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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
EFFECTS |
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Department of Animal and Avian
Sciences, University of Maryland, 3115 Animal Sciences
Building, College Park, MD 20742, USA; Laboratory of
Experimental Gerontology, Gerontology Research Center,
National Institute on Aging, NIH, 5600 Nathan Shock
Drive, Baltimore, MD, USA.
The benefits of calorie restriction
(CR) have been established across a variety of vertebrate
and invertebrate species. Although the effects of
CR on lifespan in birds have not been examined, it
is clear that CR has beneficial effects on reproductive,
metabolic, and physiological function in adult poultry.
We examined the effects of CR in Japanese quail, a
rapidly maturing avian model, on reproductive endocrine
and neuroendocrine systems. Male Japanese quail were
pair fed at 0% ad libitum (AL), 20%, or 40% CR of
AL, recorded for juveniles (3-7 weeks of age) or adults
(12-16 weeks of age). Juvenile males on CR matured
more slowly, and both juvenile and adult males had
reduced plasma luteinizing hormone (LH) with CR. Adults
on 40% CR showed evidence of stress, with increased
plasma corticosterone and reduced testes weight and
circulating androgens. In a separate study, pituitary
gland response was tested in juvenile and adult castrated
males that had been on the same CR treatments. All
birds responded to gonadotropin releasing hormone
(GnRH) challenge, with LH release. However, the 40%
CR juvenile and adult birds had quantitatively lower
responses, suggesting central inhibition of the reproductive
axis. This hypothesis was tested by measurement of
sexual behavior and catecholamines known to stimulate
GnRH in hypothalamic regions that modulate these responses.
Results showed reduced norepinephrine in key hypothalamic
regions and reduced dopamine in posterior hypothalamus.
These data support the hypothesis that CR affects
reproductive function, with evidence for effects in
the central nervous system. These data are discussed
and compared to data collected in mammals, especially
the rhesus monkey, on the effects of timing and degree
of CR on reproductive and stress responses.
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Department of Physiology, University
of Kentucky College of Medicine, Lexington 40536-0084,
USA.
Restricting food intake to
60% that of ad libitum-fed rats results in an extended
life span, reduced incidence of age-related diseases,
and delayed reproductive senescence. We used this
animal model to further elucidate the mechanisms whereby
reproductive senescence is delayed. Female Sprague-Dawley
rats (7 wk old) were calorically restricted (CR; n
= 70) to 60% of the ad libitum(AL) intake measured
in control rats (n = 70). Rats were individually housed
under a 14L:10D cycle and fed daily within 1.5 h of
lights-off. Body weights were monitored every 2 wk,
and vaginal lavage was performed until rats were ovariectomized
(OVX). Two weeks after OVX, when rats were 4, 12,
or 18 mo of age, blood samples were taken via jugular
cannulae every 6 min for 3 h, and the plasma was assayed
for rat LH. The resulting profiles were examined through
use of Cluster analysis for mean LH concentrations,
LH pulse amplitude, and interval between LH pulses.
CR rats grew at a slower rate, and then maintained
body weights at approximately 76% that of AL controls
between 4 and 17.5 mo of age. The onset of persistent
estrus was delayed by 4 mo in CR rats. Average cycle
length was longer (p < 0.01) by less than 0.5 days
in CR compared with AL rats between 3.5 and 5.5 mo
of age but not different between 6.5 and 11.5 mo.
Mean levels of LH in OVX rats decreased with age (p
< 0.01), increased with caloric restriction (p
< 0.05), and decreased with declining cycling status
of the animal prior to OVX (regular [reg] vs. irregular
[ir] vs. persistent estrus [pe]; p < 0.05). The
increased mean LH due to caloric restriction was attributed
to an increase in mean pulse amplitude and not to
a decrease in time interval between LH pulses. From
these data we conclude that the beneficial effects
of caloric restriction on reproductive longevity may
be acting at the level of the hypothalamus and/or
pituitary to enhance LH secretion and do not require
a delay in puberty or a period of acyclicity.
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Institute of Human Ageing/Department
of Environmental and Evolutionary Biology, University
of Liverpool, Liverpool L69 3BX, UK.
Reproductive ageing in female
rodents is accompanied by changes in circulating peptide
and steroid hormones leading to irregular, lengthened
oestrous cycles prior to loss of fertility. In this
study, the effect of ageing is reported on steroid
hormone synthesis within individual ovarian follicles
and its retardation by restricted feeding for two
groups of ad libitum fed animals (114 and 350 days)
and two groups of diet-restricted animals (350 and
600 days). Follicles from ad libitum fed animals of
350 days showed a transition in follicular steroid
hormone synthesis to release elevated amounts of oestradiol-17beta
on all days of the cycle. This age-related change
in follicle steroid release was significantly delayed
by maintaining animals on a restricted feeding regime,
and was not complete even by 600 days of age. This
effect of diet as a means to manipulate ageing of
the follicular steroidogenic pathways provides a useful
system for investigating the control of reproductive
ageing in rodents.
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