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New research on metformin


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#1 kismet

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Posted 25 August 2008 - 12:59 AM


When doing some research I stumbled over this goodie, it seems pretty recent:
Blagosklonny MV, Campisi J.
Cancer and aging: More puzzles, more promises?
Cell Cycle. 2008 Sep 16;7(17). [Epub ahead of print]
PMID: 18719390 [PubMed - as supplied by publisher]
FULL: http://www.landesbio...cc/article/6626

We do have a thread on metformin and its effect on longevity. Lucid summed up the influence of metformin on short lived HER-2/neu mice as shown by Anisimov et al, it seems like this paper summarizes another study by them. Is this another proof of metformin being a true life extension drug?  (To me it all seems kinda fishy...)

“Unexpectedly, metformin did not decrease the incidence of cancer in this mice strain.. [it] increased mean life span by >37% and increased maximum life span by >10 months. Further, metformin extended the mean life span of the longest-living animals in the study population (the last 10% of survivors) by >20%.”
The study was performed in female SHR mice, Anisimov et al. reported in another paper (study on Epitalon) a mean life span of 450 and maximum life span of around 700d for untreated SHR mice, so that's a pretty long-lived strain, though they develop hypertension. However, in this paper the mean life span is described as being 290d in the control group, bad husbandry maybe?
And I can only guess why they only use female mice..

The author's take: “…it is possible that metformin did not affect a fundamental aging process per se, but rather one or more phenotype closely associated with aging…metformin did not decrease insulin levels, which rose 10-fold with age in both control and metformin-treated mice…failed to alter…blood glucose and cholesterol levels and body temperature. Thus, metformin might have only partial anti-aging effects.”
Proposed mechanism of action:
"Metformin is known to activate AMPK, which in turn inhibits TOR (target of rapamycin), thus restoring insulin sensitivity. "
It seems the NIH is performing a study on rapamycin so all in all it sounds quite promising. 

#2 mikeinnaples

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Posted 25 August 2008 - 12:33 PM

I have been looking at metformin as an addition to my routine, I am just not sure of the benefits to someone completely health. I have read some of the literature, but I honestly couldn't tell you if the cost+risk : benefit ratio is worth it.

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#3 kismet

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Posted 25 August 2008 - 01:43 PM

Does anyone know how trustworthy Vladimir N. Anisimov is? How come no one ever reproduces his experiments like the study on epitalon? They did publish in the journal biogerontology though, how good is their peer-review?

BTW the national institute on aging is testing resveratrol, green tea, curcumin, rapamycin and several other compounds I'm not familiar with for life extension. I think Michael has posted an interesting summary of one of the trials over at the M-forums. http://mfoundation.o...p=4170#post4170

Yes, I think Metformin is still a gamble. It's a drug with potentially serious side effects and there's not even high-quality research on rodents yet.

#4 Michael

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Posted 21 September 2008 - 10:11 PM

When doing some research I stumbled over this goodie, it seems pretty recent:
Blagosklonny MV, Campisi J.
Cancer and aging: More puzzles, more promises?
Cell Cycle. 2008 Sep 16;7(17). [Epub ahead of print]
PMID: 18719390 [PubMed - as supplied by publisher]
FULL: http://www.landesbio...cc/article/6626

We do have a thread on metformin and its effect on longevity. Lucid summed up the influence of metformin on short lived HER-2/neu mice as shown by Anisimov et al, it seems like this paper summarizes another study by them. Is this another proof of metformin being a true life extension drug? (To me it all seems kinda fishy...)

Well, it clearly can't be another such proof, since the first study (1,2) clearly was not: HER-2/neu mice are thus called for bearing extra transgenic HER2 (epidermal growth factor receptor 2), an oncogene that increases breast cancer aggressiveness; it's the scary one targeted by Herceptin (trastuzumab) (HERceptin -- get it?). Unsurprisingly, such mice die very early of mammary tumors. This purported "life extension" effect is again merely the partial normalization of a shortened lifespan: "Only one control mouse (3%) survived the age of 10 months whereas 9 mice (28%) survived this age in metformin-treated group (p<0.001)." (1). Again: the historical benchmark for lifespan in genetically normal, well-nourished, nonobese, well-cared-for laboratory mice is ~900 d mean and ~1200 d max (10th-decile survivorship). Bringing the life of such mice closer to normal is not something that should be taken as noteworthy from the perspective of humans without a family history of dying in their 50s of similar causes. I'm sure Herceptin would help these miserable critters too, but that's of little interest to the science of life extension.

As to the newer study in SHR mice (3):

“Unexpectedly, metformin did not decrease the incidence of cancer in this mice strain.. [it] increased mean life span by >37% and increased maximum life span by >10 months. Further, metformin extended the mean life span of the longest-living animals in the study population (the last 10% of survivors) by >20%.”
The study was performed in female SHR mice, Anisimov et al. reported in another paper (study on Epitalon) a mean life span of 450 and maximum life span of around 700d for untreated SHR mice, so that's a pretty long-lived strain, though they develop hypertension. However, in this paper the mean life span is described as being 290d in the control group, bad husbandry maybe?

Curious -- and I see another study with unexpectedly short-lived animals in a previous study from the same laboratory: (4) was in C3H/Sn mice (standard nomenclature would be C3H/HeSn), which suffers retinal damage and for which I could not find longevity data, but that based on its background "ought" to have a nomral LS; yet in (4), their mean and max LS (487 and 691 d, respectively) were no better than for SHR. I had the impression that Anisimov was a fine bench scientist, albeit a weak theoretician (since he keeps drawing conclusions about aging from the partial normalization of the abnormally-shortened lifespans of various mutant strains of mice), and is therefore doing a great job in the execution of the wrong experiments, and then drawing the wrong conclusions from the results -- but now I'm not sure.

I'm sure, IAC, that you can guess my response to this latest study (3). A mean and max LS of 450 and 700 d is definitely not "pretty long lived": if we take 450 and 700 d as normal for the strain, only live about half as long as they 'ought' to. I'd say we can safely ignore this report.

And I can only guess why they only use female mice..

Well, it's normal in LS studies to use only one gender, since in rodents as in humans females usually live longer than males; it's more common to pick males, because they are thought to be 'less complicated' because there's no estrus or menopause, but OTOH a result in the more longevous gender might reasonably be thought more informative about aging.

The author's take: “…it is possible that metformin did not affect a fundamental aging process per se, but rather one or more phenotype closely associated with aging…metformin did not decrease insulin levels, which rose 10-fold with age in both control and metformin-treated mice…failed to alter…blood glucose and cholesterol levels and body temperature. Thus, metformin might have only partial anti-aging effects.”

That's a pretty vacuous response: any number of things modify any number of parameters that change with aging; that doesn't make hypertension or diabetes drugs 'partial anti-aging agents'.

References
1. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG,
Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M,
Re F, Franceschi C.
Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.
Exp Gerontol. 2005 Aug-Sep;40(8-9):685-93.
PMID: 16125352

2. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, Re F, Franceschi C.
Abstract
Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.
Exp Gerontol. 2005 Aug-Sep;40(8-9):685-93.
PMID: 16125352 [PubMed - indexed for MEDLINE]

3. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, Semenchenko AV.
Metformin slows down aging and extends life span of female SHR mice.
Cell Cycle. 2008 Sep;7(17):2769-73. Epub 2008 Sep 11.
PMID: 18728386 [PubMed - in process]

4. Dilman VM, Anisimov VN.
Abstract
Effect of treatment with phenformin, diphenylhydantoin or L-dopa on life span and tumour incidence in C3H/Sn mice.
Gerontology. 1980;26(5):241-6.
PMID: 7390164 [PubMed - indexed for MEDLINE]

#5 kismet

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Posted 16 December 2008 - 12:23 AM

I understand your concerns. I'm baffled myself, why do they (Anisimov et al) always repeat the same experiments in the same or similar short lived strains instead of C57BL/6 mice for instance. Either they are really misinformed or they know something that we don't know - that the compound would fail in a rigorous, scientific life-span study maybe?
Looking back at my post it seems I've used the term "pretty long lived" too generously due to my optimism, my bad.

I just want to find out whether we should further waste our resources* on this substance e.g. try to replicate the data with our "Mprize@home" project or get some researchers to carry out some real aging-studies (maybe propose it for the NIA's Intervention Testing Program).
I hope you are not dismissing putative CR-mimetics, just because you are already on CR (is this even a conflict of interest per se?) I believe you don't, but I like to point out possible sources of bias regardless.

* I am not talking about diverting resources from basic research into aging and SENS, the most important piece of the puzzle. Just using available resources.

Assuming I read this (from sci.life-ex) correctly, as I skimmed some of the discussion, there was another supposed life-extension report by Roth et al from the “Symposium on Neurobiology and Neuroendocrinology of Aging”, both the symposium and your post on the topic date back to 2002. I'm wondering what happened? Do you still consider their work to be legitimate? Does it merit further investigation?

For the time being I will post "encouraging" results in diabetics, even if diabetes per se increases all cause mortality, it's nice to see that metformin decreases all-cause mortality as would be expected from a true life-extension drug. However, we need to find out if the benefits are coming merely from a reversed diabetes phenotype or real life-extending properties.

”Treatment of type 2 diabetes with regimens containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with regimens without metformin.” [1]
”Treatment with metformin hydrochloride was associated with a decreased risk of cardiovascular mortality (pooled OR, 0.74; 95% CI, 0.62-0.89) compared with any other oral diabetes agent or placebo; the results for cardiovascular morbidity and all-cause mortality were similar but not statistically significant… lack of power prohibited firmer conclusions” [2]

Any discussion on the issue is welcomed, I would particularly appreciate some input on diabetes. Does it result in increased all-cause mortality? How much? Are the decreased risks from metformin "impressive" or just "meh" under those circumstances?

[1] Am J Med Sci. 2008 Sep;336(3):241-7.
Effect of metformin-containing antidiabetic regimens on all-cause mortality in veterans with type 2 diabetes mellitus.
Gosmanova EO, Canada RB, Mangold TA, Rawls WN, Wall BM.
[2] Arch Intern Med. 2008 Oct 27;168(19):2070-80.
Cardiovascular outcomes in trials of oral diabetes medications: a systematic review.
Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS, Feldman L, Vassy J, Wilson R, Bass EB, Brancati FL.
Full: http://archinte.ama-...ull/168/19/2070

#6 Michael

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Posted 09 February 2009 - 07:35 PM

All:

Just seeing this now:

I just want to find out whether we should further waste our resources* on this substance e.g. try to replicate the data with our "Mprize@home" project or get some researchers to carry out some real aging-studies (maybe propose it for the NIA's Intervention Testing Program).

I think that the preliminary data on metformin makes it worthwhile to have it properly tested (see below), but I can't imagine that anyone's going to do so "@home": according to this source, which is however for breeding females (which are doubtless somewhat more expensive than non-bred females, or males), teh cost to maintain a lab mouse is "$530/year (includes cost of technician, cage washing, bedding, feed, other supplies, but not the cost of genotyping", and to get statistically significant LS results requires more than 30 animals (more than 40 would be better, and more is better still) in both the control and the experimental goups to get a statistically significant results, so you're looking at something like US$37100 per annum, which you'd have to have dedicated for 4 y (or more, if the intervention is wildly successful) -- so, more than US$150 k. And as the number of lousy LS results that we've seen even in academic labs (where the "extension" is relative to a colony of otherwise long-lived mice that for reasons that are often unclear (tho' overfeeding is a common one) live shorter than they should) has shown us, even "real scientists" don't always do a credible job of animal husbandry, let alone we amateurs. And then, even if it really, unambiguously did work, the absence of formal institutional oversight (scientific and ethical) might lead to skepticism and/or hostility about the research and its results, delaying peer-reviewed publication, replication, and ultimate human translation for a difficult-to-anticipate period of time.

I hope you are not dismissing putative CR-mimetics, just because you are already on CR (is this even a conflict of interest per se?) I believe you don't, but I like to point out possible sources of bias regardless.

I don't see why you'd think of my CR practice would bias me against a mimetic: if anything, being sufficiently convinced that rodent CR data will translate into human results ought to make me about as bullish as anyone can be of the benefits of such an agent, and having a pill would really save me a lot of time and hassle. Indeed, if I was against doing it in a pill, I'd probably have a problem with SENS, too. No, I spelled out my reasons for thinking the mimetic approach is going nowhere in (3) and (4), to some extent in Ending Aging, and in more detail in an unpublished MS from which an extract was posted privately here (I believe that this is closed to all but Imminst Directors & Advisors, and ask people not to cross-post it to any public forum or otherwise circulate it in order to avoid impeding ultimate publication). To quote from (3):

Such agents are, first, likely to have unacceptable side-effects, as they will of necessity induce the dramatic metabolic shift which underlies both the desired and the undesired effects of CR. This is as we would expect from evolutionary theory (Kirkwood and Austad [ref]) . The signaling pathways in which such agents would intervene are normally set to maximize reproductive fitness, even at the expense of long-term somatic health, and thus exert pleiotropic effects on the health of the organism. If these pathways could be manipulated to retard our rate of aging at no cost to the “normal,” apparently “healthy” functioning of the organism within the parameters of our existing genetic toolkit, such adjustments would already have been made, as they would increase reproductive fitness. ...

Secondly, CR mimetics will be extraordinarily difficult to license for clinical use in humans, not only because of the regulatory hurdles facing a pharmaceutical designed to treat “aging,” but because they will (like CR itself) only retard the further accumulation of aging damage rather than reversing it. Prevention, rather than treatment, of age-related disease is by its nature a longer-term clinical endpoint. Thus, even extrapolating from the surprisingly positive results of Spindler’s group’s latest work in older animals (Dhahbi et al [ref]), any such drug will take many times the length of time usually required of existing pharmaceuticals to reveal clinically-significant benefits on “licensable” indications in its users.

Indeed, there is a definite irony to the fact that, as essentially preventive agents, CR mimetic drugs would at once be most likely to benefit patients if administered while they are still young and healthy, and yet be all the more difficult prove effective for any clinical outcome in such patients. And while the multi-decade efficacy trials proceed, such subjects will yet be forced to endure the great majority of the drug’s side-effects. Ethical review panels will be especially wary of approving clinical trials using agents whose safety and efficacy will not be clear for decades in young, healthy subjects. Thus, the time lag will be even greater before the full benefits of a true CR mimetic, as envisioned eg. by Richard Miller [ref], would be manifested in the clinic, in patient lives, and in reduced burden on public and private medical systems.(3)

The first point above is mathematically modeled in (5), with contradistinction to a damage-removal, "engineering"/SENS approach:
Posted Image

Figure 1. Blue line: therapy that reduces the rate of damage accumulation by 50% without removing pre-existing damage. Green line: effect of progressively doubling the efficacy of such an intervention every 7 years. Pink line: "engineering"/SENS therapy that removes half the damage. Orange line: progressive refinement of such a therapy to remove half the damage that it previously could not remove every 20 y. From (5).

* I am not talking about diverting resources from basic research into aging and SENS, the most important piece of the puzzle. Just using available resources.

I think you mean vice-versa, right? Either way: dude, it's all one bathtub ...

Assuming I read this (from sci.life-ex) correctly, as I skimmed some of the discussion, there was another supposed life-extension report by Roth et al from the “Symposium on Neurobiology and Neuroendocrinology of Aging”, both the symposium and your post on the topic date back to 2002. I'm wondering what happened? Do you still consider their work to be legitimate? Does it merit further investigation?

I'm sorry that you only saw that post ... The study turned out to be a disappointment. Ingram et al never published the results, and the problem on that fuzzy survival curve:
Posted Image
... is of course that you can't see the the #$(&*#!! X-axis (even on the closeup), allowing one to project one's hopes into it. However, Ingram also presented the results informally at SENS1/IABG10 (6), which I was privileged to attend (psst: SENS4 is coming up -- show up for the thrill of the year!). It turns out that Metformin was one of several agents being given a very "quick"-and-dirty LS screen, and gave the clearest extension of LS: relative to the controls, there really is a significant extension of max LS, which LOOKs just like a CR curve. The bad news (wait for it!): the control group was short-lived. From my notes, written down unfortunately a week or so AFTER the event, and based on eyeballing the survival curves, the single longest-lived mouse (not max LS, which is operationally the av'g LS of the longest-lived 10%, to avoid outlier effects) of metformin vs control were 36 and 33 mo, respectively (and it might've been 33 and 30; Dr. Ingram said he'd send me a copy of the graph, but then decided he didn't want to risk violating publication embargo) ). 36 mo ~1096 days -- which is not too far from what a well-cared-for, well-nourished, non-fuckup rat lives in the lab anyway. I don't know what strain of rat this was, but eg. the AL sedentary Long-Evans rats used by Holloszy had a max LS clearly in excess of 1000 d (he doesn't give hard data in (7), but see his survival curve in Figure 2), and the max LS for F344 rats in the Biomarkers of Aging Program had max LS of: AL-F, 1072 (35.73 months); CR-F, 1292 (43.07 months); AL-M, 896 (29.87 months); CR-M, 1222 (40.73 months) (8). If they were using male F344 this might be promising -- but Ingram (and another source with close contact to his lab) confirm that there were problems with the protocol and the result can't be considered robust.

Also, there is the mortality data you mention, with the caveats you also mention: a modest superiority to other antidiabetic agents in diabetics isn't exactly an overwhelming endorsement.

Overall, I'd say metformin's merits are more "meh" than 'mazing (yes, the alliteration is an intended conceit ;) ); still, it's worth a followup -- just not a breathless one.

-Michael

References
[1] Am J Med Sci. 2008 Sep;336(3):241-7.
Effect of metformin-containing antidiabetic regimens on all-cause mortality in veterans with type 2 diabetes mellitus.
Gosmanova EO, Canada RB, Mangold TA, Rawls WN, Wall BM.
[2] Arch Intern Med. 2008 Oct 27;168(19):2070-80.
Cardiovascular outcomes in trials of oral diabetes medications: a systematic review.
Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS, Feldman L, Vassy J, Wilson R, Bass EB, Brancati FL.
Full: http://archinte.ama-...ull/168/19/2070

3. Rae MJ.
You don't need a weatherman: famines, evolution, and intervention into aging.
AGE. 2006 March;28(1):93-109.
No PMID assigned yet.

4. Rae M.
It's never too late: calorie restriction is effective in older mammals.
Rejuvenation Res. 2004 Spring;7(1):3-8. Review. No abstract available.
PMID: 15256039 [PubMed - indexed for MEDLINE]

5. Phoenix CR, de Grey AD.
A model of aging as accumulated damage matches observed mortality patterns and predicts the life-extending effects of prospective interventions.
AGE. 2007 Dec; 29(4):133-189.

6. Ingram DK.
Development of calorie restriction mimetics as a prolongevity strategy.
Biogerontology. 2003;4(Suppl 1):45(Abs81).

7. Holloszy JO.
Mortality rate and longevity of food-restricted exercising male rats: a reevaluation.
J Appl Physiol. 1997 Feb;82(2):399-403.
PMID: 9049716 [PubMed - indexed for MEDLINE]

8. Holmes DJ.
F344 Rat. Inbred Rodent Resource.
Science of Aging Knowledge Environment (SAGE KE). 2003 Sep 10;36: as2.

Edited by Michael, 10 February 2009 - 11:52 AM.


#7 AgeVivo

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Posted 09 February 2009 - 11:05 PM

I can't imagine that anyone's going to do so "@home": according to this source, which is however for breeding females (which are doubtless somewhat more expensive than non-bred females, or males), teh cost to maintain a lab mouse is "$530/year (includes cost of technician, cage washing, bedding, feed, other supplies, but not the cost of genotyping", and to get statistically significant LS results requires more than 30 animals (more than 40 would be better, and more is better still)

As you probably know i'm/we are waiting for a good choice of lifespan experiment (and time; hoping to have time starting end March) to start it at home. I was several time told -in particular when visiting Charles River- that in a large mouse facility the production cost is close to 8$/mouse/year. At home it will be more but very feasible, we would distribute the experiment (say 5 control and 5 test per person, <=10 persons) in order to distribute the costs, work and risks:
http://www.imminst.o...showtopic=21310

This "MPrize@ home" seems feasible with ad libitum studies (2 weeks of vacations isn't a trouble), potential robust life extensions (eg pool various environments to test a supplement that is known to work in SPF conditions) but not complex measurements (blood sampling and analysis) nor dietary restriction (unless we accept premature death ;) ). Michael, if you have an opinon on the choice of experiment i'm sure it will have considerable weight in our own opinions.

Edited by AgeVivo, 09 February 2009 - 11:18 PM.


#8 kismet

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Posted 30 March 2009 - 04:03 PM

Could there be a possibly increased risk of AD? Well, that would make it hardly life extending. (via a pharma blog I recently discovered)

Edited by kismet, 30 March 2009 - 04:04 PM.


#9 balance

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Posted 30 March 2009 - 04:18 PM

In the April 2009 edition of Life Extension Magazine it mentions in a review of a drug/supplement interaction book that metformin depletes folic acid by interfering with it's absorption. And goes on to state that this may explain why higher homocysteine levels are seen with long term metformin use. It says to take folic acid when taking metformin. Are you aware of this? It was the first time I heard it. I know most here are more concerned about folic acid overdose, but perhaps an easy remedy is taking a methyl-folate supplement. Kind of reminds me of the high dose pyridoxine HCL interfering with P5P.

Edited by piet3r, 30 March 2009 - 04:20 PM.


#10 krillin

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Posted 04 April 2009 - 05:56 AM

In the April 2009 edition of Life Extension Magazine it mentions in a review of a drug/supplement interaction book that metformin depletes folic acid by interfering with it's absorption. And goes on to state that this may explain why higher homocysteine levels are seen with long term metformin use. It says to take folic acid when taking metformin. Are you aware of this? It was the first time I heard it. I know most here are more concerned about folic acid overdose, but perhaps an easy remedy is taking a methyl-folate supplement. Kind of reminds me of the high dose pyridoxine HCL interfering with P5P.

It depletes B12 too.

Homocysteine also upregulates beta-secretase (BACE), so there's another mechanism besides AMPK activation.

J Alzheimers Dis. 2007 Jun;11(3):275-90.
gamma-Secretase is differentially modulated by alterations of homocysteine cycle in neuroblastoma and glioblastoma cells.
Fuso A, Cavallaro RA, Zampelli A, D'Anselmi F, Piscopo P, Confaloni A, Scarpa S.
Department of Surgery P. Valdoni, University of Rome La Sapienza, Rome, Italy.

Multiple aspects of homocysteine metabolism were studied to understand the mechanism responsible for hyperhomocysteinemia toxicity in Alzheimer disease. Besides oxidative stress and vascular damage, homocysteine has also a great importance in regulating DNA methylation through S-adenosylmethionine, the main methyl donor in eukaryotes. Alterations of S-adenosylmethionine and methylation were evidenced in Alzheimer disease and in elderly. In order to clarify whether DNA methylation can provide the basis for amyloid-beta overproduction, we used human SK-N-BE neuroblastoma and A172 glioblastoma cell lines. We tested the effects of folate, B12 and B6 deprivation and S-adenosylmethionine addition on methylation metabolism. Our results indicate that homocysteine accumulation induced through vitamin B deprivation could impair the "Methylation Potential" with consequent presenilin 1, BACE and amyloid-beta upregulation. Moreover, we found that homocysteine alterations had an effect on neuroblastoma but not on glioblastoma cells; this suggests a possible differential role of the two cell types in Alzheimer disease.

PMID: 17851177

#11 AgeVivo

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Posted 02 June 2010 - 10:58 PM

Assuming I read this (from sci.life-ex) correctly, as I skimmed some of the discussion, there was another supposed life-extension report by Roth et al from the "Symposium on Neurobiology and Neuroendocrinology of Aging", both the symposium and your post on the topic date back to 2002. I'm wondering what happened? Do you still consider their work to be legitimate? Does it merit further investigation?

I'm sorry that you only saw that post ... The study turned out to be a disappointment. Ingram et al never published the results, and the problem on that fuzzy survival curve is of course that you can't see the the #$(&*#!! X-axis (even on the closeup), allowing one to project one's hopes into it. However, Ingram also presented the results informally at SENS1/IABG10 (6), which I was privileged to attend (psst: SENS4 is coming up -- show up for the thrill of the year!). It turns out that Metformin was one of several agents being given a very "quick"-and-dirty LS screen, and gave the clearest extension of LS


Did you get more info at SENS4?
Otherwise, when looking at the closeup, I actually see that the X axis is labelled "Age [months]" (and "Months" for the graph on the left) and guess that the values are "5 6 7 8 9 10 11 12" and so on ("8 9 10 11 12 13 14 15 16"). (I you look at the closeup again you will see that it is so; or perhaps it depends on your screen config). Does it help you?

Edited by Michael, 19 February 2012 - 04:48 PM.


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#12 motorcitykid

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Posted 13 May 2011 - 07:06 PM

'Fasting Pathway' Points the Way to New Class of Diabetes Drugs

http://www.scienceda...10512132416.htm




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