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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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