X-Message-Number: 27920
Date: Sun, 7 May 2006 19:59:35 -0700 (PDT)
From: Doug Skrecky <>
Subject: antiaging effects of blueberries

[Below are a variety of abstracts, and other supplemental information
regarding the benefits of regular blueberry consumption. An important
finding is that rodent chow supplemented with a mere 2% blueberry powder
rejuvenates aged rodent brain function to youthful levels. The human
equivalent dosage would be about 60 ml of blueberry juice, or two shot
glasses per day. Whether humans respond robustly to blueberrys, in a
manner similar to rodents, is not yet known.]

[Blueberry proanthocyanidins slow nematode aging via increases in osmotic
stress resistance. There is no mammalian longevity data yet.]

Aging Cell. 2006 Feb;5(1):59-68.
Blueberry polyphenols increase lifespan and thermotolerance in
Caenorhabditis elegans.
  The beneficial effects of polyphenol compounds in fruits and vegetables
are mainly extrapolated from in vitro studies or short-term dietary
supplementation studies. Due to cost and duration, relatively little is
known about whether dietary polyphenols are beneficial in whole animals,
particularly with respect to aging. To address this question, we examined
the effects of blueberry polyphenols on lifespan and aging of the
nematode, Caenorhabditis elegans, a useful organism for such a study. We
report that a complex mixture of blueberry polyphenols increased lifespan
and slowed aging-related declines in C. elegans. We also found that these
benefits did not just reflect antioxidant activity in these
compounds. For instance, blueberry treatment increased survival during
acute heat stress, but was not protective against acute oxidative
stress. The blueberry extract consists of three major fractions that all
contain antioxidant activity. However, only one fraction, enriched in
proanthocyanidin compounds, increased C. elegans lifespan and
thermotolerance. To further determine how polyphenols prolonged
C. elegans lifespan, we analyzed the genetic requirements for these
effects. Prolonged lifespan from this treatment required the presence of a
CaMKII pathway that mediates osmotic stress resistance, though not other
pathways that affect stress resistance and longevity. In conclusion,
polyphenolic compounds in blueberries had robust and reproducible
benefits during aging that were separable from antioxidant effects.

[Unfortunately, this is not an in-vivo test. If it were, it would suggest
a potent anti-aging effect in human stem cells.]

Stem Cells Dev. 2006 Feb;15(1):118-23.
Nutraceuticals synergistically promote proliferation of human stem cells.
  A viable alternative to stem cell transplantation is to design
approaches that stimulate endogenous stem cells to promote healing and
regenerative medicine. Many natural compounds have been shown to promote
healing; however, the effects of these compounds on stem cells have not
been investigated. We report here the effects of several natural compounds
on the proliferation of human bone marrow and human CD34(+) and
CD133(+) cells. A dose-related effect of blueberry, green tea, catechin,
carnosine, and vitamin D(3) was observed on proliferation with human bone
marrow as compared with human granulocyte-macrophage colony-stimulating
factor (hGM-CSF). We further show that combinations of nutrients produce
a synergistic effect to promote proliferation of human hematopoietic
progenitors. This demonstrates that nutrients can act to promote healing
via an interaction with stem cell populations.

[Control rats were 23 month old Long Evans rats which were restricted in
calories. The addition of a 2% blueberry diet rejuvenated their auditory
cortex functioning to youthful levels.]

Neurobiol Aging. 2005 Jun 9; [Epub ahead of print]
The effects of antioxidants in the senescent auditory cortex.
  We investigated whether a 2-month dietary supplementation of
antioxidants, in the form of blueberry phytochemicals, could reverse or
retard the age-related decline in temporal processing speed observed in
the aged rat. To this end, extracellular single unit responses to
frequency modulated (FM) sweeps were recorded in the primary auditory
cortex (AI) of aged rats that had been placed on either a
blueberry-supplemented or control diet 2 months prior to the
physiological recordings. Results showed that most cells recorded from
the blueberry-fed rats responded most vigorously to fast FM sweeps,
similar to that observed in young rats. In contrast, the majority of
cells recorded from the control rats showed a preference for slow FM
sweep rates. These results suggest that age-related changes in temporal
processing speed in A1 may be reversed by dietary supplementation of
blueberry phytochemicals.

[A variety of foods may be useful for reducing stroke related damage.]

Exp Neurol. 2005 May;193(1):75-84.
Dietary supplementation with blueberries, spinach, or spirulina reduces
ischemic brain damage.
  Free radicals are involved in neurodegenerative disorders, such as
ischemia and aging. We have previously demonstrated that treatment with
diets enriched with blueberry, spinach, or spirulina have been shown to
reduce neurodegenerative changes in aged animals. The purpose of this
study was to determine if these diets have neuroprotective effects in
focal ischemic brain. Adult male Sprague-Dawley rats were fed with equal
amounts of diets (blueberry, spinach, and spirulina) or with control
diet. After 4 weeks of feeding, all animals were anesthetized with
chloral hydrate. The right middle cerebral artery was ligated with a 10-O
suture for 60 min. The ligature was later removed to allow reperfusional
injury. Animals were sacrificed and brains were removed for caspase-3
enzymatic assays and triphenyltetrazolium chloride staining at 8 and 48 h
after the onset of reperfusion. A subgroup of animals was used for
locomotor behavior and biochemical assays. We found that animals which
received blueberry, spinach, or spirulina enriched diets had a
significant reduction in the volume of infarction in the cerebral cortex
and an increase in post-stroke locomotor activity. There was no
difference in blood biochemistry, blood CO2, and electrolyte levels among
all groups, suggesting that the protection was not indirectly mediated
through the changes in physiological functions. Animals treated with
blueberry, spinach, or spirulina had significantly lower caspase-3
activity in the ischemic hemisphere. In conclusion, our data suggest that
chronic treatment with blueberry, spinach, or spirulina reduces
ischemia/reperfusion-induced apoptosis and cerebral infarction.

Cell Transplant. 2005;14(4):213-23.
Blueberry extract enhances survival of intraocular hippocampal transplants.
  Transplantation of neural tissue has been explored as a potential
therapy to replace dead or dying cells in the brain, such as after brain
injury or neurodegenerative disease. However, survival of transplanted
tissue is poor, especially when the transplant recipient is of advanced
age. Recent studies have demonstrated improvement of neuronal deficits in
aged animals given a diet supplemented with blueberry extract. The
present study focuses on the survival of fetal hippocampal transplants to
young (4 months) or middle-aged (16 months) animals with or without
dietary supplementation with blueberry extract. Results indicate that
fetal hippocampus transplanted to middle-aged host animals exhibits poor
survival characterized by reduced growth and compromised tissue
organization. However, when middle-aged animals were maintained on a diet
supplemented with 2% blueberry extract, hippocampal graft growth was
significantly improved and cellular organization of grafts was comparable
to that seen in tissue grafted to young host animals. Thus, the data
suggest that factor(s) in blueberries may have significant effects on
development and organization of this important brain region.

[A 2% blueberry powder diet rejuvenated HSP70 response in 21 month old
Fischer 344 rats to youthful levels.]

Neurobiol Aging. 2006 Feb;27(2):344-50.
Blueberry supplemented diet reverses age-related decline in hippocampal
HSP70 neuroprotection.
  Dietary supplementation with antioxidant rich foods can decrease the
level of oxidative stress in brain regions and can ameliorate age-related
deficits in neuronal and behavioral functions. We examined whether
short-term supplementation with blueberries might enhance the brain's
ability to generate a heat shock protein 70 (HSP70) mediated
neuroprotective response to stress. Hippocampal (HC) regions from young
and old rats fed either a control or a supplemented diet for 10 weeks
were subjected to an in vitro inflammatory challenge (LPS) and then
examined for levels of HSP70 at various times post LPS (30, 90 and 240
min). While baseline levels of HSP70 did not differ among the various
groups compared to young control diet rats, increases in HSP70 protein
levels in response to an in vitro LPS challenge were significantly less
in old as compared to young control diet rats at the 30, 90 and 240 min
time points. However, it appeared that the blueberry diet completely
restored the HSP70 response to LPS in the old rats at the 90 and 240 min
times. This suggests that a short-term blueberry (BB) intervention may
result in improved HSP70-mediated protection against a number of
neurodegenerative processes in the brain. Results are discussed in terms
of the multiplicity of the effects of the BB supplementation which appear
to range from antioxidant/anti-inflammatory activity to signaling.

[An 8% blueberry powder diet was used here.]

J Nutr Biochem. 2006 Feb;17(2):109-16. Epub 2005 Jun 20.
Wild blueberry (Vaccinium angustifolium) consumption affects the
composition and structure of glycosaminoglycans in Sprague-Dawley rat aorta.
  It has been documented that increased intake of polyphenols may provide
protection against coronary heart disease and stroke. Blueberries
(Vaccinium angustifolium) are one of the richest sources of antioxidants
among fruits and vegetables. Phenolic compounds from berry extracts
inhibit human low density lipoprotein and liposome
oxidation. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are
structural components of aortas with great structural diversity. Their
interaction with compounds such as enzymes, cytokines, growth factors,
proteins and lipoproteins and their subsequent role in degenerative
diseases has been documented. We investigated the effects of a diet rich
in blueberries on the content and structure of GAGs. Sprague-Dawley rats
were fed either a control (C) or a blueberry (B) diet for 13
weeks. Aortic tissue GAGs were isolated with papain digestion, alkaline
borohydride treatment and anion-exchange chromatography. Cellulose
acetate electrophoresis and treatment of the fractions with specific
lyases revealed the presence of three GAG populations, i.e. hyaluronan
(HA), heparan sulfate (HS) and galactosaminoglycans
(GalAGs). Disaccharide composition was determined by high-performance
capillary electrophoresis following enzymatic degradation. A 13% higher
amount of total GAGs in aortas of B-fed rats was attributed to a higher
content of GalAGs (67%). Determination of the sulfated disaccharides
showed an overall lower concentration of oversulfated disaccharides in
both HS and GalAG populations in the aortas of the B group. Our results
demonstrate for the first time that a diet rich in blueberries results in
structural alterations in rat aortic tissue GAGs. These changes may
affect cellular signal transduction pathways and could have major
consequences for the biological function of GAG molecules within the
vascular environment.

J Dermatolog Treat. 2004 Jul;15(4):222-6.
Supplementation with Evelle improves skin smoothness and elasticity in a
double-blind, placebo-controlled study with 62 women.
  OBJECTIVE: To investigate whether nutritional intervention with a
proprietary formulation and other micronutrients may favourably alter
skin roughness and elasticity. METHODS: Sixty-two women aged 45-73 years
participated in a double-blind, placebo-controlled trial testing the
efficacy of a proprietary oral supplement for skin nutrition (Evelle), for
improvement of skin elasticity and roughness. The active ingredients were
vitamins C and E, carotenoids, selenium, zinc, amino acids and
glycosaminoglycans, blueberry extract and Pycnogenol. RESULTS: Skin
elasticity, measured using an optical cutometer, was found to be
statistically significantly increased by 9% after 6 weeks of treatment
compared with placebo (p=0.0351). Skin roughness, as evaluated by
three-dimensional microtopography imaging, was found to be statistically
significantly lowered by 6% compared with the control group after 12 weeks
treatment (p=0.0157). CONCLUSION: Evelle can potentially improve visible
signs of cutaneous ageing.

[2% blueberry powder diet again.]

Nutr Neurosci. 2004 Oct-Dec;7(5-6):309-16.
Modulation of hippocampal plasticity and cognitive behavior by short-term
blueberry supplementation in aged rats.
  During aging, reductions in hippocampal neurogenesis are associated
with memory decline indicating a causal relationship. Indeed,
insulin-like growth factor-1 (IGF-1), a major activator of the
extracellular receptor kinase pathway that is central in learning and
memory processes, is also a key modulator of hippocampal
neurogenesis. Previously, we showed that age-related declines in spatial
memory tasks can be improved by antioxidant-rich diets containing
blueberries. In this study, to begin to understand the mechanisms
responsible for the beneficial effects of blueberries, we assessed
changes in hippocampal plasticity parameters such as hippocampal
neurogenesis, extracellular receptor kinase activation, and IGF-1 and
IGF-1R levels in blueberry-supplemented aged animals. Our results show
that all these parameters of hippocampal neuronal plasticity are
increased in supplemented animals and aspects such as proliferation,
extracellular receptor kinase activation and IGF-1 and IGF-1R levels
correlate with improvements in spatial memory. Therefore, cognitive
improvements afforded by polyphenolic-rich fruits such as blueberries
appear, in part, to be mediated by their effects on hippocampal

[Blueberry had an edge here.]

J Alzheimers Dis. 2004 Aug;6(4):403-11; discussion 443-9.
Fruit extracts antagonize Abeta- or DA-induced deficits in Ca2+ flux in
M1-transfected COS-7 cells.
  Evidence suggests that there is a selective sensitivity to oxidative
stress (OSS) among muscarinic receptor (MAChR) subtypes with M1, M2 and
M4 showing > OSS than M3 or M5 subtypes in transfected COS-7 cells. This
may be important in determining the regional specificity in neuronal
aging and Alzheimer disease (AD). We assessed the effectiveness of
blueberry (BB) and other high antioxidant (HA) fruit extracts
(boysenberry, BY; cranberry, CB; black currant, BC; strawberry, SB; dried
plums, DP; and grape, GR) on the toxic effects of Abeta 25-35 (100
microM, 24 hrs) and DA (1 mM, 4 hrs) on calcium buffering
(Recovery) following oxotremorine (750 microM) -induced depolarization in
M1AChR-transfected COS-7 cells, and on cell viability following DA (4
hrs) exposure. The extracts showed differential levels of Recovery
protection in comparisons to the non-supplemented controls that was
dependent upon whether DA or Abeta was used as the
pretreatment. Interestingly, assessments of DA-induced decrements in
viability revealed that all of the extracts had some protective
effects. These findings suggest that the putative toxic effects of Abeta
or DA might be reduced by HA fruit extracts.

Nutr Neurosci. 2004 Apr;7(2):75-83.
Blueberry supplemented diet: effects on object recognition memory and
nuclear factor-kappa B levels in aged rats.
  It has been reported that an antioxidant-rich, blueberry-supplemented
rat diet may retard brain aging in the rat. The present study determined
whether such supplementation could prevent impaired object recognition
memory and elevated levels of the oxidative stress-responsive protein,
nuclear factor-kappa B (NF-kappaB) in aged Fischer-344 rats. Twelve aged
rats had been fed a 2% blueberry supplemented diet for 4 months prior to
testing. Eleven aged rats and twelve young rats had been fed a control
diet. The rats were tested for object recognition memory on the visual
paired comparison task. With a 1-h delay between training and testing,
aged control diet rats performed no better than chance. Young rats and
aged blueberry diet rats performed similarly and significantly better
than the aged control diet group. Levels of NF-kappaB in five brain
regions of the above subjects were determined by western blotting
assays. In four regions, aged control diet rats had significantly higher
average NF-kappaB levels than young animals on the control diet. In four
regions, aged blueberry diet rats had significantly lower levels of
NF-kappaB than aged control diet rats. Normalized NF-kappaB levels
(averaged across regions and in several individual regions) correlated
negatively and significantly with the object memory scores.

[0.0230% blueberry extracts were used here.]

Bull Exp Biol Med. 2004 Mar;137(3):249-51.
Comparison of antioxidants in the ability to prevent cataract in
prematurely aging OXYS rats.
  The biological model of prematurely aging OXYS rats is proposed for
evaluation of anticataract activity of preparations. Pathological changes
in the lens develop in 2-month-old OXYS rats. By the 6th month of life
cataract morbidity rate attains 100%. Adrusen Zinco, Mirtilene Forte,
blueberry extract, and vitamin E (Russian and from Sigma) possessing
antioxidant properties and given with food decreased the number of OXYS
rats with cataract. The preparation from blueberry Mirtilene Forte and
blueberry extract normalized the content of lipid peroxidation products
in the blood. Blueberry extract manufactured in Russia decreased the index
of lipid atherogenicity that was high in OXYS rats.

[2% blueberry powder diet completely blocked the development of Alzheimer
disease in transgenic mice.]

Nutr Neurosci. 2003 Jun;6(3):153-62.
Blueberry supplementation enhances signaling and prevents behavioral
deficits in an Alzheimer disease model.
  Previously, we showed that blueberry (BB) supplementation reversed the
deleterious effects of aging on motor behavior and neuronal signaling in
senescent rodents. We now report that BB-fed (from 4 months of age) APP +
PS1 transgenic mice showed no deficits in Y-maze performance (at 12
months of age) with no alterations in amyloid beta burden. It appeared
that the protective mechanisms are derived from BB-induced enhancement of
memory-associated neuronal signaling (e.g. extracellular signal-regulated
kinase) and alterations in neutral sphingomyelin-specific phospholipase C
activity. Thus, our data indicate for the first time that it may be
possible to overcome genetic predispositions to Alzheimer disease through

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