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PubMed2002

Long-term programming of blood pressure by maternal dietary iron restriction in the rat.

We have reported that blood pressure was elevated in 3-month-old rats whose mothers were Fe-restricted during pregnancy. These animals also had improved glucose tolerance and decreased serum triacylglycerol. The aim of the present study was to determine whether these effects of maternal nutritional restriction, present in these animals at 3 months of age, can be observed in the same animals in later life. Pulmonary and serum angiotensin converting enzyme (ACE) concentrations were also measured to investigate whether the renin-angiotensin system was involved in the elevation of blood pressure observed in the offspring of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe-restricted dams at 16 months of age. Heart and kidney weight were increased as a proportion of body weight in the offspring of Fe-restricted dams. The pulmonary ACE concentration was not significantly different between the groups. The serum ACE concentration was significantly elevated in the offspring of Fe-restricted dams at 3 but not 14 months of age. There was a strong correlation between serum ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were not different between the maternal diet groups. Serum triacylglycerol tended to be lower in the offspring of Fe-restricted dams. There were no differences in serum non-esterified fatty acids or serum cholesterol between the maternal diet groups. This study provides further evidence that maternal nutrition has effects on the offspring that persist throughout life. At 16 months of age, the elevation of blood pressure in Fe-restricted offspring does not appear to be mediated via changes in ACE levels. Both cardiac hypertrophy and decreased serum triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that these changes may be initiated in utero.

Aging↗

PubMed2002

Effects of low dietary protein and different allocations of food during rearing and restricted feeding after peak rate of lay on egg production, fertility and hatchability in female broiler breeders.

1. A 3x2x2 factorial experiment was conducted with boiler breeder females to determine the effects of body weight gain (three levels) and conventional or lower crude protein concentrations in the rations during rearing, and restricted or ad libitum feeding after the peak rate of lay on egg production, fertility, hatchability, mortality and food consumption. 2. Compared with ad libitum feeding, conventional food restriction resulted in a decrease in average daily food consumption of 0.6 during rearing, 0.2 during early lay and an increase of 0.4 after the peak rate of egg production. Mortality was decreased by more than half. 3. Restricted birds had higher total and settable egg production, fewer defective or damaged eggshells and higher fertility and hatchability than those fed ad libitum. The modified (more generous) rearing programme resulted in lower rates of egg production and higher rates of mortality compared with the conventional food restriction programme. 4. Low-protein rearing rations were associated with higher rates of food intake, higher mortalities and lower rates of egg production than the conventional protein rations. There were no differences in the fertility or hatchability of eggs between birds fed on the two concentrations of dietary crude protein. 5. Ad libitum feeding post-peak was associated with higher rates of mortality to 60 weeks of age. Post-peak feeding had little effect on the rate of lay or egg weight in conventionally restricted birds fed high protein rations or in birds fed ad libitum. Restricted feeding post-peak decreased the rate of lay and egg weight in birds on the modified restriction programme and in conventionally restricted birds fed on the low protein rations. There was no effect of post-peak feeding on fertility or hatchability of eggs. 6. The total numbers of saleable chicks per kg food consumed were 1.83, 1.72 and 0.52 for conventional, modified and ad libitum feeding during rearing; 1.56 and 1.15 for restricted and ad libitum feeding post-peak: there were no differences associated with protein concentrations of rations fed during rearing.

Animal Welfare↗

PubMed2002

Effects of restricted feeding on physiological stress parameters in growing broiler breeders.

1. In previous studies, a lack of agreement in measurements of plasma corticosterone concentrations and heterophil:lymphocyte (H/L) ratio as physiological indices of stress, caused by hunger and frustration in restricted-fed broiler breeders, was observed. It could be suggested that the differences between previous studies were caused by differences in duration of restriction and time of the day of the measurements. Therefore, in the present study the plasma corticosterone concentration and the H/L ratio were again determined in restricted- and ad libitum-fed growing broiler breeders, taking possible causes of disagreement between previous studies into account. In addition, we measured the daily rhythm in body temperature and heart rate, and the corticosterone responses to an acute stressor as physiological indices of stress. 2. Female broiler breeders (64 per treatment, housed in groups of 4 birds) were used in the experiment. Behaviour, baseline plasma corticosterone concentrations and H/L ratio were determined at 21 d of age (immediately after the start of food restriction), and at 42 and 63 d of age. Body temperature, heart rate and activity were measured by radiotelemetry for 36 h at 49 and 70 d of age. In addition, the plasma corticosterone response to acute stress (5 min manual restraint) was measured at 77 or 78 d of age. 3. Restricted broiler breeders had higher plasma corticosterone concentrations at 42 and 63 d of age, but no differences in H/L. ratio were found between restricted birds and unrestricted control birds. Restricted broiler breeders had a higher corticosterone response to 5 min manual restraint than unrestricted birds. Restricted birds displayed a clear day-night rhythm in body temperature, heart rate and activity whereas such a rhythm was blunted in ad libitum-fed birds. 4. It is discussed that some physiological differences (plasma corticosterone concentrations, body temperature and heart rate) between ad libitum-fed and restricted broiler breeders may have been caused by differences in metabolic rate as well as by differences in the level of stress. It is concluded that a combination of behavioural measurements and a wide range of physiological parameters should be used for the assessment of stress in growing broiler breeders.

Animal Feed↗

PubMed1991

Effect of method and phase of nutrient restriction during rearing on productive performance of light hybrid pullets and hens.

1. An experiment was conducted to study the effect of method (low-lysine or quantity of food) and phase (starter or grower) of restriction during rearing on growth and laying performance in Leghorn hybrids. 2. A reduction in body weight gain was achieved by feeding pullets a low-lysine diet in either the starter phase (0-6 weeks of age: 4.0 g/kg digestible lysine) or the grower phase (7-18 weeks of age: 3.0 g/kg digestible lysine). 3. In each phase, the lysine restriction was compared with a daily food restriction, in which pullets received a quantity of food sufficient to pair-gain with their lysine-restricted counterparts. 4. The delay in onset of production was greatest in the lysine-restricted birds, for both phases of restriction. 5. Hens restricted during the grower phase laid heavier eggs than those restricted during the starter phase, despite having similar body weights at end of rearing. This effect was not influenced by the restriction method. 6. Production traits varied between pullets reared on different feeding strategies up to similar body weights at 18 weeks and onwards. It is concluded that body weight is not the only factor determining laying performance.

Animals↗

PubMed1998

Performance, incidence of metabolic disturbances and endocrine variables of food-restricted male broiler chickens.

1. This experiment was carried out to evaluate the productive and physiological consequences of a slight but long term food restriction of male broiler chickens from 2 commercial strains. 2. Cobb-500 and Ross chickens were submitted to a 20% food restriction from 8 to 21 d of age. Strain, food programme and their interactive effects were analysed in terms of consequences upon performance, mortality, incidence of sudden death syndrome (SDS) and ascites syndrome (AS), index of right cardiac hypertrophy and plasma concentrations of hormones related to metabolism and growth (T3, T4, T3:T4 ratio, IGF-I and GH). 3. Although some catch-up growth was observed by refeeding previously restricted birds after 22 d of rearing, food restriction decreased (P < or = 0.05) body weight at market age (42 d) irrespective of the strain, but improved (P < or = 0.05) food conversion. 4. The incidence of mortality was not high in non-restricted birds but SDS and AS caused more than 50% of deaths. Hypertrophic cardiac index was observed in chickens of both strains after 4 weeks of age and was higher in ad libitum fed birds. 5. During the period of food restriction, plasma T3 and IGF-I concentrations decreased whereas plasma T4 and GH concentrations increased compared to those of the age-matched ad libitum fed counterparts. During the subsequent ad libitum feeding period, few differences in circulating hormone concentrations were observed, except for the higher mean GH litres in previously food-restricted chickens at 35 d of age. 6. These results indicate that even a non-severe food restriction negatively affects body weight of 42-d-old male broilers but these are benefits with improved food efficiency and diminished mortality from metabolic disturbances. The hormone results suggest that the degree of food restriction applied was not severe because there was a very fast adaptive response with small and transient alterations in T3, T4 and GH plasma concentrations during the period of compensatory growth.

Animal Nutritional Physiological Phenomena↗

PubMed1982

Effects of restricted feeding in the growing and laying periods on the performance of White Leghorn by Australorp crossbred and White Leghorn strain cross chickens.

1. The effects of restricted feeding in the rearing and laying periods on the performance of three White Leghorn cockerel by Australorp pullet crossbred strains and one White Leghorn strain cross were studied in two experiments. 2. After feeding ad libitum in the rearing period, mean body weights of the three crossbred strains at 20 weeks of age were 1.75, 1.66 and 1.55 kg and that of the White Leghorn strain cross was 1.40 kg. The differing restrictions during rearing reduced mean body weight at 20 weeks by 14 to 33% and increased the time to sexual maturity by 8 to 23 d. 3. All restriction regimes during rearing increased mean egg weight and tended to reduce mortality in the laying period. Optimum hen-day egg number over 64 weeks of lay was obtained following mild restriction (14% body weight reduction) of the two heavier strains or ad libitum feeding of the lighter strains. Over 48 or 64 weeks of lay, egg number per hen housed (at 18 to 20 weeks of age) was optimised after moderately restricting (14 to 21% body weight reduction) the crossbred strains or feeding the White Leghorn strain cross ad libitum. 4. Over 64 weeks of lay, mortality was reduced from 19.3% to 10.5% in the lightest crossbred strains, in which a high proportion of deaths were associated with Marek's disease and lymphoid leucosis, by restriction during rearing. 5. Restricting food intake by 7 or 8% throughout the laying period reduced hen-housed egg number and mean egg weight of all four strains. The reduction in hen-day egg number associated with food restriction during lay was less for the heavier strains that had also been restricted during rearing. 6. Metabolisable energy intakes required to support maximum production over 64 weeks of lay were 1.23 to 1.36 MJ/d.

Animals↗

PubMed2002

Aging increases Nepsilon-(carboxymethyl)lysine and caloric restriction decreases Nepsilon-(carboxyethyl)lysine and Nepsilon-(malondialdehyde)lysine in rat heart mitochondrial proteins.

The present investigation studies the effect of aging, short-term and long-term caloric restriction on four different markers of oxidative, glycoxidative or lipoxidative damage to heart mitochondrial proteins: protein carbonyls (measured by ELISA); Nepsilon-(carboxyethyl)lysine (CEL), Nepsilon-(carboxymethyl)lysine (CML), and Nepsilon-(malondialdehyde)lysine (MDA-lys) measured by gas chromatography/mass spectrometry. Aging increased the steady state level of CML in rat heart mitochondria without changing the levels of the other three markers of protein damage. Short-term caloric restriction (six weeks) did not change any of the parameters measured. However, long-term (one year) caloric restriction decreased CEL and MDA-lys in heart mitochondria and did not change protein carbonyls and CML levels. The decrease in MDA-lys was not due to changes in the sensitivity of mitochondrial lipids to peroxidation since the measurements of the fatty acid composition showed that the total number of fatty acid double bonds was not changed by caloric restriction. The decrease in CEL and MDA-lys in caloric restriction agrees with the previously and consistently described finding that caloric restriction agrees with the previously and consistently described finding that caloric restriction lowers the rate of generation of reactive oxygen species (ROS) in rodent heart mitochondria, although in the case of CEL a caloric restriction-induced lowering of glycaemia can also be involved. The CEL and MDA-lys results support the notion that caloric restriction decreases oxidative stress-derived damage to heart mitochondrial proteins.

Aging↗

PubMed1982

Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells.

The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The present results are also informative for understanding the cellular interactions that are required for the generation of antigen-specific CTL responses. The Ia-restricted T cells that are required for the generation of H-2K/D-restricted anti-TNP CTL were shown to be helper T (TH) cells since (a) like TH cells functioning in antibody responses, they were specific for Ia determinants expressed by accessory cells, and (b) their function could be replaced by either TNP-primed, irradiated TH cells or by nonspecific soluble helper factors. It was also shown that the T-T cell interaction between Ia-restricted TH cells and H-2K/D-restricted precursor CTL (pCTL) is not Ia restricted. Rather, the results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors.

Animals↗

PubMed1988

Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.

To approach the mechanism that determines Ir gene-controlled high or low responsiveness to whole proteins, such as sperm whale myoglobin (SWMb), we compared the repertoires of high and low responder haplotype-restricted T cells for different myoglobin epitopes by limiting dilution frequency analysis. Poisson analysis was performed using long-term limiting dilution cell lines of (B10.BR [low] X B10.D2[high])F1 T cells maintained on high or low responder APCs. The cell lines were tested with SWMb peptides and fragments for T cell repertoire fine specificities and Ia restrictions. The frequency of SWMb-specific F1 T cells responsive on B10.BR (H-2k) APCs was 2.5-3.6-fold lower than on B10.D2 (H-2d) APCs. Strikingly, all of the H-2k-restricted T cells used I-Ek as a restriction element, whereas both I-Ad- and I-Ed-restricted T cells were found among the H-2d-restricted lines. The I-Ad-restricted T cells were dominant, and the majority was specific for the synthetic peptide 102-118. T cells specific for peptide 132-146, dominant in association with I-Ed, were less frequent. However, no detectable H-2k-restricted T cells were specific for either of these peptides, but instead they were specific for fragment 1-55 or peptide 59-80. Fragment 1-55 also stimulated a similar number of H-2d-restricted T cells. Therefore, the low response of F1 T cells on H-2k-presenting cells may be due to the failure to see myoglobin plus I-Ak, in particular the immunodominant site around Glu 109, in contrast to the dominant response of high responder mice (both H-2d and H-2s) focused on the I-A molecule and the site around residue Glu 109. The I-E- low responder B10 strain also failed to respond to peptide 102-118, supporting the idea that the low responder status results from a limited repertoire lacking response to 102-118 plus I-A. In those strains that respond to the immunodominant site 102-118, the frequency of T cells in the repertoire specific for this site was always considerably greater than that for other sites. These results suggest that there is an important difference between immunodominant epitopes and minor epitopes and that Ir gene-controlled low responsiveness to a natural whole protein may be due primarily to the failure to respond to a single immunodominant site, even though a number of other epitopes can be recognized.

Animals↗

PubMed2004

High diagnostic value of a radioiodine uptake test with and without iodine restriction in Graves' disease and silent thyroiditis.

The necessity of iodine restriction before radioiodine uptake (RAIU) testing for differentiation of thyrotoxicosis is controversial. The present study was undertaken to investigate the effects of iodine restriction on the RAIU value, and the necessity of iodine restriction in differentiating between Graves' disease (GD) and silent thyroiditis (ST). We investigated 415 patients, 277 of whom were patients with GD who had undergone iodine restriction before RAIU [GD(+)], 66 were patients with GD who did not undergo iodine restriction [GD(-)], 61 were patients with ST who had undergone iodine restriction [ST(+)], and the remaining 11 were patients with ST who did not undergo iodine restriction [ST(-)]. The RAIU value of the GD(+) group, 47.6% +/-14.4% (mean +/-standard deviation [SD]), was significantly higher than that of the GD(-) group, 42.4% +/- 17.6% (p = 0.03). However, the areas under the curves from the receiver operator characteristics analyses for the comparison between groups GD(+)/ST(+), GD(+)/ST(-), GD(-)/ST(+) and GD(-)/ST(-) were 0.99967, 0.99967, 0.98436, and 0.98485, and very high, respectively. High diagnostic value of the RAIU test was confirmed, but not affected by the presence of iodine restriction in the differentiation between GD and ST, therefore, iodine restriction before the RAIU test was unnecessary.

Adult↗

PubMed1995

Effect of energy compared with carbohydrate restriction on the lipolytic response to epinephrine.

Fasting enhances the lipolytic sensitivity of adipose tissue to beta-adrenergic stimulation. The importance of carbohydrate compared with total energy restriction in regulating the lipolytic response to epinephrine was evaluated. Five normal volunteers participated in two study protocols in a randomized cross-over design separated by a 3-wk period. In one study (total energy restriction) the subjects fasted for 84 h, whereas in the other (carbohydrate restriction) a lipid emulsion was infused for 12-15 h each day to meet resting energy requirements during an 84-h oral fast. Glycerol flux, an index of whole-body lipolysis, was measured by infusing [2H5]glycerol. Each subject was studied in the basal state and during a 1-h infusion of epinephrine (0.015 microgram kg(-1 min(-1) after 84 h of total energy restriction and after 84 h of carbohydrate restriction (12 h after the final lipid infusion). The lipolytic response to epinephrine, defined as the total area between the glycerol flux curve and baseline during 1 h of epinephrine infusion, was similar after total energy restriction (241 +/- 141 mumol/kg) and carbohydrate restriction (294 +/- 58 mumol/kg). We conclude that carbohydrate restriction, not total energy restriction, is responsible for the increase in lipolytic sensitivity observed during fasting.

Adipose Tissue↗

PubMed1996

Inhibition of tumor promotion and hepatocellular growth by dietary restriction in mice.

The effects of dietary restriction on the growth of hepatic focal lesions in phenobarbital (PB) promoted mice were examined. Dietary restriction which can inhibit many age-related diseases in rodents including hepatic cancer also decreases cell proliferation and increases apoptosis in the liver. In contrast, PB, a non-genotoxic rodent hepatocarcinogen, enhances the growth of hepatic focal lesions in mice and rats by increasing cell proliferation and inhibiting apoptosis. The present study examined the impact of dietary restriction on PB-induced hepatic tumor promotion. Focal lesions were produced by diethylnitrosamine (DEN) treatment (35 mg DEN/kg body weight injections, twice per week for 8 weeks). After lesions were produced, mice were placed into one of the following four groups: NIH-07 control diet/no PB (group 1); NIH-07 diet/500 mg PB per liter of drinking water (group 2); dietary restricted NIH-07 diet/no PB (group 3); and dietary restricted NIH-7 diet/ 500 mg PB per liter of drinking water (group 4). In this study, PB (500 mg/l) treatment to ad libitum-fed mice (group 2) enhanced focal lesion volume, number, and labeling index compared with group 1. In addition, PB treatment (group 2) inhibited apoptosis in normal and focal hepatocytes compared with untreated control mice (group 1). In contrast, in dietary restricted mice treated with PB (group 4) a significantly lower focal lesion volume, number and labeling index were seen compared with the ad libitum-fed/PB treatment group (group 2). PB treatment in dietary restricted mice (group 4) did not inhibit focal apoptosis, in fact, the incidence of focal apoptosis was increased in these mice compared with ad libitum and PB-treated mice (group 2). In dietary restricted mice treated with PB (group 4), the ability of PB to promote the growth of preneoplastic focal lesions was inhibited. These results show that dietary restriction can ablate the tumor promotional effects of PB in hepatic focal lesions and suggest that inhibition of focal lesion DNA synthesis and enhancement of apoptosis may be a mechanism for this effect.

Animals↗

PubMed2005

Fear of falling and related activity restriction among middle-aged African Americans.

BACKGROUND: The prevalence of fear of falling and related activity restriction, and their joint distribution with falls and falls efficacy, have been inadequately addressed in population-based studies of middle-aged and African-American groups. METHODS: The African American Health project is a population-based panel study of 998 African Americans born in 1936-1950 from two areas of metropolitan St. Louis (an impoverished inner-city area and a suburban area). Fear of falling, fear-related activity restriction, and 24 frailty-related covariates were assessed during in-home evaluations in 2000-2001. RESULTS: We found that 12.6% of participants reported having fear of falling without activity restriction, 13.2% had fear of falling with activity restriction, and 74.2% had no fear of falling. Neither fear of falling nor fear-related activity restriction varied significantly across three birth cohorts (1946-1950, 1941-1945, and 1936-1940). Lack of overlap of these two phenomena with having a fall in the past 2 years and low falls efficacy was considerable. When examined across three groups (no fear, fear without activity restriction, and fear with activity restriction), a consistent pattern of decreasing health status and social, emotional, and physical functioning was demonstrated. CONCLUSIONS: In this population-based sample of 49- to 65-year-old African Americans, fear of falling and fear-related activity restriction were surprisingly common and not well explained by prior falls or low falls efficacy. These phenomena were already evident by age 49-55. Further study is warranted, including detailed qualitative investigations examining the timing, precursors, and consequences of fear of falling and fear-related activity restriction in minority and majority populations.

Accidental Falls↗

PubMed2002

Comparison of the frequency of peptide-specific cytotoxic T lymphocytes restricted by self- and allo-MHC following in vitro T cell priming.

T cell recognition of antigenic peptides is thought to occur preferentially in the context of self-MHC. Here, we have tested the ability of four different K(b)-peptide combinations to stimulate self- and allo-restricted CTL responses in three different mouse stains. Responder T cells were primed in vitro with peptide-loaded stimulator cells, followed by limiting dilution assays to measure the number of peptide-specific cytotoxic T lymphocytes (CTL). For three peptides the number of CTL restricted by self-MHC was higher than for allo-MHC-restricted responses, although the difference was surprisingly small (3- to 5-fold). For the fourth peptide there was no detectable difference in the number of self- and allo-restricted CTL. Peptide titration experiments revealed that high avidity CTL were present in both the self- and allo-restricted setting. These data showed that the bias for preferred peptide recognition in the context of self-MHC imposed by positive thymic selection seems marginal. This raised the possibility that the TCR repertoire is inherently biased towards MHC restriction, independent of MHC-guided thymic selection. This was supported by the analysis of mature T cells generated from the thymus of MHC-deficient mice by lectin stimulation. K(b)-restricted CTL were found amongst these T cells at numbers similar to those of allo-restricted CTL. In summary, the data suggest that MHC-restricted peptide recognition is an inherent feature of the TCR repertoire and does not require thymic selection by MHC molecules.

Animals↗

PubMed1983

Temporal and compositional dietary restrictions modulate age-related changes in serum lipids.

Life-lon restriction of food, which markedly increases the length of life of rats, also delays the occurrence of age-related physiological deteriorations including the age-related changes in serum lipids. The aim of this study was to explore the effects of 1) food restriction limited to early life, 2) food restriction initiated in adult life and 3) restriction of protein without restriction of calories on the age-related changes in serum lipids. Food restriction started at 6 months of age was as effective as food restriction started at 6 weeks of age in modulating the age-related changes in serum lipids, whereas food restriction from 6 weeks to 6 months of age and restriction of protein but not calories were much less effective. Changes in the rate of very low density lipoprotein-triglyceride removal from the blood were not responsible for the age-related increase in triglyceride concentration or for the modulation of this increase by the dietary regimens. Age-related changes in serum or plasma levels of glucose, ketone bodies, insulin and glucagon were also measured and the modulating effects of the dietary regimens studied; possible relationships between the concentrations of these substances and the concentrations of the serum lipids are discussed.

Aging↗

PubMed1986

The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake.

We sought to clarify the impact of dietary restriction (undernutrition without malnutrition) on aging. Female mice from a long-lived strain were fed after weaning in one of six ways: group 1) a nonpurified diet ad libitum; 2) 85 kcal/wk of a purified diet (approximately 25% restriction); 3) 50 kcal/wk of a restricted purified diet enriched in protein, vitamin and mineral content to provide nearly equal intakes of these essentials as in group 2 (approximately 55% restriction); 4) as per group 3, but also restricted before weaning; 5) 50 kcal/wk of a vitamin- and mineral-enriched diet but with protein intake gradually reduced over the life span; 6) 40 kcal/wk of the diet fed to groups 3 and 4 (approximately 65% restriction). Mice from groups 3-6 exhibited mean and maximal life spans 35-65% greater than for group 1 and 20-40% greater than for group 2. Mice from group 6 lived longest of all. The longest lived 10% of mice from group 6 averaged 53.0 mo which, to our knowledge, exceeds reported values for any mice of any strain. Beneficial influences on tumor patterns and on declines with age in T-lymphocyte proliferation were most striking in group 6. Significant positive correlations between adult body weight and longevity occurred in groups 3-5 suggesting that increased metabolic efficiency may be related to longevity in restricted mice. Mice from groups 3-6 ate approximately 30% more calories per gram of mouse over the life span than did mice from group 2. These findings show the profound anti-aging effects of dietary restriction and provide new information for optimizing restriction regimes.

Aging↗

PubMed1993

Age-related changes in rat adipose tissue cellularity are altered by dietary restriction and exercise.

This study examined the effects of diet restriction and exercise training during aging on adipocyte size and number in male Wistar rats. An average of 30 weanling rats each were assigned to one of four experimental groups: ad libitum access to food, nonexercised; diet restricted, nonexercised; ad libitum access to food, exercised; diet restricted, exercised. Diet-restricted groups were allowed free access to food every other day, and, over the course of the study, they consumed 18-25% less than the groups allowed ad libitum access. Exercise training consisted of swimming on alternate days for up to 3 h per exercise period. Fat cell size, number and fat depot mass were determined in the inguinal, epididymal and perirenal fat depots at 12 mo of age and every 4 mo thereafter until 28 mo of age. Fat cell number was not influenced by age, exercise or food restriction in the epididymal or perirenal fat depots. Inguinal cell number was lower (P < 0.05) in the diet-restricted, exercised group at all ages compared with all other treatments. Dietary restriction and exercise training significantly decreased fat depot mass and fat cell size, with dietary restriction having the greatest effect. A bimodal distribution of adipocytes was observed in the epididymal, perirenal and inguinal depots of animals allowed ad libitum access to food. The presence of a large population of small fat cells (< 35 microns) indicated that even in the very aged animal there was the propensity for large variations in fat pad mass. The influence of diet restriction, exercise and aging on adipocyte cell size was highly variable and these effects were dependent on adipose tissue depot location.

Adipose Tissue↗

PubMed1993

Exercise intensity does not affect depression of resting metabolic rate during severe diet restriction in male Sprague-Dawley rats.

This study examined the effects of high and low intensity exercise on the resting metabolic rate during severe dietary restriction. We hypothesized that exercise would attenuate and/or offset the decline in resting metabolic rate during energy-deficit conditions. Thirty-two male 90-d-old Sprague-Dawley rats were divided into four groups: control, diet restriction only, diet restriction plus high intensity exercise, and diet restriction plus low intensity exercise. The body weights of the diet-restricted groups were rapidly reduced over 5 wk until rats in these three groups weighted 64% of control weight, and this difference in body weight was maintained for the last 5 wk of the study. The high and low intensity exercise groups ran 5 d/wk at 75 and 37.5%, respectively, of maximal running speed for 45 and 90 min/d, respectively. Resting metabolic rate (23-h oxygen uptake) was measured during wk 2, 4, 6, 8 and 10. Resting metabolic rate for the three diet-restricted groups was significantly lower (25-37%) than for the controls for all measurements. Exercise training had no effect on the diet-induced depression of resting metabolic rate, with the diet-restricted groups differing among each other by < 2% during the measurement periods. During severe diet-restriction, exercise-induced elevations of resting metabolic rate seem to be greatly reduced or eliminated. This absence of an exercise effect on resting metabolic rate persisted through 5 wk of reduced body weight maintenance. We conclude that during severe diet restriction, exercise offers no "protective" or enhancing effect on resting metabolic rate.

Animals↗