214 replies to this topic

[Gerald W. Gaston]

Dr. Stephen Spindler (University of California Riverside) presents preliminary information on compounds that mimic calorie restriction and result in increases in Lifespan in Mice. OAA (oxaloacetic acid, benaGene ^TM) was one of the leading compounds to increase lifespan. We shall continue to follow Dr. Spindler's work to see if his initial results continue. See his presentation on calorie restriction mimetics at the Manhattan Beach Project Longevity Conference in Miami in November 2009:



There are some other great videos you may want to watch as part of the conference also.

Good video. He mentions BenaGene early on but doesn't want to plug it again by company name at the end. :-) He states no one knows how it works but I see you have attempted to explain it to some degree here.

His warning about 'combinations' that starts @~6min in is just more confirmation of the complexity of using multiple drugs and supplements.

[tunt01]

His warning about 'combinations' that starts @~6min in is just more confirmation of the complexity of using multiple drugs and supplements.

yea, i thought this explanation was thoughtful. another knock against the ray kurzweil's of the world.

also kind of interesting that they are seeing positive results from SAMe.

thx for posting the link, alan.

Edited by prophets, 31 December 2009 - 06:47 PM.

[niner]

Also seeing a positive result for both a statin () and some blood pressure drug, and not seeing positive results for TA65. Interesting.

[AgeVivo]

Dr. Stephen Spindler (University of California Riverside) presents preliminary information on compounds that mimic calorie restriction and result in increases in Lifespan in Mice. OAA (oxaloacetic acid, benaGene ^TM) was one of the leading compounds to increase lifespan. We shall continue to follow Dr. Spindler's work to see if his initial results continue. See his presentation on calorie restriction mimetics at the Manhattan Beach Project Longevity Conference in Miami in November 2009:



There are some other great videos you may want to watch as part of the conference also.

Great video indeed. No result is statistically significant...yet...
Here is the list of compounds under test, by Stephen Spindler and by the IPT, on pre-aged-mouse lifespan:
http://www.imminst.o...o...st&p=371453

Edited by AgeVivo, 01 January 2010 - 12:05 AM.

[maxwatt]

This paper explains much of what is going on with the malate/oxaloate proton shuttle and NAD; it also suggests that aspartic acid may also be as beneficial, though there seem to be no life-span tests for aspartic acid.

Genes Dev. 2008 Apr 1;22(7):931-44.
The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast.
Easlon E, Tsang F, Skinner C, Wang C, Lin SJ.

Section of Microbiology, College of Biological Sciences, University of California at Davis, Davis, California 95616, USA.
Recent studies suggest that increased mitochondrial metabolism and the concomitant decrease in NADH levels mediate calorie restriction (CR)-induced life span extension. The mitochondrial inner membrane is impermeable to NAD (nicotinamide adenine dinucleotide, oxidized form) and NADH, and it is unclear how CR relays increased mitochondrial metabolism to multiple cellular pathways that reside in spatially distinct compartments. Here we show that the mitochondrial components of the malate-aspartate NADH shuttle (Mdh1 [malate dehydrogenase] and Aat1 [aspartate amino transferase]) and the glycerol-3-phosphate shuttle (Gut2, glycerol-3-phosphate dehydrogenase) are novel longevity factors in the CR pathway in yeast. Overexpressing Mdh1, Aat1, and Gut2 extend life span and do not synergize with CR. Mdh1 and Aat1 overexpressions require both respiration and the Sir2 family to extend life span. The mdh1Deltaaat1Delta double mutation blocks CR-mediated life span extension and also prevents the characteristic decrease in the NADH levels in the cytosolic/nuclear pool, suggesting that the malate-aspartate shuttle plays a major role in the activation of the downstream targets of CR such as Sir2. Overexpression of the NADH shuttles may also extend life span by increasing the metabolic fitness of the cells. Together, these data suggest that CR may extend life span and ameliorate age-associated metabolic diseases by activating components of the NADH shuttles.

PMID: 18381895

Edited by maxwatt, 03 January 2010 - 04:09 PM.

[medievil]

Can anyone tell me which supplements they started to see results with? English isnt my main language and i dont understand some things this guy is saying.

Thx!

[Hedrock]

Thermically stabilized oxaloacetate?

Haha, that's funny. They are selling water and CO2?

[Gerald W. Gaston]

Looks like AOR's Ortho Glucose II no longer has benaGene in it:

Now on AOR's website:

Vanadyl Sulfate 100 mg
Pine Bark Extract (95% Proanthocyanidins) 125 mg
Chromium (trivalent Cr picolinate) 600 mcg
Cinnamon Extract 66 mg
Gymnemma Sylvestre Extract 300 mg
Bitter Melon Extract (Momordica Charantia) 255 mg
Corosolic acid 500 mcg
R(+)-Lipoic Acid 300 mg

Previous (still listed as such on CureSelf's product page):
BMOV (bis[maltolato]oxovanadium IV) 30mg
Chromium (trivalent Cr picolinate) 600mcg
Cinnamon Extract 66mg
Gymnemma Sylvestre Extract 300mg
Bitter Melon Extract (Momordica Charantia) 255mg
DNJ (1-deoxynojirimycin [from mulberry extract]) 18mg
benaGeneTM (3-carboxy-3-oxopropanoic acid) 100mg
Pine Bark Extract (95% Proanthocyanidins) 125mg

[tunt01]

what do we know about Corosolic Acid (replacement for benagene)?

Edited by prophets, 06 January 2010 - 06:54 PM.

[Gerald W. Gaston]

what do we know about Corosolic Acid (replacement for benagene)?

I don't believe any of the ingredients are a direct replacement for benaGene. From what I read, admittedly most of it some time ago, there is little human research (a few small studies that showed a statistical significance at 90 min after consumption) on the use of Corosolic Acid... which is commonly extracted from lagerstroemia speciosa (crape myrtle/banaba). NOW GlucoFit has ~ 240mcg of it.

http://www.drugs.com...solic-acid.html

[tintinet]

Still in Mito Charger:


"The ingredient BenaGene ® contains a key intermediate in the Kreb's Cycle. Studies demonstrate that benaGene mimics a caloric restriction diet, which has been shown to increase the expression of beneficial genes associated with increased life span, health span, weight management and blood glucose reduction.

180 Vegi-Caps 383 mg
100% Vegetarian
SUPPLEMENT FACTS
Serving Size: 6 Capsules

R(+)-Lipoic Acid 150 mg
Co-Enzyme Q10 100 mg
Rhodiola Rosea (min 3% rosavins, 1% salidroside) 150 mg
Benfotiamine 150 mg
Oxaloacetic acid (Benagene ®)100 mg
D-Uridine 50 mg
Gymnostemma Pentaphyllum Extract 100 mg
Acetyl-L-Carnitine 1500 mg

Suggested use: Take 6 capsules daily with food, or as directed by a qualified health care practitioner. "

[Gerald W. Gaston]

Still in Mito Charger:


"The ingredient BenaGene ® contains a key intermediate in the Kreb's Cycle. Studies demonstrate that benaGene mimics a caloric restriction diet, which has been shown to increase the expression of beneficial genes associated with increased life span, health span, weight management and blood glucose reduction.

Yes I confirmed that it is still listed as such on the write-up at RI the same day I checked on the Glucose II product. But as with last time I could only find this info on RI website and not AOR's website. Did you look at the one at RI or did you find it directly from AOR? Because as with CureSelf there is always the possibility that they are selling out the old inventory or just haven't update the product page.

[kitinje]

Dr. Stephen Spindler (University of California Riverside) presents preliminary information on compounds that mimic calorie restriction and result in increases in Lifespan in Mice. OAA (oxaloacetic acid, benaGene ^TM) was one of the leading compounds to increase lifespan. We shall continue to follow Dr. Spindler's work to see if his initial results continue. See his presentation on calorie restriction mimetics at the Manhattan Beach Project Longevity Conference in Miami in November 2009:



There are some other great videos you may want to watch as part of the conference also.

Does anyone know when are Spindler's final results to be expected?

[pycnogenol]

Gymnostemma Pentaphyllum Extract 100 mg

This ingredient also goes by the name Jiaogulan.

[curious_sle]

Please pardon my ignorance but has anyone an idea if taking methylene blue together with benagene does interact potentiate or cancel each others efects out? I already tak Benagene now that it i quite affordable and would like to add methylene blue (though not into mixing it down myself but yeah. maybe someone enterprising will provide a usefull supplement sometime soon?).

Thank you for enlightening remarcs.

[stephen_b]

Did anyone see that Benagene is also an ingredient in AOR's Mito-Charger (link to RI; I wonder why that product isn't on AOR's website aor.ca).

edit: whoops, didn't see tintinet's post

Edited by stephen_b, 18 March 2010 - 04:34 PM.

[stephen_b]

I received an response from AOR about why mito-charger is not on their site aor.ca. It contains carnitine, which they are not allowed to put in their product in Canada. Mito-charger is on their US site (aorhealth.com), which I didn't know existed.

[peteo]

So any one think this stuff is worth taking?

[stephen_b]

It seems to compete primarily with LEF's Mitochondrial Energy Optimizer. As I see them, the pluses are: if you want to take benagene (oxaloacetic acid) anyway, it has a lot of things that you might be taking separately. It contains uridine and the herb Gynostemma pentaphyllum (I don't know much about these two). Negatives: no carnosine, perhaps more benfotiamine than some would like (though the same as LEF's), and the suggested dose is 6 capsules. AOR is cheaper per serving by quite a bit though for purchases of one bottle: LEF $2.15 per serving vs AOR $1.23 per serving. But if you figure in the cost of carnosine that you'd have to buy separately, AOR's cost goes up to $1.90 (using Jarrow carnosine for comparison).

[Sillewater]

Exp Gerontol. 2010 Jun;45(6):395-9. Epub 2010 Mar 10.
NAD(+) and metabolic regulation of age-related proteoxicity: A possible role for methylglyoxal?
Hipkiss AR.

The University of Birmingham, Edgbaston, UK. alanandjill@lineone.net
Abstract
A common biochemical characteristic of aging is proteotoxicity i.e. the accumulation of altered proteins. While many studies have shown that NAD(+) is important when lifespan is modulated by dietary means, it is uncertain whether or how NAD(+) affects either formation or elimination of altered proteins. It is suggested here that changes in NAD(+) availability can affect generation of methylglyoxal (MG) from glycolytic intermediates, which in turn can damage proteins, promote generation of reactive oxygen species and induce mitochondrial dysfunction. The proposal can also help to explain how, by altering NAD(+) regeneration from NADH, dietary supplementation with glycerol or glucose, which decreases lifespan in the nematode Caenorhabditis elegans, could cause MG generation to increase, whereas oxaloacetate supplementation, which increases lifespan, could lower the potential for MG formation. The proposal also suggests how upregulation of mitogenesis and mitochondrial activity, and increased aerobic activity, help to decrease the potential for MG formation and resultant proteotoxicity, with consequential beneficial effects with respect to aging. 2010 Elsevier Inc. All rights reserved.

PMID: 20226237 [PubMed - in process]

[neuropill]

Curious on any update on this novel antiaging compound. All I can find is AOR's articles here http://www.aor.ca/ht....php?id=31#ani2 which suggests some human studies were done showing positive benefits.

Ahh some study data is published here.

http://www.benagene....cose_management

Edited by neuropill, 09 August 2012 - 11:12 AM.

[smithx]

A study came out this year that's of interest:

J Gerontol A Biol Sci Med Sci. 2012 Mar 26. [Epub ahead of print]
Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice.
Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE.
Source

Department of Pharmacology and Barshop Institute for Longevity and Aging Studies, 15355 Lambda Drive, University of Texas Health Science Center at San Antonio, TX 78245. strong@uthscsa.edu.
Abstract

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

PMID:
22451473
[PubMed - as supplied by publisher]

[neuropill]

A study came out this year that's of interest:

J Gerontol A Biol Sci Med Sci. 2012 Mar 26. [Epub ahead of print]
Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice.
Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE.
Source

Department of Pharmacology and Barshop Institute for Longevity and Aging Studies, 15355 Lambda Drive, University of Texas Health Science Center at San Antonio, TX 78245. strong@uthscsa.edu.
Abstract

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

PMID:
22451473
[PubMed - as supplied by publisher]

I wonder if they use a high enough dose as it clearly showed antiaging effects in this mice study and they started at 9 months.


"
In a pilot test, C57BL/6 male mice were started on a benaGene supplemented diet starting at age 9 months (approximately 1/3 through their lifespan). Male mice were used as they typically have a shorter lifespan than females. At the 50% mortality mark, benaGene supplementation increased lifespan by 23% as compared to the control group. The increase in "residual lifespan" (from the date benaGene was added to the diet) was 39%. The increase in maximal lifespan over the oldest living member of the control group was 14%.
In addition to an increase in Lifespan, the benaGene supplemented mice also showed an increase in health span with decreased inflammation, reduced curvature of the spine, and less graying of the fur.
Larger scale tests are in progress with the US National Institute of Aging (NIA) through the "Interventions in Aging" program."

Edited by neuropill, 14 August 2012 - 06:28 AM.

[hamishm00]

I took Benegene 300mg a day for a year. I noticed no increases in energy or decreases in weight, or any other benefit or effect.

I really like the theory/science behind the product, but hate the retail price which is very high.

The benefit vs the cost just doesn't seem to add up.

I've dropped it from the regimen. Would pick it back up if it went closer to 15-20 dollars a bottle.

[neuropill]

I took Benegene 300mg a day for a year. I noticed no increases in energy or decreases in weight, or any other benefit or effect.

I really like the theory/science behind the product, but hate the retail price which is very high.

The benefit vs the cost just doesn't seem to add up.

I've dropped it from the regimen. Would pick it back up if it went closer to 15-20 dollars a bottle.

Did you take any blood tests to measure it's effects on your average fasting glucose during your year of use? From the human research that's available that seems like the easiest way to measure some of it's effectiveness. I'm curious what you expected to feel or what you were taking it for?

To me i don't really expect to and have not felt a major change from certain antiaging supplements. Carnosine, R-Lipoic, etc I take it for the science and do various blood testing to scientifically measure any effects.

Overall this compound looks overlooked and covers an novel pathway so it appeals to me. AOR's bottle is $35 for a month supply which isn't that bad but it suggests 100mg daily so I'm curious what made you take 300 mg? I could see it being abit much if you're taking 3 times the recommended dose.

Thanks for your opinion.

Edited by neuropill, 15 August 2012 - 12:16 AM.

[hamishm00]

I check my glucose relatively regularly - Oxaloacetic acid at 300mg had no impact on fasting glucose.

I disagree with regards to noticing effects of supplements beyond blood testing. Carnosine and beta-alanine made a significant impact on gym performance and sense of smell. Carnosine is likely to have other benefits which would be noticeable over the long term, especially in relation to glycation and age related muscle sarcopenia.

My biggest beef with Benegene is pricing - 35 dollars for 3 grams of oxaloacetic acid? really? With the greatest of respect to Mr A. Cash and AOR, that's way too expensive.

I don't think that 100mg is a dose that will have much impact on anything (including Nad+/Nadh ratio, krebs cycle, glucose etc). it could be an important long term anti-aging strategy at the right dose, which is not likely to be 100mg (Aubrey de Grey made a comment along these lines on his forum) and at the right price.

[neuropill]

I check my glucose relatively regularly - Oxaloacetic acid at 300mg had no impact on fasting glucose.

I disagree with regards to noticing effects of supplements beyond blood testing. Carnosine and beta-alanine made a significant impact on gym performance and sense of smell. Carnosine is likely to have other benefits which would be noticeable over the long term, especially in relation to glycation and age related muscle sarcopenia.

My biggest beef with Benegene is pricing - 35 dollars for 3 grams of oxaloacetic acid? really? With the greatest of respect to Mr A. Cash and AOR, that's way too expensive.

I don't think that 100mg is a dose that will have much impact on anything (including Nad+/Nadh ratio, krebs cycle, glucose etc). it could be an important long term anti-aging strategy at the right dose, which is not likely to be 100mg (Aubrey de Grey made a comment along these lines on his forum) and at the right price.

I wonder why it didn't work for you but did for those in the study. Perhaps there was a difference in dosage or other supplements you were taking effected it.

I've noticed nothing with L-Carnosine that I can measure without blood tests and I'm not sure how anyone can really know especially if they are taking several supplements what is causing an effect or placebo. It seems too subjective and not well controlled. I have never heard anyone notice the effects of inhibiting glycation.

I don't think it's any more expensive than carnosine or TA-65. I'm happy they are providing these compounds to us and doing research as well. To each his own with what they can afford or what they believe is worthwide.

I'm confused about your dosage what exactly is it based on if not the human studies? I was going to start with 100 mg and measure my glucose and go from there.

[tintinet]

Has anyone here, outside of the beneGENE reported study, reported any measurable effects on blood glucose?

[AgeVivo]

http://www.youtube.com/watch?v=aIlA-QB8m0A
Does anyone know when are Spindler's final results to be expected?

Dear All,

Prof Spindler will come and present at the conference we are organising in December in Brussels: http://www.eha2012.org/

Best,
AgeVivo

[AgeVivo]

http://www.youtube.com/watch?v=aIlA-QB8m0A
Does anyone know when are Spindler's final results to be expected?

Dear All,

Prof Spindler will come and present at the conference we are organising in December in Brussels: http://www.eha2012.org/
I truly believe that this type of work will make us live longer and healthier. We need more of such great work!!!

Best,
AgeVivo

PS: list of compounds he had presented during the October 2010 conference: http://www.longecity...453#entry371453
PS: list of compounds under testing at the ITP: http://www.nia.nih.g...mpounds-testing