Suggestions for mouse lifespan studies
spin...@gmail.com
Does anyone have suggestions of single or groups of supplements, food
additives or drugs to test in mouse lifespan studies?
I have funding for such studies. If you do, please forward your
suggestions to me at spin...@gmail.com. Please include some
information about the rationale for the suggestions.
I am already aware of and considering the following:
ALT-711
Metformin
Torcetrapib
Acipimox
Metoprolol
NAP
Teriparatide
cgk733
srt501
Desferrioxamine
fisetin
lipoic acid [We tested this at 600 mg/kilogram of the control diet
alone and with n-acetyl-l-cysteine (2000) & vitamin E (585) & lycopene
(300) and found no effect]
propyl gallate
Trolox
Tocopherol monoglucoside (TMG), a water soluble derivative of vitamin
E
Ascorbyl palmitate (PROBABLY NOT SUITABLE)
Taxifolin
LY294002
Chenodiol (kee-noe-DYE-ole) (a.k.a. chenodeoxycholic acid)
Loxapine succinate
synthetic beta-amino acid proteins
buckyball c60 antioxidants
EUK antioxidant compounds
statins
resveratrol derivatives
lithium
anti-convulsants
dichloroacetate
rapamycin
pineal hormones. 5 in all.
cortagen, epithalon, vilon, livagen, prostamax other short synthetic
peptides.
ACE inhibitors
Januvia (Merck) (a.k.a. LAF237)
Exenatide (a.k.a. Exendin-4, marketed as Byetta) (Amylin
Pharmaceuticals, Inc. and Eli Lilly and Company)
Lipoxygenase Inhibitors
AICAR
Go6976
Imatinib (a.k.a. Gleevec, Imatinib Mesylate, STI571, CGP57148B)
Inhibitors of PDGF receptor
Gefitinib
Erlotinib
AG1024
Cetuximab
PhGalpha
Enzastaurin
Arxxant (ruboxistaurin)
KAI-9803
PKC412
mannoheptulose
phenyl isopropyl adenosine
phlorizin
bitter melon
And the NIA interventions testing program is already testing:
Aspirin
4-OH-PBN
NFP
NDGA
Enalapril
CAPE high
CAPE low
Rapamycin
Simvastatin high
Simvastatin low
Resveratrol high
Resveratrol low
Thanks ,
Steve Spindler
Stephen R. Spindler, Ph.D.
Professor
Department of Biochemistry
University of California, Riverside
Riverside CA 92521
http://www.biochemistry.ucr.edu/faculty/spindler.html
njnava...@yahoo.com
input? That's GREAT news!
Ok, here are my suggestions. I suggest that the following be given as
a group. But don't get carried away with the dosages. Since funds are
no doubt limited, if there is not enough money for a range of dosages,
go with low to moderate dosages.
1) Grape Seed Extract (say, "Activin" brand)
2) L-Arginine
3) Magnesium Citrate
4) Niacin and/or N-Ribosylnicotinamide & Methyl Donor such as Betaine
and/or Lecithin
5) Orange Peel Extract - including Nobiletin, Tangeretin, etc.
6) Fat soluble vitamin complex including D & A & K2
On Jul 9, 4:10 pm, spindl...@gmail.com wrote:
> Dear list members,
>
> Does anyone have suggestions of single or groups of supplements, food
> additives or drugs to test in mouse lifespan studies?
>
> I have funding for such studies. If you do, please forward your
> suggestions to me at spindl...@gmail.com. Please include some
betai...@yahoo.com
high dose biotin
a comparison of high dose folic acid to high dose metafolin aka
folinic acid
both of the above combined with betaine
An improved version of Bruce Ames's work with r-alpha lipoc acid
and carnitine (in various forms). As I recall his work left some
issues open. And begged I thought for additional animal model
as well.
All the "old" radioprotectants that can be used long term.
Much of this work was done in the 1960's or 70's.
niacin in combination of betaine.
I'd start with trials on likely combinations rather than
single substance trials.
High dose forms of ubiquinone and ubiquinol and related analogs
And I'd keep an eye on stress proteins....ubiquitins
In male models for idealizing the death curve, I'd consider
a range of a number of anabolic steriods. One almost
comes to mind, it was used to salvage test animals
after LD 50/50 gamma ray exposure as I dimly recall.
And what I'll call a "Michael Price" style regimen of B-vitamins.
Do a Google search of the groups archive for that.
Also and I think this may have been covered, those chemicals/drugs/
nutrients that help regulated blood sugar levels could be
useful.
------------------------------------------------
Then there would be the more technically challenging things:
Such as somehow placing mitochondrion of long lived birds or whales
into
mice or other short lived animal models.
And assorted mxing and matching of genes from short and long lived
species.
mwes...@ic.edu
would love to see tested in a lifespan study:
1. pterostilbene (you may already be thinking of this as a resveratrol
analog)
2. niacinamide--is it really the "anti-resveratrol"? I'm guessing
mammals won't respond to this as yeast do, but I'm just guessing.
3. gamma tocopherol--since it has become the fall-back position of the
E advocates that this is significantly more effective than alpha,
let's test it!
4. B6 and pantothenic acid--these have old, unreplicated positive
studies that should be replicated.
5. chromium picolinate--everyone seems to have relegated the early
Evans lifespan study to the "well, that's just stupid" file, but it
continues to intrigue me. It certainly improves my insulin and blood
sugar metabolism. If it only works for those of us with marginal
blood sugar regulation and has no effect on normal rodents, it would
certainly be nice to know.
Good luck with your research!
Mike Westbrook
mwes...@ic.edu
gulping this stuff in large quantities on what seems like very limited
evidence to me. Since there seems to be some evidence for hormetic
effects from AGEs one wonders whether benfo will prove beneficial on
balance.
The longevist set also seems enamored of ashwagandha and bacopa these
days, as well as rhodiola and maca. It would be interesting to see
what these "adaptogenic" herbs can actually do.
And finally, let me second Nelson's suggestion of OPCs from grape
seed. Grape seed extract seems like an unsung superstar to me, well
deserving of a close look.
Mike
Mike O'Gara
I'd like to see the addition of NtBHA.
I see you've already listed a variant of PBN, but NtBHA appears to be the
good/active portion of PBN.
Supporting info sent via email.
-- Mike O'Gara
njnava...@yahoo.com
> I'll suggest the following in addition:
>
> high dose biotin
What makes you say that? Do you have any evidence to back it up?
>
> a comparison of high dose folic acid to high dose metafolin aka
> folinic acid
> both of the above combined with betaine
Huh? What evidence do you have for any of these suggestions? AFAIK,
provided the subject is not "deficient", folic acid acid has been
shown to have no positive effect on risk of all-cause mortality.
>
> An improved version of Bruce Ames's work with r-alpha lipoc acid
> and carnitine (in various forms). As I recall his work left some
> issues open. And begged I thought for additional animal model
> as well.
Oh no...not lipoic acid again...
>
> All the "old" radioprotectants that can be used long term.
> Much of this work was done in the 1960's or 70's.
I would guess he's interested in specific compounds, with some
evidence in support, rather than vague generalizations. Assuming he
doesn't have an unlimited supply of money to test everything under the
sun, what makes you think "radioprotectants" are generally good anti-
aging candidates? For example vitamin E is "radioprotective" (PMID
11873518) yet it may actually increase risk of all-cause mortality
well before you even get to effective radioprotective dosages (PMID
15537682).
>
> niacin in combination of betaine.
I've already mentioned that.
>
> I'd start with trials on likely combinations rather than
> single substance trials.
>
> High dose forms of ubiquinone and ubiquinol and related analogs
I wonder how many times CoQ-10 has to be tested before people will
accept the fact that it does nothing for life span?
>
> And I'd keep an eye on stress proteins....ubiquitins
There are lots of things to "keep an eye on". The question is: which
specific things would you test (assuming a finite amount of money)?
>
> In male models for idealizing the death curve, I'd consider
> a range of a number of anabolic steriods. One almost
> comes to mind, it was used to salvage test animals
> after LD 50/50 gamma ray exposure as I dimly recall.
>
> And what I'll call a "Michael Price" style regimen of B-vitamins.
> Do a Google search of the groups archive for that.
LOL! I can't believe you're telling him to Google search for "Michael
Price"!
Curious
please consider including a test combining Resveratrol and Oxaloacetic
Acid. Resveratrol already is well know. Oxaloacetic is thought to
improve nad+/nadh ratio acid may be synergistic to Resveratrol and this
is one thing i'd love to see tested.
Oxaloacetic Acid is easily available. Contact for further information i
suggest Alan Cash ( ac...@ix.netcom.com )
To quote Mr Cash
"
On combining benaGene with resveratrol, we do not know if it has any
benefit. One of the reasons for this lack of knowledge is the difficulty
in detecting what resveratrol does in the body. As we understand it at
this point (and subject to change at any point in time), resveratrol
increases the rate that the Sirt1 protein reacts with it's substrate
(affecting the Km), but does not necessarily increase either the
transcription rate of the protein from the gene, nor the amount of
protein in the cells. Thus, the effects are difficult to measure.
We have blocked the effect of the sir2 gene in worms with a compound
call Splitomycin, and also fed them benaGene. The worms continued to
live longer than the control group, but not as long as worms without the
splitomycin. So there is a decrease when the sir2 gene is blocked, but
only about a 1/3 decrease in the excess lifespan, indicating other genes
are involved in the extension (at least in worms). There is also some
controversy if Splitomycin is a good blocker for the sir2 gene, so we
are looking closer at our results.
...
Regards,
Alan Cash
Terra Biological LLC
ac...@ix.netcom.com
"
and also i quote Mr Cash
"
"Your proposal to the NIA Interventions Testing Program (ITP) has been
reviewed through a two-tier review and prioritization process, and was
given a high priority for inclusion in the next round of testing."
NIA/NIH has some additional questions that we have to answer before we
will know if benaGene is fully accepted into the program. It looks good
so far....we should know in a month or so. It will generate quite a bit
of data.
More on the Intervention Testing Program can be found at the following
web site: http://www.nia.nih.gov/ResearchInformation...tingProgram.htm
Most of our work will not be published because it deals with efficacy,
stability and toxicity that was required in the permitting process. We
do not wish to share this information with competitors at this time--we
think parts of our blend will go generic soon enough without providing
the information to our competitors.
Our work on life extension in animals should be reported within the next
six months. So a good question is, "Why is benaGene being offered now?
Why not wait six months?"
Once the product became legal to sell, we had a moral decision. Wait for
the publications, or offer it for sale immediately. There was quite a
bit of internal heated debate over this, and, as per most debates, both
sides were right. We decided to offer benaGene for sale now, because the
toxicity data indicates that it has about the same toxicity as a lemon
(as would be expected from a Krebs cycle metabolite), and it may do
significant good.....
Some other papers to consider:
Puntel, RL et al, "Krebs Cycle Intermediates Modulate Thiobarbituric
Acid Reactive Species (TBARS) Production in Rat Brain In Vitro",
Neurochemical Research, Vol. 30, No. 2 February 2005 pp. 225-235
Wood, JP et al, "Zinc and Energy Requirements in Induction of Oxidative
Stress to Retinal Pigmented Epithelial Cells", Neurochemical Research,
Vol. 28, No. 10, October 2003, pp. 1525-1533
Yamamoto, H, et al, "Effect of alpha-ketoglutarate and oxaloacetate on
brain mitochondrial DNA damage and seizures induced by kainic acid in
mice" Toxicology Letters, 143 (2003) pp. 115-122
Desagher, S, et al, "Pyruvate Protects Neurons against Hydrogen
Peroxide-Induced Toxicity", The Journal of Neuroscience, December 1,
1997 pp 9060-9067
"
I hope this suggestion is of some interest to you and helps in some way.
Regards
--
"I don't wanna die, there's no future in it!"
~Curly Howard
dean...@yahoo.com
> Dear list members,
>
> Does anyone have suggestions of single or groups of supplements, food
> additives or drugs to test in mouse lifespan studies?
>
> I have funding for such studies. If you do, please forward your
Dear Dr Spindler:
I am engaged in the practice of Rehabilitation and Physical Medicine.
Nutritional and Biochemical
agents to support and accelerate tissue and nerve repair, while
enhancing and extending
neural function has been a particular area of interest and study for
me. Several compounds that
may be of interest in mouse lifespan studies, are: Glycine Agonists
[Magnesium Glycinate,
Glycinamide], Demanyl Phosphate, Lazaroids [Tirilazad], and one very
old drug which has
had a lot of controversy surrounding it, ACS Serum [Antireticular
Cytotoxic Serum--this is
still marketed as 'Serocytol', and I have had personal experience with
this agent, as an effective
immunostimulant [the company manufacturing this suggests that it has a
non-specific
tissue-regenerating action].
Regards,
Dr. Dean Benson
Bolsa Harbour Physical Medicine
christophe...@gmail.com
>
> Does anyone have suggestions of single or groups of supplements, food
> additives or drugs to test in mouse lifespan studies?
>
> I have funding for such studies. If you do, please forward your
Hydroxychloroquine
Silymarin
TA-65/ astragalus
D.
I read about a trial that Swedish Herbal Institute did in Europe with
their unique Rhodiola extract (SHR-5) and a sea slug variety. They
subjected the sea slugs to a variety of toxin baths and those which
had been eating Rhodiola lived and reproduced. Those that had not been
eating Rhodiola had either expired or could not reproduce. This kind
of protective effect may transfer to the rodents as well, and
hopefully to humans!
I can dig up a PDF of this peer-reviewed research paper if anyone
would like a copy, they can send me a private email. Or, if a US lab
is working in this field and they want a source of SHR-5, please write
me directly as well.
regards,
Dave
On Jul 10, 8:51 am, "mwest...@ic.edu" <mwest...@ic.edu> wrote:
> One that I can't believe I forgot: benfotiamine! Longevists are
> gulping this stuff in large quantities on what seems like very limited
> evidence to me. Since there seems to be some evidence for hormetic
> effects from AGEs one wonders whether benfo will prove beneficial on
> balance.
>
> The longevist set also seems enamored of ashwagandha and bacopa these
> days, as well asrhodiolaand maca. It would be interesting to see
RArmant
crystalline form as Teavigo.
RArmant
>6) Fat soluble vitamin complex including D & A & K2
The problem with vitamin D is that mice probably do not have
to little because they have evolved other ways to get their
vitamin D than Sun exposure. Otoh, we humans dependent on Sun
exposure to get our vitamin D and nowadays wear clothes causing
a D deficiency.
physic...@gmail.com
extends the life span of Drosophila:
Life extension in Drosophila by feeding a drug
Hyung-Lyun Kang, Seymour Benzer, and Kyung-Tai Min
Proc Natl Acad Sci USA. 2002 January 22; 99(2): 838-843.
pj
betai...@yahoo.com
> > I'll suggest the following in addition:
> > high dose biotin
> What makes you say that? Do you have any evidence to back it up?
Oh maybe here is bit of. Just that it is needed for the histones and
to help
handle glucose management and blood lipids. And I see diabetes
as speeding certain aspects of aging.
Also see PMID: 16102804 PMID: 15231238
I had more but the computer rebooted.
I will say this is a topic I currently trying to
sort out in my mind. But the above reasoning
was enough to get me to bump my dose.
> > a comparison of high dose folic acid to high dose metafolin aka
> > folinic acid
> > both of the above combined with betaine
> Huh? What evidence do you have for any of these suggestions? AFAIK,
> provided the subject is not "deficient", folic acid acid has been
> shown to have no positive effect on risk of all-cause mortality.
Some memebers of northern European populations don't handle folic acid
well. I suppose
some of the test mice would need a model strain of animal. In
research,
I think the goal is to find something interesting and useful.
If I were researcher if I found a way to lower a specific cause of
mortality I'd be happy. In humans some may need only 700 mcgs
per day for optimal genomic stability but others may need 4000 mcgs.
This may not increase the species maximum lifespan but it might
extend an individual's span toward the species maximum. Or at
least help sort out whether the homocysteine is marker or a cause of
disease.
> > An improved version of Bruce Ames's work with r-alpha lipoc acid
> > and carnitine (in various forms). As I recall his work left some
> > issues open. And begged I thought for additional animal model
> > as well.
> Oh no...not lipoic acid again...
Ames did seem find benefits with it and carnitine.
But his work had some holes in it
as I recall.
Perhaps you have an idea as what else to take
instead of r-alpha-lipoic acid when taking carnitine?
> > All the "old" radioprotectants that can be used long term.
> > Much of this work was done in the 1960's or 70 would guess
> he's interested in specific compounds, with some
> evidence in support, rather than vague generalizations. Assuming he
> doesn't have an unlimited supply of money to test everything under the
> sun, what makes you think "radioprotectants" are generally good anti-
> aging candidates? For example vitamin E is "radioprotective" (PMID
> 11873518) yet it may actually increase risk of all-cause mortality
> well before you even get to effective radioprotective dosages (PMID
> 15537682).
================================
OK, I meant just about anything with a thiol functional group;-)
Cysteamine PMID: 9247075
N-(carboxy)-beta-alanyl-cysteamine PMID: 7923208
5-androstenediol
symmetrically and unsymmetrically N,N'-diaryl-substituted
amidinomethyl diethyldithiocarbamates PMID: 3031292
And while we are mentioning vitamin E, perhaps tocotrienols?
In the late 1950's radiation exposure was seen a model
of aging. I was recycling.
>> niacin in combination of betaine.
> I've already mentioned that.
Fair enough. This posting wasn't one my finest moments.
Betaine and niacin are nutrients I use in rather large doses.
Betaine HCL with pepsin to prevent my dyspepsia and reflux.
And the high dose niacin helps to lessen ankle pain with time
and additional betaine HCL or betaine
base to helps prevent the niacin flush.
> > I'd start with trials on likely combinations rather than
>> single substance trials.
> > High dose forms of ubiquinone and ubiquinol and related analogs
> I wonder how many times CoQ-10 has to be tested before people will
> accept the fact that it does nothing for life span?
Really, it may prevent or slow the progression of
neurodegenerative disorders such as Parkinson's disease.
If one avoids the various cancers, CVD and amyloid deposits, I'd
think
neurodegenerative disorders would be up there
in causes of death as the death curve becomes more squared.
Anyway most of what is currently called life extension is
in fact curve squaring at least in theory.
Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1
mice
PMID: 16387461
Enhanced anti-oxidant protection of liver membranes in long-lived
rats
fed on a coenzyme Q10-supplemented diet.
PMID: 16125350
MitoQ counteracts telomere shortening and elongates lifespan
of fibroblasts under mild oxidative stress.
PMID: 12882327
But as you say it flops when it comes to a healthy strain of mice
for the purposes of a longer lifespan.
The effects of lifelong ubiquinone Q10 supplementation on the
Q9 and Q10 tissue concentrations and life span of male rats and mice.
(no benefit to lifespan)
PMID: 9584986
> >And what I'll call a "Michael Price" style regimen of B-vitamins.
> >Do a Google search of the groups archive for that.
> LOL! I can't believe you're telling him to Google search for "Michael Price"
I have not seen him post recently. The last time I noticed his web
presence,
he tried a posting to Paul Wakfer's Morelife Yahoo group.
He was always one for huge doses of B vitamins. The point intended
was to use a broad regimen like used by most(?) denizens of this
forum
to one degree or another as opposed to a single chemical intervention.
I take it you and Price had a disagreement? Personally I like
some disagreement as I forces me (I hope) to improve
my grasp of a topic.
=================================================================
"Most of the resources available under the rubric "aging research"
are not used for that purpose at all," Hayflick
PMID: 15215267
Paul Antonik Wakfer
>
> Does anyone have suggestions of single or groups of supplements, food
> additives or drugs to test in mouse lifespan studies?
>
> I have funding for such studies. If you do, please forward your
> information about the rationale for the suggestions.
[snipped items already under consideration]
Hi Steve,
It is good to see that you have more funding for mouse lifespan
studies.
In addition to many on your list, I would place the following high on
the list.
Astragaloside IV
(see Geron's patent and all the hoppla about TA65)
Pyridoxamine dihydrochloride
see my review page at: http://morelife.org/supplements/PM.html
(-)-BPAP aka: R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane
see my review page at: http://morelife.org/researchems/BPAP.html
N-acetyl-L-carnosine
see my review page at: http://morelife.org/supplements/NALC.html
I also agree with some of the other suggestions, particularly NtBHA
see my review page at: http://morelife.org/researchems/NtBHA.html
By the way, for animal research purposes I can supply highly pure
powders of all of the above (excluding Astragaloside IV) and also of
axcipimox EUK-189 and ALT-711 which are already on your list.
I currently take all of these chemicals daily (and many more).
Question: IMO, aminoguanidine hydrochloride is also an obvious
candidate. Why is it not on the list?
--Paul Wakfer
MoreLife for the rational - http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project - http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting
timo...@my-deja.com
multiflori.
Research on this substance, mostly by the Chinese, indicate it has an
anti-aging effect like resveratrol and curcumin. Fo ti which contains
emodin has a historical reputation as a longevity agent in China. I
think it may have already been tested (polygonum multiflorii chickens
or quail and significantly increased longevity. If lipoic acid is
tested it would seem to me prudent to include biotin with it as LA may
cause a deficiency in biotin...which may have had an affect in earlier
tests.
Tim
Pierre-Alain Gouanvic
I would suggest organic germanium (carboxyethylgermanium sesquioxide).
This trace element is clearly underresearched.
Its effect seem to be broad, impressive (cardiovascular, anticancer,
neurological...). I perceive it as an essential nutrient not yet
recognized as such, which functions aren't yet known because we don't
yet know how to look at it. What enzymes or molecules does it work
with, and how? Does it behave strangely, at the subatomic level?
I'd also like to see some research made on the physico-chemical basis
of acupuncture's effects, which are now amply demonstrated by fMRI.
Some believe that nitric oxide might be involved. I'd say that free
radical-centered perspectives should perhaps be looked at from this
point of view.
But my practical advice for now is : germanium.
Good luck!
Pierre-Alain Gouanvic