Vitamin C 'Cures' Mice With Accelerated Aging Disease
rs1...@yahoo.com
Thomas Carter
> http://www.sciencedaily.com/releases/2010/01/100104101210.htm
Hi RS,
Potentially very important, I'm guessing it will take very hi doses to
help normal people with short telomeres. I've seen a lot of in vitro
data that C might well maintain telomeric length, and of course
Werner's is a disease of short telomeres. Some abs below, folowing
the article.
Thomas
Public release date: 4-Jan-2010
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Contact: Cody Mooneyhan
cmoon...@faseb.org
301-634-7104
Federation of American Societies for Experimental Biology
New year, new vitamin C discovery: It 'cures' mice with accelerated
aging disease
New research in the FASEB Journal reports vitamin C reverses
abnormalities caused by Werner syndrome gene, including cancer,
obesity, diabetes, heart failure and high cholesterol
A new research discovery published in the January 2010 print issue of
the FASEB Journal (http://www.fasebj.org) suggests that treatments for
disorders that cause accelerated aging, particularly Werner's
syndrome, might come straight from the family medicine chest. In the
research report, a team of Canadian scientists show that vitamin C
stops and even reverses accelerated aging in a mouse model of Werner's
syndrome, but the discovery may also be applicable to other progeroid
syndromes. People with Werner's syndrome begin to show signs of
accelerated aging in their 20s and develop age-related diseases and
generally die before the age of 50.
"Our study clearly indicates that a healthy organism or individuals
with no health problems do not require a large amount of vitamin C in
order to increase their lifespan, especially if they have a balanced
diet and they exercise," said Michel Lebel, Ph.D., co-author of the
study from the Centre de Recherche en Cancerologie in Quebec, Canada.
"An organism or individual with a mutation in the WRN gene or any gene
affected by the WRN protein, and thus predisposes them to several age-
related diseases, may benefit from a diet with the appropriate amount
of vitamin C."
Scientists treated both normal mice and mice with a mutation in the
gene responsible for Werner's syndrome (WRN gene) with vitamin C in
drinking water. Before treatment, the mice with a mutated WRN gene
were fat, diabetic, and developing heart disease and cancer. After
treatment, the mutant mice were as healthy as the normal mice and
lived a normal lifespan. Vitamin C also improved how the mice stored
and burned fat, decreased tissue inflammation and decreased oxidative
stress in the WRN mice. The healthy mice did not appear to benefit
from vitamin C.
"Vitamin C has become one of the most misunderstood substances in our
medicine cabinets and food," said Gerald Weissmann, M.D., Editor-in-
Chief of the FASEB Journal. "This study and others like it help
explain how and why this chemical can help to defend some, but
certainly not all, people from premature senescence."
A new report in the journal Life Sciences, volume 63, 1998, by Dr.
Kayo Furumoto reported that age-dependent telomere shortening which
occurs in human cells was slowed down by vitamin C. ( Below is the
abstract of the study which shows that only ascorbate with two
phosphorus atoms causes the slow down of 45% because it increases
intracellular ascorbic acid and regular ascorbic acid does not.
Age-dependent telomere shortening is slowed down by enrichment of
intracellular vitamin C via suppression of oxidative stress.
Furumoto K, Inoue E, Nagao N, Hiyama E, Miwa N
Department of Cell Biochemistry, Hiroshima Prefectural University
School of BioSciences, Shobara, Japan.
Telomeres in eukaryotic somatic cells are destined to the age-
dependent shortening, which has not been demonstrated to correlate to
direct lesion of telomeric DNA by reactive oxygen intermediates (ROI);
still less explicable is the inhibitory effect of ROI-scavenging on
telomere shortening. Here, we succeeded in artificial slowdown of age-
dependent telomere shortening to 52-62% of the untreated control, in
human vascular endothelial cells, by addition of the oxidation-
resistant type of ascorbic acid (Asc), Asc-2-O-phosphate (Asc2P),
which concurrently achieved both extension of cellular life-span and
prevention of cell size enlargement indicative of cellular senescence.
The results are attributable to a 3.9-fold more marked enrichment of
intracellular Asc (Asc(in)) by addition of Asc2P, subsequently
dephosphorylated before or during transmembrane influx, than by
addition of Asc itself, and also attributed to diminution of
intracellular ROI to 53% of the control level by Asc2P; telomerase
activity was at a trace level and underwent an age-dependent decline,
which was significantly decelerated by Asc2P. Thus, age-dependent
telomere-shortening can be decelerated by suppression of intracellular
oxidative stress and/or by telomerase retention, both of which are
achieved by enriched Asc(in) but not by extracellular Asc
overwhelmingly more abundant than Asc(in).
PMID: 9747894, UI: 98418690
Nippon Rinsho 1999 Oct;57(10):2223-9 [Vitamin C: structure-activity
correlation and cytoprotective actions through free radical scavenging
and extracellular matrix construction] [Article in Japanese] Kaneko K,
Nagao N, Miwa N. Department of BioTechnology, Hiroshima Prefectural
University School of BioSciences. Conventional studies on
vitamin C have been conducted by single-dosage administration with
ascorbic acid itself being so labile as to undergo irreversible
degradation. In contrast, enrichment of intracellular ascorbate is
accomplished by pro-vitamin C in which its 2,3-enediol moiety is
protected with phosphate ester, being thereafter enzymatically
esterolyzed. Ascorbic acid-2-O-phosphate (Asc2P) gradually releases
ascorbate, which is cumulatively taken up into diverse human or
mammalian cells, and prevents cell injuries such as post-ischemic
reperfusional injury in the liver or heart, age-dependent telomeric
DNA shortening in endothelial or epithelial cells, UV-B irradiational
injury in the skin and lipid peroxide-induced injury in the vascular
endothelium, and tumor invasion and metastasis. Publication Types:
Review Review Literature PMID: 10540866......................;[These
two from the telomer section suggest Werner's syndrom is caused by
short telomeres.].............................
J Cell Sci. 2007 Mar 1;120(Pt 5):713-21.Related Articles, Links
WRN at telomeres: implications for aging and cancer.
Multani AS, Chang S.
Department of Molecular Genetics, U.T. M.D. Anderson Cancer Center,
Houston, TX 77030, USA.
Werner Syndrome (WS) is a premature aging
syndrome characterized by early onset of age-related pathologies and
cancer. Since WS is due to a single gene defect, it has attracted much
interest from researchers seeking to understand pathways that
contribute to cancer and aging at cellular and molecular levels. The
protein mutated in WS, WRN, appears to play a major role in genome
stability, particularly during DNA replication and telomere
metabolism. Much of the pathophysiology associated with WS, including
the rapid onset of cellular senescence, early cancer onset and
premature aging, can be attributed to a defect in telomere
maintenance. Recent genetic evidence from the mTerc(-/-) Wrn(-/-)
mouse demonstrates that mice with critically shortened telomeres
display aging phenotypes reminiscent of human WS, further reinforcing
the notion that telomere dysfunction is required for the manifestation
of aging pathophysiologies in the setting of WRN deficiency. PMID:
17314245
6: Mol Cell Biol. 2008 Mar;28(6):1892-904. Epub 2008 Jan 22.Related
Articles, Links
WRN controls formation of extrachromosomal telomeric circles and is
required for TRF2DeltaB-mediated telomere shortening.
Li B, Jog SP, Reddy S, Comai L.
Department of Molecular Microbiology and Immunology, Institute for
Genetic Medicine, Keck School of Medicine, University of Southern
California, 2250 Alcazar St., CSC 264, Los Angeles, CA 90033, USA.
Telomere dysfunction has been proposed to contribute
to the pathogenesis of Werner syndrome (WS), a premature-aging
disorder. The WS protein WRN binds TRF2, a telomere-specific factor
that protects chromosome ends. TRF2 possesses an amino-terminal domain
that plays an essential role in preventing telomere shortening, as
expression of TRF2(DeltaB), which lacks this domain, leads to the
formation of telomeric circles, telomere shortening, and cell
senescence. Our data show that the TRF2(DeltaB)-induced telomeric-loop
homologous-recombination pathway requires WRN helicase. In addition,
we show that WRN represses the formation of spontaneous telomeric
circles, as demonstrated by the increased levels of telomeric circles
observed in telomerase-positive WS fibroblasts. The mechanism of
circle formation in WS cells does not involve XRCC3 function. Circle
formation in WS cells is reduced by reconstitution with wild-type WRN
but not mutant forms lacking either exonuclease or helicase activity,
demonstrating that both enzymatic activities of WRN are required to
suppress telomeric-circle formation in normal cells expressing
telomerase reverse transcriptase. Thus, WRN has a key protective
function at telomeres which influences telomere topology and inhibits
accelerated attrition of telomeres.
PMID: 18212065
jw
market; AFAIK, it's not the same as "Ester C". Does anyone know
about its availability?
Paul Antonik Wakfer
No, it bears no relationship nor has the same properties as Ester C.
It gets into the cell unchanged precisely because of its
phosphorylated nature (many chemicals are phosphorylated and
dephosphorylated - usually by hydrolysis - as they go into and out of
cells, respectively - which is why it is largely a waste of money to
pay extra for phosphorylated vitamins).
The importance of Asc2P was already quite clear several years ago and
I searched for it then without success. The latest research shows it
to be even more clearly very important (as Thomas indicated) and I
have searched again. All that I find are Chinese companies wanting to
sell minimum quantities of 25 kg or more (some a minimum of a metric
ton!). It will undoubtedly be available at chemical supply houses, but
is at none which I have dealt with recently and will take an order
from me without a big hassle (caused by government regs, of course).
In addition, such chemical supply companies generally charge very high
prices for quite small quantities of pure chemicals because most
research funded by government grants is willing and able to pay those
prices. It is only us second class commoners who pay for those grants
through our stolen tax money that get shafted by this arrangement and
the State does not care about that.
Whether it can be sold legally by supplement companies I do not know,
but I sure wish that one of them would try making it available.
--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
Pramesh Rutaji
I suspect a directed "reverse" marketing campaign where we target one
particular supplement supplier and make regular and numerous requests
that they add the option to their line up might work?
--
Pramesh Rutaji
p297ton...@newsguy.com - remove tongue to reply
Thomas Carter
Hi,
I researched this issue some time ago, and the following is from
memory which I hope is basically sound. The -2-moity of ascorbate's
lactone ring is where it is generally oxidized. An OH group usually
resides there but is prone to oxidation in hi O2 environments such as
air. Several molecular groups can replace it an protect vit C ex vivo.
The most popular is phosphate, and only the Japanese seem to call it
ascorbate-2-O-phosphate. 2-asc phosphate might be the favorite
American name, I forget. It's also called long lasting vitamin C and
vitamin C prodrug. It's used in skin creams and animal feeds because
it lasts longer in air, and several studies have found it to have the
effects as vit C mole for mole. For the same reason it's used for in
vitro research, and some papers say it works where ascorbate doesn't.
This is just due to oxidation in the matrix because of contact with
air. I think Sigma in St. Louis sells it.
When ingested the phospate ion is stripped by gut cells and normal
vitamin C is what enters the body. When injected the phosphate ion is
stripped on entering the cells, so there is thought to be no benefit
for its use in vivo over vitamin C. Additionly it may be lacking in
vitamin C's protective effect in the plasma. (if injected) My take is
that any thing it can do in vitro, vitamin C MIGHT do in vivo, but
there are so many false leads from in vitro and animal studies
everything is speculative until proven in humans.
Presumably very hi doses will be needed since that is what's used in
vitro, and there is no evidence that associates normal doses with long
telomeres. One might check the Werner's forums in a year or so to see
if any have tried very hi dose vitamin C, or one might check their own
telomere length before and after a regimen of one gram/hr for six
months or so.
Thomas
jc101
A rudimentary knowledge of chemistry would have led one immediately to
look for salts; the magnesium ascorbyl phosphate and sodium ascorbyl
phosphates are readily available to industry. You are correct that the
phosphatases convert these to Asc in the body right away, this is very
basic biochemistry knowledge, so they are just a higher priced version
of ascorbic acid. Good for skin creams because they don't break down
in aqueous solution as does ascorbic acid.
Also, a ProC that survives in solution, also used for skin creams in
combination with MgAscPhosphate is L-ascorbyl 2-O-glucopyranoside -
since there is less glucosidase than phosphatase in human serum so it
releases Asc slower than does MAP, so there is a longer period of
action in the skin.
http://www.cossearch.ch/doc/apms/APMS_Physiol_0509EN.pdf
But this is a bunch of glucosidase in the gut so this turns into just
another toxic oxidizing dose of ascorbate as well upon digestion of
oral dose.
The ProC I use is 2-O-(β-D-glucopyranosyl)ascorbic acid. It is found
in Lycium barbarum also called wolfberry or goji berry. This ProC may
be available as a pure chemical one day. It's breakdown is slower and
some does enter the cells intact for slow release of C, the data on
just how much does is not available.
http://www.patentstorm.us/patents/7566698/description.html
http://en.wikipedia.org/wiki/Wolfberry
Search goji berry or wolfberry on ebay, or look in the Chinese
groceries for " Fructus lycii ". Looks like a cranberry colored
raisin. Eat an oz or two. If you soak them, they swell up like little
prunes. They taste ok, kind of sour-sweet, not too expensive.
Eat them separate from meals, as one should always separate fruits and
fruit juices from meals, as ascorbate greatly increases non-heme iron
absorption from meals - there will be some ascorbate in goji as well
as the proC. Iron is the chief main oxidizing toxin in our bodies. I
have now removed 20 units of blood by donation in the last 3.5 years,
lot of iron stored in older individuals and phlebotomy is the only way
to remove it.
Tetra-isopalmitoyl ascorbic acid (VC-IP) is lipophilic http://tinyurl.com/yavr948
and under development.
JLC