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PERIODICAL
FASTING AND CALORIC RESTRICTION FOR LIFE EXTENSION,
DISEASE TREATMENT AND CREATIVITY.
(clinical and experimental data)
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FASTING AND CALORIC RESTRICTION PRODUCE VARIOUS BIOLOGICAL
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2005
Department of Biostatistics,
University of Alabama, Ryals Public Health Building,
Room 327, 1665 University Boulevard, Birmingham, Alabama
35294-0022.
OBJECTIVE: We used a rodent
model of dietary obesity to evaluate effects of caloric
restriction-induced weight loss on mortality rate.
Research Measures and Procedures: In a randomized
parallel-groups design, 312 outbred Sprague-Dawley
rats (one-half males) were assigned at age 10 weeks
to one of three diets: low fat (LF; 18.7% calories
as fat) with caloric intake adjusted to maintain body
weight 10% below that for ad libitum (AL)-fed rat
food, high fat (HF; 45% calories as fat) fed at the
same level, or HF fed AL. At age 46 weeks, the lightest
one-third of the AL group was discarded to ensure
a more obese group; the remaining animals were randomly
assigned to one of three diets: HF-AL, HF with energy
restricted to produce body weights of animals restricted
on the HF diet throughout life, or LF with energy
restricted to produce the body weights of animals
restricted on the LF diet throughout life. Life span,
body weight, and leptin levels were measured. RESULTS:
Animals restricted throughout life lived the longest
(p < 0.001). Life span was not different among
animals that had been obese and then lost weight and
animals that had been nonobese throughout life (p
= 0.18). Animals that were obese and lost weight lived
substantially longer than animals that remained obese
throughout life (p = 0.002). Diet composition had
no effect on life span (p = 0.52). DISCUSSION: Weight
loss after the onset of obesity during adulthood leads
to a substantial increase in longevity in rats.
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Department of Hygiene, Kansai Medical
University.
Dietary restriction is known to
prolong life in laboratory animals. However, little
is known about the effects of dietary restriction on
physical performance. To evaluate physical performance,
we measured four item indices: time to climb out of
obstacles, time to escape restraint by gummed tape,
time hanging from a bar, and ability to resist slipping
every week. The diets of ICR mice were restricted from
the age of 7 weeks through 24 weeks. Body weight of
the diet-restricted mice decreased during the 7th to
9th weeks of age. After the 10th week, weight gain resumed.
In response to assigned tasks, the diet-restricted mice
performed better in all activities: they climbed out
of obstacles faster, freed themselves sooner from restraint
by gummed tape, hung from a bar longer, and better resisted
slipping down a slope. These results suggest that diet-restricted
mice have superior physical abilities, such as those
required to overcome or avoid risks to life, than do
ad-libitum-fed mice.
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Department of Internal Medicine
and Clinical Science, Catholic University, Rome, Italy.
PURPOSE OF REVIEW: This article
provides an overview of the most recent molecular and
clinical outcomes of studies that investigate the effect
of weight loss and calorie restriction on carbohydrate
metabolism, obtained either by dieting or bariatric
surgery. It will focus on aspects of carbohydrate metabolism
related to insulin action. The discussion begins by
describing attempts to restrain calories by shifting
the macronutrient balance from carbohydrates to a higher
protein and fat content. The topics covered include
insulin secretion and resistance, glucose homeostasis
and allostasis, changes in the secretive patterns of
adipose tissue and the entero-insular axis. RECENT FINDINGS:
Any improvement in glucose homeostasis, insulin sensitivity
and secretion after a low-carbohydrate high-fat diet
is still unproved. However, the restriction of dietary
carbohydrate seems to reduce glycogenolysis and endogenous
glucose production in type 2 diabetes mellitus, thus
inducing the amelioration of plasma glucose levels,
ultimately resulting in a reduction in the glycated
haemoglobin concentration. The increased endogenous
glucose production caused by enhanced gluconeogenesis
and glycogenolysis, reduced insulin sensitivity, mainly
caused by acquired defects of glucose transport and
phosphorylation, and the impairment of insulin secretion
all together contribute to maintain a chronic status
of hyperglycaemia. Weight loss and calorie restriction
restore glucose homeostasis and produce changes in the
secretive activities of adipose tissue and the entero-insular
axis. SUMMARY: Weight loss and calorie restriction partly
explain the positive changes of glucose disposal. The
multistep interaction of several factors at sites of
insulin action, insulin secretion, adipose tissue and
the entero-insular axis needs further investigation.
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2002
Laboratory of Neurosciences,
National Institute on Aging Gerontology Research Center
Baltimore, Maryland 21224, USA.
The adult brain contains small
populations of neural precursor cells (NPC) that can
give rise to new neurons and glia, and may play important
roles in learning and memory, and recovery from injury.
Growth factors can influence the proliferation, differentiation
and survival of NPC, and may mediate responses of
NPC to injury and environmental stimuli such as enriched
environments and physical activity. We now report
that neurotrophin _expression and neurogenesis can
be modified by a change in diet. When adult mice are
maintained on a dietary restriction (DR) feeding regimen,
numbers of newly generated cells in the dentate gyrus
of the hippocampus are increased, apparently as the
result of increased cell survival. The new cells exhibit
phenotypes of neurons and astrocytes. Levels of _expression
of brain-derived neurotrophic factor (BDNF) and neurotrophin-3
(NT-3) are increased by DR, while levels of _expression
of high-affinity receptors for these neurotrophins
(trkB and trkC) are unchanged. In addition, DR increases
the ratio of full-length trkB to truncated trkB in
the hippocampus. The ability of a change in diet to
stimulate neurotrophin _expression and enhance neurogenesis
has important implications for dietary modification
of neuroplasticity and responses of the brain to injury
and disease.
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2001
Laboratory of Neurosciences,
Gerontology Research Center, National Institute on
Aging, National Institutes of Health, Baltimore, Maryland
21224, USA.
In a long-term longitudinal
study of aging in rhesus monkeys, a primary objective
has been to determine the effects of aging and caloric
restriction (CR) on behavioral and neural parameters.
Through the use of automated devices, locomotor activity
can be monitored in the home cages of the monkeys.
Studies completed thus far indicate a clear age-related
decline in activity consistent with such observations
in many other species, including humans. However,
no consistent effects of CR on activity have been
observed. Selected groups of monkeys have also been
involved in brain imaging studies, using magnetic
resonance imaging (MRI) and positron emission tomography
(PET). MRI studies completed thus far reveal a clear
age-related decline in the volumes of the basal ganglia,
the putamen, and the caudate nucleus, with no change
in total brain volume. PET analysis has revealed an
age-related decline in the binding potential of dopamine
D2 receptors in the same brain regions. These results
are consistent with findings in humans. Although additional
longitudinal analysis is needed to confirm the present
results, it would appear that locomotor activity,
volume of the basal ganglia, as well as dopamine D2
receptor binding potential provide reliable, noninvasive
biomarkers of aging in rhesus monkeys.
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2000
Faculty of Food Science and Biotechnology,
Pukyong National University; 599-1 Daeyeon-Dong, Nam-Gu,
Pusan 608-737, Korea.
This study was to evaluate
the effect of dietary restriction (DR) on lifespan
and oxidative stress of dementia mouse model SAMP8
with impaired learning and memory. SAMP8 female mice
were fed either ad libitum (AL) or fed 60% of food
intake of AL. Results showed that basal metabolic
rates (BMR) were significantly lower (15 to 22%) in
DR with increased median and maximum lifespans, suggesting
feed and gross efficiencies were significantly lower
in DR than in AL. Grading score of senescence resulted
in a marked improvement about 2-fold by DR compared
with AL. The amounts of lipofuscin at 12 months were
significantly lowered 16% in DR than that of AL. Median
and maximal lifespans significantly increased (28.5%
and 16.4%, respectively) by DR, and also lowered superoxide
radical about 15~45% in DR compared with AL at 4,
8 and 12 months of age. On the other hand, superoxide
dismutase (SOD) activities were higher (about 15~30%)
in DR than those in AL group of SAMP8 except for 4
months of age. Our results suggest that 40% calorie
restricted SAMP8 can effectively suppress dementia-related
abnormalities during aging.
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Laboratory of Neurosciences,
Gerontology Research Center, National Institute on
Aging, Baltimore, MD 21224, USA.
The adult brain contains neural
stem cells that are capable of proliferating, differentiating
into neurons or glia, and then either surviving or
dying. This process of neural-cell production (neurogenesis)
in the dentate gyrus of the hippocampus is responsive
to brain injury, and both mental and physical activity.
We now report that neurogenesis in the dentate gyrus
can also be modified by diet. Previous studies have
shown that dietary restriction (DR) can suppress age-related
deficits in learning and memory, and can increase
resistance of neurons to degeneration in experimental
models of neurodegenerative disorders. We found that
maintenance of adult rats on a DR regimen results
in a significant increase in the numbers of newly
produced neural cells in the dentate gyrus of the
hippocampus, as determined by stereologic analysis
of cells labeled with the DNA precursor analog bromodeoxyuridine.
The increase in neurogenesis in rats maintained on
DR appears to result from decreased death of newly
produced cells, rather than from increased cell proliferation.
We further show that the _expression of brain-derived
neurotrophic factor, a trophic factor recently associated
with neurogenesis, is increased in hippocampal cells
of rats maintained on DR. Our data are the first evidence
that diet can affect the process of neurogenesis,
as well as the first evidence that diet can affect
neurotrophic factor production. These findings provide
insight into the mechanisms whereby diet impacts on
brain plasticity, aging and neurodegenerative disorders.
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1995
Department of Surgery, SUNY,
School of Medicine, Stony Brook 11794-8191.
The endogenous opiate alkaloid
content in tissues from fed, 24 h and 48 h fasted
rats was determined. Plasma morphine and codeine concentrations
did not change in response to fasting. Morphine levels
in the spleen increased 3-fold after 24 h of fasting
and were lower than fed rats by 48 h of fasting; no
change was detected in spleen codeine levels. Brain
morphine levels were elevated 5-fold after 24 h of
fasting and were two-fold higher than those of fed
rats after 48 h of fasting. Brain codeine levels did
not change with fasting. These results indicate that
opiate alkaloids are endogenously produced in rodent
tissues, particularly in the spleen, liver, and adrenals.
The synthesis of morphine, in the spleen and brain,
is maximally stimulated after 24 h of fasting, without
alterations in tissue codeine synthesis. These suggest
differential regulation of the endogenous synthetic
pathways of morphine and codeine in response to the
stress of fasting.
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1991
Department of Neurosciences,
Roche Institute of Molecular Biology, Nutley, New
Jersey.
The alteration of endogenous
opiate alkaloids during fasting state was investigated
in rats. The concentrations of morphine and codeine
in the cortex, midbrain, pons plus medulla, cerebellum,
adrenal gland and pancreas were measured using radioimmunoassay
for the opiates following high pressure liquid chromatography.
The morphine and codeine contents of fasting rats
showed maximum elevated levels in cortex, pons plus
medulla and pancreas after 2 days of fasting, but
after 1 day in midbrain. The opiate content of the
cerebellum showed a tendency for a continuous increase
during the 4 days. Adrenal glands of fasting rats
had elevated levels at days 3 and 4, although there
were great fluctuations within the groups.
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1990
Department of Psychosomatic Medicine,
Faculty of Medicine, Kyushu University, Fukuoka, Japan.
To identify the effects of
acute starvation on endogenous opioids in man, plasma
beta-endorphin (beta-EP) was measured in 17 patients
before, during and after fasting (Komaki, G. et. al.
1990). Patients were assigned a posteriori into two
groups: group A, comprised of 11 patients able to
tolerate 5-7 days of fasting, and group B, comprised
of 6 patients able to tolerate 10 days of fasting.
Changes in plasma beta-EP, serum cortisol, circulating
nutritional markers, and their relative levels were
assessed on the 5th and 10th days of fasting, and
on the 5th and 10th days of the refeeding period.
Beta-EP had increased by the 5th day (group A: 4.74
+/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01;
group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p
less than 0.05, and remained at 5.05 +/- 0.65 pmol/l
on the 10th day (group B: 0.05 less than p less than
0.1) during fasting. Group B had lower levels of plasma
beta-EP on the 5th day of fasting than group A (p
less than 0.05). However, serum cortisol levels changed
similarly in both groups. Plasma beta-EP showed no
significant correlation with either the percentage
of body weight lost or the body mass index (kg/m2)
over this study period. These findings indicate that
plasma beta-EP is elevated in the early phase of fasting,
while not directly being associated with body weight
changes. Plasma beta-EP is lower and less activated
in subjects who are able to tolerate fasting for longer
periods.
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1989
School of Behavioural Sciences,
Macquarie University, Sydney, NSW, Australia.
Two groups of aged rats, a
dietary restricted group fed approximately 10 g per
day from 6 weeks of age and a group fed ad lib throughout
their life span, were compared with a young adult
group on an 8-arm radial maze and a flavor memory
task. The young adult displayed efficient performance
on the radial-arm maze within the 15 day test period.
In contrast, both aged groups exhibited significantly
poorer performance in the maze in comparison with
the young adult group neither aged group differed
from chance at the end of the 15 days. The flavor
memory task required the animals to consume a novel
flavor. Their loss of neophobia, as indexed by their
subsequent consumption, was then taken as an indication
of the extent to which they remembered the novel flavor
and its effects. The young adult group lost their
neophobia more rapidly than either of the aged groups,
which did not appear to differ from each other. Taken
together, this pattern of results indicates that dietary
restriction does not protect animals from the memory
loss observed in aged animals.
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1987
Female C3B10RF1 mice maintained
on either a control (approximately 95 kcal/week) or
restricted (approximately 55 kcal/week) diet since
weaning were tested in a behavioral battery at 11
to 15 or 31 to 35 months of age (middle-aged vs. aged).
Age-related declines observed among control groups
in tests of motor coordination (rotorod) and learning
(complex maze) were prevented by the restriction regime.
In addition, diet restriction increased locomotor
activity in a runwheel cage among mice of both ages
but did not affect exploratory activity in a novel
arena.
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