Re: Resveratrol supplementation does not extend lifespan in ad libitum-fed rodents.
On Jul 4, 5:18 am, r...@my-deja.com wrote:It does seem likely to be
beneficial <<
These guys seem to agree.
---------------
Red Wine Ingredient Wards Off Effects Of Age On Heart, Bones, Eyes And
Muscle
Article Date: 06 Jul 2008 - 4:00 PDT
Large doses of a red wine ingredient can ward off many of the vagaries
of aging in mice who begin taking it at midlife, according to a new
report published online on July 3rd in Cell Metabolism, a Cell Press
publication. Those health improvements of the chemical known as
resveratrol - including cardiovascular benefits, greater motor
coordination, reduced cataracts and better bone density - come without
necessarily extending the animals' lifespan.
Sinclair and de Cabo's team further show evidence that resveratrol
mimics the beneficial effects of eating fewer calories. In mice, they
found that resveratrol induces gene activity patterns in multiple
tissues that parallel those induced by dietary restriction and every-
other-day feeding.
" From a health point of view, the quality of life of these mice at
the end of their days is much better," said Rafael de Cabo of the
National Institute on Aging. It suggests that resveratrol may "extend
productive independent life, rather than just extending life span."
" I was most surprised by how broad the effects were in the mice,"
added David Sinclair of Harvard Medical School. "Usually, you focus on
slowing down or ameliorating one disease at a time. In this case,
resveratrol influences a whole series of seemingly unrelated diseases
associated with aging." Sinclair said he expects some of the effect
seen in the mice would have even greater impact if they hold in
humans. That's because, unlike people, mice usually don't die as a
result of heart disease, or suffer from weakening bones.
Earlier studies showed that reducing calorie intake by 30%-50%, or
eating a nutritious diet every other day, can delay the onset of age-
related diseases, improve stress resistance, and decelerate functional
decline, the researchers said. Although dietary restriction has
beneficial effects in humans, such a diet is unlikely to be widely
adopted and would pose a significant risk to the frail, critically
ill, or the elderly.
Therefore, the researchers are on a quest for "dietary restriction
mimetic" compounds that provide some of the benefits without cutting
calories. One contender has been compounds like resversatrol that
activate SIRT1, a protein linked to long life in many species, from
yeast to mammals.
Indeed, studies have shown resveratrol can extend the lives of yeast,
worms, flies and fish. It also improves the health and survival of
obese mice fed a high-calorie diet. Now, de Cabo and Sinclair show
that those effects do indeed seem to take place by inducing the
physiology of dietary restriction. They placed one-year-old mice on a
standard control diet or every-other-day feeding with or without
resveratrol.
Resveratrol produced changes in the gene expression profiles of key
metabolic tissues, including liver and muscle, that closely resemble
those induced by dietary restriction, they report. Overall, the
animals' health improved under all dietary conditions, as reflected by
a reduction of osteoporosis, cataracts, vascular dysfunction, and
declines in motor coordination. However, the mice lived longer only
when they were fed a high-calorie diet, consistent with earlier
reports.
" In conclusion, long-term resveratrol treatment of mice can mimic
transcriptional changes induced by dietary restriction and allow them
to live healthier, more vigorous lives," they wrote. "In addition to
improving insulin sensitivity and increasing survival in [high-calorie
fed] mice, we show that resveratrol improves cardiovascular function,
bone density, and motor coordination, and delays cataracts, even in
nonobese rodents. Together, these findings confirm the feasibility of
finding an orally available dietary restriction mimetic."
Resveratrol treatment is already being tested in clinical trials for
type II diabetes, the researchers noted, and more potent molecules
with effects similar to resveratrol are also under development.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
The researchers include Kevin J. Pearson, National Institute on Aging,
National Institutes of Health, Baltimore, MD; Joseph A. Baur, Harvard
Medical School, Boston MA; Kaitlyn N. Lewis, National Institute on
Aging, National Institutes of Health, Baltimore, MD; Leonid Peshkin,
Harvard Medical School, Boston MA; Nathan L. Price, National Institute
on Aging, National Institutes of Health, Baltimore, MD, Harvard
Medical School, Boston MA; Nazar Labinskyy, New York Medical College,
Valhalla, NY; William R. Swindell, University of Michigan, Ann Arbor,
MI; Davida Kamara, National Institute on Aging, National Institutes of
Health, Baltimore, MD; Robin K. Minor, National Institute on Aging,
National Institutes of Health, Baltimore, MD; Evelyn Perez, National
Institute on Aging, National Institutes of Health, Baltimore, MD;
Hamish A. Jamieson, Centre for Education and Research on Ageing, and
the ANZAC Research Institute University of Sydney, Concord, Australia;
Yongqing Zhang, Gene Expression and Genomics Unit, National Institute
on Aging, National Institutes of Health, Baltimore, MD; Stephen R.
Dunn, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia,
PA ; Kumar Sharma, Translational Research in Kidney Disease, UCSD, La
Jolla, CA; Nancy Pleshko, Hospital for Special Surgery, New York, NY;
Laura A. Woollett, University of Cincinnati Medical Center,
Cincinnati, OH; Anna Csiszar, New York Medical College, Valhalla, NY ;
Yuji Ikeno, University of Texas Health Science Center at San Antonio,
and Research Service, Audie Murphy VA Hospital (STVHCS), San Antonio,
TX; David Le Couteur, Centre for Education and Research on Ageing, and
the ANZAC Research Institute University of Sydney, Concord, Australia;
Peter J. Elliott, Sirtris Pharmaceuticals Inc, Cambridge, MA; Kevin G.
Becker, Gene Expression and Genomics Unit, National Institute on
Aging, National Institutes of Health, Baltimore, MD; Placido Navas,
Centro Andaluz de Biologia del Desarrollo, and Centro de Investigacion
Biomedica en Red: Enfermedades Raras, Instituto de Salud Carlos III,
Sevilla, Spain; Donald K. Ingram, Nutritional Neuroscience and Aging
Laboratory, Pennington Biomedical Research Center, Louisiana State
University System, Baton Rouge, LA; Norman S. Wolf, University of
Washington, Seattle, WA; Zoltan Ungvari, New York Medical College,
Valhalla, NY ; David A. Sinclair, Harvard Medical School, Boston MA;
and Rafael de Cabo, National Institute on Aging, National Institutes
of Health, Baltimore, MD.
Source: Cathleen Genova
Cell Press
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
> On Jul 3, 9:24 pm, Taka <taka0...@gmail.com> wrote:
>
>
>
>
>
> > They say that high dose of RSV increase mortality due to heart
> > failure ... Well I think the RSV has to be titrated to the PUFAs and
> > particularly AA in the body. Profound benefits were found in mice who
> > were engorged with a very-high fat diet - 60% fat calorie - of course,
> > 60% Omega-6 will produce huge oxidative stress!
>
> > Taka
>
> > --------------------------------------
>
> > From Longevinex:
>
> > Follow-Up Resveratrol Mouse Study Confirms Red Wine Molecule Exerts
> > Profound Positive Effects Upon Health, But Also Produces A Surprise
> > Finding
>
> > In a follow-up study to the widely publicized 2006 mouse/resveratrol
> > study published in Nature Magazine (November 1, 2006), researchers now
> > provide more complete long-term analysis of the biological effects of
> > resveratrol as a molecular mimic of calorie restriction in animals.
>
> > The results, published in the journal Cell Metabolism, are jaw-
> > dropping, but they also come with a surprise. Resveratrol-fed elderly
> > mice show a marked reduction in signs of aging, including:
>
> > • Reduced albumin (a blood protein; elevated albumin often occurs with
> > heart failure)
> > • Decreased inflammation
> > • Superior blood-vessel health
> > • Increased elasticity of the aorta (the first blood vessel
> > outside the heart)
> > • Greater balance and coordination (motor function)
> > • Strikingly reduced cataract formation (even better than a
> > reduced-calorie diet)
> > • Preserved bone mineral density.
>
> > But surprisingly, while supplemental resveratrol did, as previously
> > reported, prolong the lifespan of mice who were engorged with a very-
> > high fat diet (60% fat calories, which no human could tolerate),
> > resveratrol did not prolong life in mice fed a standard calorie diet.
>
> > Two doses of resveratrol were employed in the mouse study, lower-dose
> > resveratrol (100 mg/kilogram of food (or ~364 milligrams for a 160-
> > pound/70 kilogram adult), or 400 mg/kilogram of food (~1565 milligrams
> > for the 160-pound/70 kilogram adult). While there were no long-term
> > detrimental effects noticed at modest doses, the lower-dose
> > resveratrol group appeared to consistently live a bit longer in all
> > groups than the higher-dose resveratrol groups (see chart). The
> > authors of the paper cite another animal study which showed that
> > 18,000 mg/kilogram of body weight (likely to be difficult for humans
> > to even intentionally achieve) did increase mortality due to heart
> > failure in a mouse study. So there may be decreasing health benefits
> > with increasing dosage.
>
> > The effects of a calorie-restricted diet on longevity are diminished
> > when the regimen is initiated at increasing ages. This drawback may
> > be overcome by resveratrol.
>
> > Of great interest is the effect resveratrol exerted over the Sirtuin1
> > gene, the gene that is activated when calorie restricted diets are
> > employed. However, “microarray data on the effects of SIRT1 over-
> > expression in these tissues are not available, making it currently
> > difficult to assess whether SIRT1 is a mediator of these effects,”
> > said researchers.
>
> > Matt Kaeberlein, a noted Sirtuin gene researcher at the University of
> > Washington in Seattle, offered his commentary, entitled “The Ongoing
> > Saga of Sirtuins and Aging,” in an accompanying article in Cell
> > Metabolism. Dr. Kaeberlein said:
>
> > Unfortunately, what has often been lost in reviews of the sirtuin
> > literature and reports in the popular media are the many complexities
> > and inconsistencies in our understanding of sirtuin biology as it
> > relates to aging. For example, in yeast, Sir2 over-expression
> > increases replicative life span (the span of time when a mother yeast
> > cell produces daughter cells, but shortens chronological life span,
> > which is a measure of the length of time a yeast cell can survive in a
> > non-dividing state.
>
> > Multiple labs have reported that sirtuins are not always
> > required for life-span extension from dietary restriction in either
> > yeast or worms. What makes the study by Li et al. particularly
> > interesting is the observation that Sirtuin1 gene inhibition causes
> > some phenotypes (groups with inherited genetic mutations) more
> > consistent with a slower rate of aging. For example, they show that
> > Siruin1 inhibition leads to increased IRS-2 acetylation, decreased
> > Insulin Growth Factor-1 signaling, and decreased Ras/ERK signaling.
> > Decreased Ras gene signaling increases life span in yeast, and reduced
> > insulin/Insulin Growth Factor-1-like signaling is associated with
> > increased life span in worms, flies, and mice. Supporting the idea
> > that inhibition of Sirtuin1 may slow aspects of aging in mice, studies
> > show enhanced resistance to oxidative stress in neuronal cells after
> > Sirtuin1 knockdown and reduced oxidation of proteins and lipids in
> > brains of Sirtuin1 knockout animals.
>
> > Taken together, these data may indicate that inhibition of
> > Sirtuin1 can be nerve-protective in aging animals and that some
> > features of aging are slowed rather than accelerated in animals whose
> > Sirtuin1 gene has been eliminated.
>
> > The one thing that seems clear is that sirtuin activators are
> > unlikely to be a ‘‘magic bullet’’ for aging. A more realistic hope is
> > that, as we continue to unravel the complexities of sirtuin biology,
> > targeted activation or inhibition of Sirtuin1—and perhaps other
> > sirtuins as well—will prove therapeutically useful toward a subset of
> > age-associated diseases. Such an achievement would be a huge step
> > forward in the transition of aging-related science from the laboratory
> > to the clinic, and we eagerly await the next chapter in the unfolding
> > saga that is sirtuin biology. --Matt Kaeberlein. (Cell Metabolism
> > July 2008)
>
> > The next chapter will be written by Longevinex®, which will unveil its
> > mouse study which measures the global-gene array effects of a calorie-
> > restricted diet, a resveratrol-fortified diet and a Longevinex®-
> > fortified diet. Of considerable interest, this upcoming study, to be
> > published in Experimental Gerontology, does not show that resveratrol
> > increases Sirtuin1 gene activity, as measured by messenger RNA. –
> > Copyright 2008 Resveratrol Partners LLC
>
> Although this summary says "resveratrol did not prolong life in mice
> fed a standard calorie diet. ", two points are worth noting. 1)
> resveratrol plus CR in the form of every-other-day (EOD) feeding DID
> extend lifespan by 15%, and 2) the strain of mice used in this study
> have previously been shown to not respond to either EOD or 40% caloric
> restriction.
>
> One cannot draw definite conclusions as to what exactly resveratrol
> will do in other species of mice, much less in human beings, from this
> study. It does seem likely to be beneficial.- Hide quoted text -
>
> - Show quoted text -
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