10 replies to this topic

[JohnMcP]

Hi all,

I've been taking resveratrol (Res) for a couple of years in LEF
products (now about 60mg/day), and for a while I took one Longevinex
pill daily. Looking into things a bit more deeply, it seems I'm not
taking anywhere near enough. So I began a quest a couple of weeks
ago to find out two basic things: how much should I take, and where
can I get reasonably good quality Res, of verified quantity, for a
good price from a reliable seller?

Fairly quickly I ended up at the ImmInst forums, and found a _huge_
number of posts, read many of them and ended up about as confused as
I was when I started (though I did find out a lot of things I didn't
know and hadn't considered). My basic impression is that no one really
knows how much to take or even if it's effective in humans. Further,
there may be better things to take for the purpose.

I've looked around for an online FAQ summarizing at least what is
known and what are the best guesses, but those I've found so far are
too general and probably way too conservative. I didn't find one at
ImmInst (not to say that it isn't there, somewhere), but the forum
postings are way too detailed, at variance with each other, and of
course too numerous.

So now I'm back at square one, not knowing how much to take or where
to get it, which is a bit frustrating :-). I could simply order the
new 250mg capsules from LEF and take 2-3/day, but I suspect one can do
better and cheaper than that.

My guess is that I'm not the only one who wants to know these
things, so if it hasn't yet been done, I propose that a reasonably
detailed FAQ be written and maintained as new information comes in.
I'm probably not the one to do it myself, since I'm not very
knowledgable about Res and I mostly just want to find out how much
of the stuff to take :-). My bias is the pragmatic. Several other
people, however, seem keenly interested in Res, know a lot about it,
and a team effort on their part would probably be the way to go.
Best would probably be an html document on a web page somewhere,
with links to online references.

What do you think?

One thing I can help a bit with, perhaps, is coming up with some
questions. Even this is a bit tricky, because the way questions are
worded and their level of detail makes a difference in the quality of
the FAQ. So maybe that's the first thing to do, is to find the best
questions (even if it's not entirely in the spirit of "frequently
asked questions as they are usually asked").

----====ooooOoooo====----

Resveratrol FAQ, version 0.1 ;-)

0. Preliminaries:

Abbreviations:
Res = Resveratrol (3,5,4'-Trihydroxy-stilbene)
t-Res = trans-Resveratrol
c-Res = cis-Resveratrol
me-t-Res = methyl-trans-Resveratrol
ac-t-Res = acetyl-trans-Resveratrol
CR = caloric restriction

Common public references:

http://en.wikipedia....iki/Resveratrol

http://www.imminst.o...atrol-f312.html
Immortality Institute Fora on Resveratrol

http://www.imminst.o...showtopic=15059
Immortality Institute, Resveratrol - Price Watch

http://health.groups...sveratrol-users


1. What is the chemical formula for Res, and what are its various
forms?

a. I've read that Res is generally half t-Res and half c-Res.
What's the difference between them, that is, is c-Res active
at all?

b. What are the methyl and acetyl forms of Res, are they better,
and what difference do the additional groups make?


2. How does t-Res work?

a. Does t-Res exactly mimic CR, and if not, what are the key
differences?

b. How likely is it that t-Res can increase maximum lifespan in
humans, lengthening the lifespan curve, and by how much?

c. How likely is it that t-Res can increase average lifespan in
humans, squaring the lifespan curve, and by how much?

d. What other positive effects does t-Res have aside from
potentially affecting lifespan?

e. Does t-Res have any negative side-effects?


3. How likely is it that t-Res works in humans?

a. What are its effects in lower-order non-mammals? (e.g., yeast,
worm, fruit fly, fish)

b. What are its effects in small mammals, such as mice & rats?

c. What do we know about its effects in humans?


4. How much do I need to take for various effects, assuming that it
works for humans? (e.g., 5mg/kg/day to 30mg/kg/day)

a. Should I take it once daily, or spread it out through the day?

b. What forms are available, and which are probably best? (e.g.,
capsules or powder)

c. What do the purity levels (e.g., 50%, 98%, 99%) refer to, and
what are the pluses and minuses of each?

i. What is emodin, and how much of it is too much?

d. What actively decreases the bioavailability of t-Res, and how
might those factors be countered? (e.g., sulfonation,
glucuronidation, conjugation)

e. What compounds tend to counter the effects of t-Res (e.g.,
quercetin)

f. What factors, if any, increases or amplifies its
bioavailability? (e.g., micronization, solvents, synergists,
ethanol, oil, lecithin, grapefruit juice)

g. What are the alternatives to oral intake, how effective
are they in comparison, and how much t-Res is necessary for
those methods? (e.g., transdermal)


5. What are the best reliable manufacturers and distributors?

a. Which supply relatively pure t-Res, and how much do they charge?

b. Which supply relatively pure Res (50-50 mix of t-Res and c-Res),
and how much do they charge?

c. What guarantees do we have of the quality and quantitative
contents of these products?

d. What is the shelf-life of these products, which factors tend to
shorten it, and how can it be preserved or extended?

6. What other compounds have similar effects?

a. What do we know about Sirtris Pharmaceuticals products (e.g.,
SRT501), and when might they become available?


7. What are the standard, adequately peer-reviewed, references &
papers in the field?

----====ooooOoooo====----

[Anthony_Loera]

These are great questions, many of them are answered here in various forum posts, or on Wikipedia.

A FAQ should be created, and I am tempted to do so on my website to answer the questions as fairly as possible, but it may be viewed as marketing.

At this time, I think the alternative maybe to post each question separately in it's own thread, that way it is easier to search for when new people come to the forum for the question, even though the thread topic maybe "aged out" for regular members, as time passes by.

If new information comes that may further specify a response to one of the answers, a new post can be added to the "question" thread that adds more detail to the answer. What are your thoughts on this?

Anthony

Edited by Anthony_Loera, 19 March 2008 - 03:38 PM.

[drmz]

Wiki with the reference list at the bottom is a good start. Probably answers most of your questions. For additional info see the : Linus Pauling Institute

Edit: Removed quoted material for brevity.

Edited by niner, 19 March 2008 - 04:26 PM.

[niner]

A resveratrol FAQ is a great idea. We have a lot of combined expertise here, and could probably do a better job at such a FAQ than just about anyone outside of Sirtris, who probably would be loathe to do such a thing. We should do this, and put it on the front page. I'll contribute what I can.

Thanks JohnMcP for getting the ball rolling on this!

[edward]

Since many of the FAQs do not have "answers" per se only opinions, evidenced based conclusions etc. there should be a disclaimer or some statement to the effect of:

The following statements or answers reflect a summary of the collective knowledge contained in various threads on imminst.org, the conclusions from scientific studies (as interpreted by various members and registered users of imminst.org) etcetera. They are not definitive answers as many of these questions may not have "answers" or may only have incomplete answers at this time. Answers subject to speculation and conclusions based on anecdotal evidence.

[JohnMcP]

Anthony_Loera wrote:
>A FAQ should be created, and I am tempted to do so on my website to answer
>the questions as fairly as possible, but it may be viewed as marketing.

Your answers could certainly be included in the FAQ for this ImmInst forum,
and if needed they could be tagged as being the responses of a representative
of a company selling t-Res.


>I think the alternative maybe to post each question separately in it's own thread, that
>way it is easier to search for when new people come to the forum for the question

The pre-FAQ is already up to 30 questions, so each one having its own thread
would be slightly less chaotic than before, but it's still really nice to have all
the answers together in one place/post.


drmz wrote:
>Wiki with the reference list at the bottom is a good start. Probably answers most of your
>questions. For additional info see the : Linus Pauling Institute

These are good, thanks. It will take some effort to extract the info to answer the
specific questions, but it's probably easier than picking through 100's of forum posts...


niner wrote:
>A resveratrol FAQ is a great idea. We have a lot of combined expertise here, and could probably
>do a better job at such a FAQ than just about anyone outside of Sirtris, who probably would be
>loathe to do such a thing. We should do this, and put it on the front page. I'll contribute what I can.

Yes, I figured that this would be the right group of people to construct such a FAQ for the
world ... and by producing it, there's some automatic PR for ImmInst as well.
Creating the FAQ and either putting it on the front page or even just pinning it here would
make it easy to find for newcomers.


edward wrote:
>Since many of the FAQs do not have "answers" per se only opinions, evidenced based conclusions
>etc. there should be a disclaimer or some statement

Yes, that makes sense. Also tagging the replies of company reps and allowing two or more
responses per question would help make it more balanced ... or someone could create summary
answers indicating the diversity of opinion on the controversial questions.


Out of curiosity, who is working on the FAQ?
I could work on it myself, but my lack of time and detailed knowledge means that it
would probably take me several months ;-)


Onward and Upward!
John McP

http://www.facebook....?gid=2445335657
Immortality group on FaceBook

[Anthony_Loera]

I am working on some of the answers, where is this going to go on the board, in a sticky?

A

[Hedgehog]

Here is a cool little dump of SIRT1 and its function...

	1.	downregulation of Sirt1 decreases survival and increases radiation-induced antiproliferation effects of human lung cancer cells
	2.	These results support a model where the normal function of SIRT1 as a negative regulator of T cell activation is suppressed by Tat during HIV infection.
	3.	Our results indicate that nicotinamide treatment attenuates p21WAF1 expression through Sp1 downregulation, and suggest a possible involvement of nicotinamide metabolism in cellular gene expression.
	4.	Observational study of gene-disease association. (HuGE Navigator)
	5.	SIRT1 protein may be functionally associated with WRN and BLM helicases and that some major SIRT1 functions may not require its deacetylase activity.
	6.	DBC1 (deleted in breast cancer 1) acts as a native inhibitor of SIRT1 in human cells
	7.	DBC1 directly interacts with SIRT1 and inhibits SIRT1 activity in vitro and in vivo
	8.	Activation of the SIRT1/PGC-1 pathway, in a metabolic context promotes mitochondrial function and this pathway plays a role in neurodegerative disease. Review.
	9.	possible regulatory effect of SirT1 on insulin-induced tyrosine phosphorylation of IRS-2, a vital step in insulin signaling pathway, through deacetylation of IRS-2 protein.
	10.	Sirt1 exerts a protective effects against endothelial dysfunction by preventing stress-induced premature senescence.
	11.	Active regulator of SIRT1 (AROS) is the first direct SIRT1 regulator to be identified that modulates p53-mediated growth regulation.
	12.	Data show that SIRT1 is highly expressed in cancer cell lines as well as in tissue samples from colon carcinoma patients.
	13.	A novel post-translational sumoylation of SIRT1 at Lys734 increased its deacetylase activity. Stress-inducing agents promoted association of SIRT1 with SENP1 and cells depleted of SENP1 were more resistant to stress-induced apoptosis.
	14.	interaction between Sirt1 and TLE1 is important for mediating repression of NF-kappaB activity
	15.	SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention
	16.	SIRT1 promotes endothelium-dependent vascular relaxation by activating eNOS.
	17.	SIRT1 haplotypes were assessed for association with the risks of mortality, metabolic profile, age-related diseases, and cognitive functioning. These analyses revealed a trend for lower cardiovascular mortality for haplotype 2 and rs3758391 SNP carriers.
	18.	SIRT1 was distributed in cytoplasm at metaphase during mitosis, and overexpression of SIRT1 significantly augmented apoptosis for cells at metaphase.
	19.	Corepressor of androgen receptor, elucidating a new pathway relevant to prostate cancer growth and approaches to therapy.
	20.	Overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis.
	21.	provides evidence that SIRT1 activity augments apoptosis in response to TNFalpha by the ability of the deacetylase to inhibit the transactivation potential of the RelA/p65 protein
	22.	Data show that physiological concentrations of nicotinamide noncompetitively inhibit SIRT1 in vitro.
	23.	FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1
	24.	evidence for an androgen receptor (AR) regulatory pathway controlled by SIRT1; SIRT1 antagonists induce endogenous AR expression and enhance dihydrotestosterone-mediated AR expression
	25.	SIRT1 represses forkhead transcription factors and reduces apoptosis
	26.	SIRT1 is significantly elevated in mouse and human prostate cancer
	27.	SIRT1 is a histone H3/H4 deacetylase in mammalian cells and in transcriptional repression mediated by CTIP2
	28.	Hiv Tat is deacetylated by human sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein deacetylase in vitro and in vivo
	29.	expression of SIRT1 in the brain resulted in decreased ROCK1 expression and elevated alpha-secretase activity; SIRT1 activation in the brain is a novel mechanism through which calorie restriction may influence Alzheimer disease amyloid neuropathology
	30.	SIRT1 and FOXO3 formed a complex in cells in response to oxidative stress; SIRT1 deacetylated FOXO3; SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death
	31.	These results indicate that the molecular association between HES1-, HEY2- and SIRT1-related proteins is conserved among metazoans, from Drosophila to human, and suggest that the Sir2-bHLH interaction also plays important roles in human cells.
	32.	Data describe the cloning, chromosomal characterization and mapping of the NAD-dependent histone deacetylases gene sirtuin 1.(
	33.	binding of resveratrol to SIRT1 promotes a conformational change that accommodates the attached coumarin group
	34.	The association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.
	35.	propose that the reduction in transcriptional repression mediated by hypermethylated in cancer 1, due to the decrease of CtBP binding, increases SIRT1 expression
	36.	SIRT1 deacetylation and repression of p300 involves specific lysine residues in the cell cycle regulatory domain 1
	37.	histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications regulate MEF2
	38.	Although SIRT1 deacetylates p53, this does not play a role in cell survival following DNA damage in certain cell lines and primary human mammary epithelial cells.
	39.	AIF-mediated cell death is regulated by the functional interplay of SIRT1 and PARP-1 in response to DNA damage
	40.	substrate recognition by SIRT1 does not depend on the amino acid sequence proximate to the acetylated lysine
	41.	SIRT1 has a role in transcriptional repression mediated by BCL11A in mammalian cells
	42.	the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence
	43.	SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling
	44.	Overexpression of sirt1 induced expression of P-glycoprotein and rendered cancer cells resistant to doxorubicin.
	45.	These data show that SIRT1 regulates cigarette smoke-mediated proinflammatory mediator release via NF-kappaB, implicating a role of SIRT1 in sustained inflammation and aging of the lungs.
	46.	There is a mutual regulation between E2F1 and SirT1 that affects cellular sensitivity to DNA damage.
	47.	SIRT1 can modulate p73 activity via deacetylation.
	48.	In contrast, a SIRT1 inhibitory compound showed a stimulatory activity on the differentiation of adipocytes, a feature often linked to insulin sensitization.
	49.	HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes.
	50.	Deacetylation of NBS1 by SIRT1 plays a key role in the dynamic regulation of the DNA damage response and in the maintenance of genomic stability.
	51.	Data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan.
	52.	PARP activation and the concomitant reduction of Sir2alpha activity in failing hearts regulate the post-translational acetylation of p53
	53.	HIC1 is a target of the class III deacetylase SIRT1 and identify a new posttranslational modification step in the P53-HIC1-SIRT1 regulatory loop.
	54.	SIRT1 modulates DNA repair activity, which could be regulated by the acetylation status of repair protein Ku70 following DNA damage
	55.	SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death
	56.	SIRT1 regulates cigarette smoke induced pro-inflammatory mediators release via RelA/p65 NF-{kappa}B in macrophages.
	57.	SIRT1(Sir2alpha) deacetylates p53 and promotes survival

Edited by Hedgehog, 16 April 2008 - 07:33 PM.

[Anthony_Loera]

nice!

[Hedgehog]

nice!

Should be easier to find specific articles with something like that....

[Hedgehog]

Resveratrol: One molecule, many targets

Abstract

Resveratrol is one of the numerous polyphenolic compounds found in several vegetal sources. In recent years, the interest in this molecule has increased exponentially following the major findings that resveratrol (i) is shown to be chemopreventive in some cancer models, (ii) is cardioprotective, and (iii) has positive effects on several aspects of metabolism, leading to increased lifespan in all the metazoan models tested thus far, including small mammals. Such remarkable properties have elicited a vast interest towards the identification of target proteins of resveratrol and have led to the identification of enzymes inhibited by resveratrol and others whose activation is enhanced. In the vast majority of cases, resveratrol displays inhibitory/activatory effects in the micromolar range, which is potentially attainable pharmacologically, although targets with affinities in the nanomolar range have also been reported. Here, we provide an overview of the various classes of enzymes known to be inhibited (or activated) by resveratrol. It appears that resveratrol, as a pharmacological agent, has a wide spectrum of targets. The biological activities of resveratrol may thus be dependent on its simultaneous activity on multiple molecular targets. © 2008 IUBMB IUBMB Life, 60(5): 323-332, 2008Received: 16 November 2007; Accepted: 8 January 2008

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