem cells.

http://www.ncbi.nlm....pubmed/20809088

So you might expect C60 to use up stem cells by promoting differentiation, but would have no reason to expect it to create new stem cells.

Edited by Turnbuckle, 26 December 2012 - 02:20 PM.

[Marty D]

Thank you Turnbuckle. Somewhat clearer now. <g>

So how do you suppose your concept would play with Baati et all's mice? The much shorter lifespan probably has a strong role in stem cell biology?

[Turnbuckle]

Thank you Turnbuckle. Somewhat clearer now. <g>

So how do you suppose your concept would play with Baati et all's mice? The much shorter lifespan probably has a strong role in stem cell biology?

I think there are three modes of action--first as an antioxidant, second to rejuvenate mitochondria, and third by promoting the differentiation of stem cells (possibly by the second mode of action). The first mode of action was apparent in the Baati trial with CCl4. The study didn't test for oxygen utilization, but many here have noticed this and some have noticed effects that are suggestive of stem cell activation. So stem cells likely had some contribution to the longevity of the Baati rats.

Edited by Turnbuckle, 26 December 2012 - 05:05 PM.

[Marty D]

Well, that third leg does make dosing a difficult balancing act. The rats didn't have to worry so much but it seems like it might be possible to even shorten a human lifespan with overdosed regimen. Or make things worse toward the end. Maybe the C60 studies currently under way will consider taking some measurements. Or the next round of experiments if they need a before and after. Would be good information.

Hmm, cell differentiation kind of seems like the first prospect with real negative connotations for C60oo.

[Kevnzworld]

As for the possibility that C60 could be stimulating the differentiation of stem cells, this is a good reason to use C60 infrequently, as adult stem cells could become depleted and not be there when you actually need them.

Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

http://www.scienceda...20531112620.htm

Given your thoughts on stem cell differentiation and depletion, how have you altered your C60 dosing? I am currently dosing a small amount, now .8 mg daily every other week. I am thinking that even this might be too frequent.

[Turnbuckle]

As for the possibility that C60 could be stimulating the differentiation of stem cells, this is a good reason to use C60 infrequently, as adult stem cells could become depleted and not be there when you actually need them.

Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

http://www.scienceda...20531112620.htm

Given your thoughts on stem cell differentiation and depletion, how have you altered your C60 dosing? I am currently dosing a small amount, now .8 mg daily every other week. I am thinking that even this might be too frequent.

I keep my current dosing regime on my profile page -- 1.3 mg (15 micrograms/kg) once a week. My wife and I are presently doing the same dose. This may be too frequent as you say, but I'm continuing it to see if supplements to promote stem cell proliferation (3 or 4 times a week) will prove synergistic.

[Turnbuckle]

Well, that third leg does make dosing a difficult balancing act. The rats didn't have to worry so much but it seems like it might be possible to even shorten a human lifespan with overdosed regimen. Or make things worse toward the end. Maybe the C60 studies currently under way will consider taking some measurements. Or the next round of experiments if they need a before and after. Would be good information.

Hmm, cell differentiation kind of seems like the first prospect with real negative connotations for C60oo.

Yes, I agree. If there is stem cell depletion, that would be bad. Especially if you are younger and are sold on taking it every day as a magical antioxidant.

[niner]

There is a relatively new idea that stem cell differentiation is driven by the mitochondria, and thus C60 may be indirectly acting by upregulating the metabolism of that organelle--

Stem cells are characterized by their multi-lineage differentiation potential (pluripotency) and their ability for self-renewal, which permits them to proliferate while avoiding lineage commitment and senescence. Recent studies demonstrate that undifferentiated, pluripotent stem cells display lower levels of mitochondrial mass and oxidative phosphorylation, and instead preferentially use non-oxidative glycolysis as a major source of energy. Hypoxia is a potent suppressor of mitochondrial oxidation and appears to promote "stemness" in adult and embryonic stem cells. This has lead to an emerging paradigm, that mitochondrial oxidative metabolism is not just an indicator of the undifferentiated state of stem cells, but may also regulate the pluripotency and self-renewal of stem cells. The identification of specific mitochondrial pathways that regulate stem cell fate may therefore enable metabolic programming and reprogramming of stem cells.

So you might expect C60 to use up stem cells by promoting differentiation, but would have no reason to expect it to create new stem cells.

I don't know. In the quoted passage, they say that mitochondria may also regulate the self-renewal of stem cells. Maintaining the appropriate balance between replication and differentiation is under the control of multiple pathways, one of which is the mitochondria and associated metabotype. We have multiple observations that could be explained by stem cell differentiation, and a switch to OXPHOS is part of that. I don't know if we're seeing the rescue of failed or "stuck" differentiations, or if we're seeing an encouragement of differentiation that wouldn't otherwise have happened. If the latter, I don't think we have any way of knowing, at this point, whether it's too much differentiation or not, or if C60 might even be resulting in more replication, either directly or as a consequence of increased differentiation. I'd sure like to find some stem cell guys and get them to run a few experiments.

What we do know, at this point, is that Baati's rats lived a lot longer, and they got large intermittent doses. At the moment, I'm five weeks out from the midpoint of 17.5mg spread over a week. I'm running a mini-experiment, looking to see if there's any obvious decay in the various things that I've noticed after taking C60. Things still seem to be holding up, as far as I can tell given holiday drinking and eating, lack of working out and a mild cold. Some time soon, I'll be taking a bolus of 10-15mg and waiting another 4-8 weeks.

[mikey]

FYI: I take 7 mg every day and have since August. I just saw a health care practitioner that I haven't seen since before I started C60oo.
The first thing out of his mouth was you look younger. I said, "What looks younger?" He said, "You have less wrinkles. You look maybe 2 or 3 years younger." Another friend who I hadn't seen since before I started C60 said basically the same thing.

So, I'm putting in a note about continuous dosing producing an anti-aging skin result, at the very least.

[Nootropic Cat]

Well, that third leg does make dosing a difficult balancing act. The rats didn't have to worry so much but it seems like it might be possible to even shorten a human lifespan with overdosed regimen. Or make things worse toward the end. Maybe the C60 studies currently under way will consider taking some measurements. Or the next round of experiments if they need a before and after. Would be good information.

Hmm, cell differentiation kind of seems like the first prospect with real negative connotations for C60oo.

Yes, I agree. If there is stem cell depletion, that would be bad. Especially if you are younger and are sold on taking it every day as a magical antioxidant.

Hmm, these recent posts have me wondering whether I'm taking too much. I've been dosing 11.25mg, once every two weeks. Any thoughts on this? I'm 31 fwiw.

[Turnbuckle]

"...You look maybe 2 or 3 years younger." Another friend who I hadn't seen since before I started C60 said basically the same thing.

So, I'm putting in a note about continuous dosing producing an anti-aging skin result, at the very least.

I get 2-3 from different mirrors in the house. 10-20 should be your goal.

[Turnbuckle]

Well, that third leg does make dosing a difficult balancing act. The rats didn't have to worry so much but it seems like it might be possible to even shorten a human lifespan with overdosed regimen. Or make things worse toward the end. Maybe the C60 studies currently under way will consider taking some measurements. Or the next round of experiments if they need a before and after. Would be good information.

Hmm, cell differentiation kind of seems like the first prospect with real negative connotations for C60oo.

Yes, I agree. If there is stem cell depletion, that would be bad. Especially if you are younger and are sold on taking it every day as a magical antioxidant.

Hmm, these recent posts have me wondering whether I'm taking too much. I've been dosing 11.25mg, once every two weeks. Any thoughts on this? I'm 31 fwiw.

Do you have specific health problems? If not, you have plenty of time to let other people experiment with this.

[niner]

Hmm, these recent posts have me wondering whether I'm taking too much. I've been dosing 11.25mg, once every two weeks. Any thoughts on this? I'm 31 fwiw.

That's not a crazy amount, and I like the idea of intermittent dosing. You could dial the dose back, or you could stop altogether. I don't have the luxury of waiting ten or fifteen years for this to all shake out, and I have the background to make an informed decision about it (not that I'm guaranteed a good outcome). I'm also getting immediate benefits that at your age you probably wouldn't notice. If you were to wait five years, you'd still be young enough to get most of the benefits, assuming they exist, and our knowledge base should be a lot better at that point. I'm not particularly worried about stem cell depletion. That's a hypothetical concern, but I think the odds of it are low. If Baati's rat's suffered from stem cell depletion, it didn't seem to hurt them. Rats aren't people, although they are a lot closer to people than flies or worms.

[Nootropic Cat]

Thanks guys. No specific health problems, but I do feel the tiniest bit of urgency given that I'm getting to the point where aging is likely to 'kick in', and I'm worried that the smoking and heavy drinking that plagued most of my adult life may have fast-tracked things somewhat. I dunno, it's tough to evaluate the risks and rewards; I feel like I've picked up a bunch of extra tickets for the cancer raffle and would love to do something that might get rid of them.

[daouda]

I also take C60, 1.6 mg daily, biweekly.

What do you mean by that? 1.6mg once every two weeks, or 1.6mg once a day for a week then one week off and repeat?

Edited by daouda, 27 December 2012 - 04:32 PM.

[Kevnzworld]

I also take C60, 1.6 mg daily, biweekly.

What do you mean by that? 1.6mg once every two weeks, or 1.6mg once a day for a week then one week off and repeat?

The latter. I am considering dropping it to .8mg daily.. ( every other week ).