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PubMed1987

Calorie restriction modifies the delayed-type hypersensitivity response to the hapten trinitrobenzenesulfonic acid and to hapten-modified syngeneic spleen cells.

We have studied the influence of different degrees of calorie restriction on the induction and the regulation of the delayed type hypersensitivity (DTH) response to trinitrobenzenesulfonic acid (TNBS) and TNBS-modified spleen cells (TNBS-SC), injected by the sc or the iv route. Immediately after weaning, BALB/c mice were placed on restricted diets for either 2 or 4 weeks and then the DTH response was induced. The results showed that a 37.5% restriction in the food supply significantly depressed the level of the DTH response induced by the sc injection of TNBS-SC. In contrast, a 25% restriction in the food supply was insufficient to depress the response. Calorie restriction did not modify the inhibitory influence of an iv injection of TNBS-SC on the DTH response. However, iv presensitization with free hapten or the simultaneous injection of TNBS-SC by the iv and the sc routes did not significantly depress the DTH response in calorie-restricted mice, indicating a defect in the inhibitory regulation of the DTH response in these dietary groups.

Animals↗

PubMed1988

Study on the possible factors influencing the expression of H-2 restriction specificity and Ir phenotype of antigen-specific proliferative T cells with various types of radiation chimeras.

To better understand the factors described previously as influencing the manifestation of H-2 restriction specificity and Ir phenotype of T cells from radiation bone marrow chimeras, we also examined H-2 restriction specificity (Ir phenotype) of antigen (DNP-OVA, (T, G)-A-L, (H, G)-A-L)-specific proliferative T cells generated in various types of H-2 incompatible radiation chimeras prepared under our specific-pathogen-free (SPF) condition. The results indicated the following: (a) T cells generated in F1----parent bone marrow chimeras preferentially manifested host-type H-2 restriction specificity and Ir phenotype, regardless of the radiation dose (8.70 vs 11.59 Gy); (b) T cells recovered from twice-reconstituted F1----(PA----PB) chimeras manifested primary host (PB)-type Ir phenotype; (c) T cells which were recovered from (B10.Thy-1.1 X B10.BR.Thy-1.1)F1----parent (Thy-1.2) bone marrow chimeras and treated with anti-Thy-1.2 plus complement to deplete host-derived T cells still manifested preferentially the restriction specificity for host-type H-2; (d) PA-derived T cells which had differentiated in a fully allogeneic host (PB) environment of (PA + PB)----PB chimeras manifested fully allogeneic host-type Ir phenotype; (e) T cells from F1----parent chimeras that were prepared with 13-day fetal liver cells also manifested host H-2-restricted Ir phenotype; and (f) host preference for Ir phenotype of antigen-specific proliferative T cells was observed even in the case of F1----parent bone marrow chimeras reconstituted with "intact" bone marrow cells. The data suggest that thymic APCs, surviving host T cells or the source of stem cells (adult bone marrow vs 13-day fetal liver), do not necessarily play a significant role in the manifestation of H-2 restriction specificity and Ir phenotype of T cells generated in H-2 incompatible radiation chimeras.

Animals↗

PubMed1988

T suppressor efferent circuit which affects contact sensitivity to picryl chloride: the late-acting, second nonspecific T suppressor factor bears I-A determinants which are responsible for the I-A genetic restriction in its interaction with its target cell.

The T suppressor efferent circuit in the picryl (TNP) system, which inhibits the passive transfer of contact sensitivity, involves at least two antigen-nonspecific factors. The second nonspecific T suppressor factor (ns-2) bears I-A determinants of both the alpha and the beta chain as shown by affinity chromatography on immobilized anti-I-A monoclonal antibodies. Sequential absorption shows that the determinants of the alpha and beta chain occur on the same molecular complex. No absorption was obtained with anti-I-E antibody. There are two genetic restrictions associated with ns-2--the first is in its release from the second T suppressor efferent cell (on exposure to antigen) and the second is in its inhibitory interaction with its target cell. Both are MHC restricted and matching in I-A (but not I-E, or I-J) is sufficient. The question was asked whether the I-A of the ns-2 was directly responsible for the I-A genetic restriction in its action. F1 TsF was made in (H-2k X H-2b)F1 mice by injecting picrylated parental cells intravenously and triggering the release of ns-2 with the corresponding picrylated parental cells. Both I-Ak- and I-Ab-positive ns-2 were produced and were separated by affinity chromatography on immobilized anti-I-A monoclonal antibody. The I-A phenotype of these separated ns-2 of F1 origin determines the genetic restriction in their action; i.e., I-Ak+ ns-2 only inhibits passive transfer by H-2k cells and I-Ab+ ns-2 only acts on H-2b cells. In contrast, the I-A haplotype of the picrylated cell used to induce the Ts cell which makes ns-2 is unimportant. It was concluded that the I-A on the ns-2, and not a possible recognition site for I-A, serves as a restriction element. This finding suggests that ns-2 may act directly on the I-A-restricted T cell which mediates contact sensitivity.

Animals↗

PubMed1988

Mechanism of target cell lysis by cytotoxic T lymphocytes (CTL) employing RSV-induced H-2 congenic and recombinant mouse tumor cells: demonstration of soluble mediators released from H-2-restricted CTL clones.

The secretion and the specificity of cytotoxic mediators from H-2-restricted cytotoxic T lymphocytes (CTL) were examined using non-virus-producing target tumor cells induced by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) in B10 congenic and recombinant mice. By using rat concanavalin A supernatant, two H-2-restricted CTL clones were established from cytotoxic effector cells of B10.A(5R) mice primed with SR-RSV-induced syngeneic tumor Cell-free supernatants from the H-2-restricted CTL clones cocultured with syngeneic tumor cells had selectively high cytotoxic activity for syngeneic and H-2-compatible tumor cells, but not for H-2-incompatible tumor cells. YAC-1 cells, and B10.A(5R) blasts as defined in the 5-hr 51Cr-release assay. The cytotoxic activity was detected in the cell-free supernatants from the CTL clones cocultured with the CTL-sensitive syngeneic and H-2-compatible tumor cells, but not with the CTL-insensitive tumor cells and YAC-1 cells. The cytotoxic activity of the cell-free supernatant could be adsorbed by the syngeneic tumor cells, but not by YAC-1 and L(s) cells. Thus, the H-2-restricted CTL clones against SR-RSV-induced tumor cells were capable of releasing cytotoxic mediators by coculturing with syngeneic or H-2-compatible tumor cells, and the cytotoxic mediators showed a certain H-2-restricted manner in killing the target cells. These results suggest that the lysis of RSV-induced tumor cells by H-2-restricted CTL can at least in part be mediated by cytotoxic factors.

Adsorption↗

PubMed1989

CD4+ cytolytic T cell clones restricted to HLA class II, DR beta I, and DR beta III chains.

We have investigated the functional polymorphism of HLA class II antigens using CD4+ CTL clones. Seven CD4+ CTL clones were isolated from a healthy donor (HLA A2 A24; B8 B27; DRw17 DRw52a) by repeated stimulation with irradiated autologous EBV-transformed B cell lines (EBV-B). According to the HLA restriction specificity we divided CD4+ CTL clones into three subgroups: (i) DRw17-restricted CD4+ CTL clones; (ii) DRw52a-restricted CD4+ CTL clones; and (iii) the CD4+ CTL clones, of which the restriction specificity could not be assigned to products of a single HLA locus. Interestingly, DRw17-restricted CD4+ CTL clones distinguished between DRw17 and DRw18. Similarly, DRw52a-restricted CD4+ CTL clones distinguished between DRw52a, w52b, and w52c. There are four amino acids which differ between DRw17 and DRw18, whereas five differ between DRw52a and the other two alleles (DRw52b and DRw52c). The recent elucidation of the crystal structure of a human class I MHC molecule has identified the probable peptide binding site to be a cleft on the outer surface of the molecule, between two alpha-helices. On the basis of the theoretical model for HLA class II molecules, amino acid positions 26 and 28 (DRw17 vs DRw18) and amino acid positions 26, 28, and 74 (DRw52a vs the other two alleles) lie within the "cleft." We propose that amino acid positions 26 and 28 are very important sites with regard to the recognition of antigen-MHC complex by the TCR.

Binding, Competitive↗

PubMed1990

The effect of long-term caloric restriction on function of T-cell subsets in old mice.

The effect of caloric restriction (from weaning to old age) on CD3-stimulated CD4+ and CD8+ lymphocyte proliferation and calcium mobilization was examined. Young ad libitum (ad lib) fed, old ad lib fed, old calorically restricted, and old calorically restricted mice which were fed ad lib during the last 6 weeks of their life (restricted/refed) were compared in both BDF1 [(C57BL/6 x DBA/2)F1] and C57BL/6 mice. Proliferation of CD4+ cells was lower in old ad lib animals than in young animals; this difference was not seen in CD8+ cells. Those CD4+ cells which did proliferate in old ad lib animals underwent similar cell cycle progression as young cells. In calorically restricted and calorically restricted/refed animals, CD4+ cell proliferation was similar to the young animals, and CD8+ cells showed a higher proliferative capacity than cells from either young or old ad lib mice. Differences in proliferative capacity were not correlated with alterations in transmembrane signaling efficiency as peak [Ca2+]i was reduced in both T-cell subsets in all groups of old mice relative to young mice. Additionally, reduced [Ca2+]i was observed in the CD8+ subset for which there was no deficit in proliferation, and the enhanced proliferation seen in old restricted and old restricted/refed mice did not manifest as increased [Ca2+]i mobilization. The percentage of CD4+ cells from both mouse strains was reduced in all groups of old mice compared with young mice, while the percentage of CD8+ cells was generally similar in young and all groups of old mice. Our studies would suggest that lifelong caloric restriction of mice prevents the age-associated decrease in T-cell proliferative capacity but that the enhanced proliferation of these cells is not due to increased efficiency of transmembrane signaling.

Aging↗

PubMed1995

Lactational anovulation in non-human primates: restriction of nursing inhibits Prl secretion without precipitating the return of ovulatory menstrual cyclicity in cynomolgus monkeys.

To test the hypotheses that nighttime suckling and elevated nocturnal prolactin concentrations are essential for the continuation of lactational anovulation, the effects of restricting nursing to twelve h per day (either day or night) on maternal prolactin (Prl) levels and resumption of ovulatory menstrual cycles were studied in five groups of cynomolgus monkeys: Group 1: baby weaned: Group 2: baby fully nursed: Group 3: baby nursed night only; Group 4: baby nursed day only; and Group 5: baby housed with mother but not allowed to nurse. Restrictions were initiated at approximately 150 days postpartum and were achieved by placing a non-nursing jacket over the nursing jacket, which was worn 24 h/day. Fifteen out of seventeen monkeys remained anovulatory while housed with their infants, irrespective of the type of nursing restriction. First postpartum ovulations occurred approximately two months post-weaning. Plasma prolactin concentrations during both day and nighttime were significantly (p < 0.05) greater in the fully nursing group(s) than in all other groups. Fully nursing mothers had significantly (p < 0.01) greater prolactin concentrations at night than during the day. Among the restricted groups, the night only suckling group had significantly greater prolactin concentrations at night than the other restricted groups. There were no differences between daytime values, and within each restricted group there were no significant differences between day and night prolactin levels. We conclude that 1) nighttime suckling is not an absolute prerequisite for sustained lactational anovulation, and 2) suckling-induced hyperprolactinemia is not the principle mediator of lactational anovulation.

Animals↗

PubMed1985

Effects of cadmium ingestion and food restriction on energy metabolism and tissue metal concentrations in mallard ducks (Anas platyrhynchos).

The single and combined effects of cadmium ingestion and food restriction were examined in a 42-day experiment with male, juvenile mallard ducks. A 2 X 3 factorial design was employed consisting of two levels of food supply (ad libitum and 55% of ad libitum intake) and three levels of cadmium in the food (0, 5, or 50 micrograms Cd/g food). Cadmium ingestion alone had no effect on body or tissue weights, liver glycogen, plasma concentrations of glucose, urea, uric acid, nonesterified fatty acids (NEFA), triiodothyronine (T3), thyroxine (T4), or plasma or adrenal concentrations of corticosterone. The food restriction resulted in reduced body weights and reduced weights of livers, kidneys, and testes, increased adrenal weights, reduced liver glycogen, increased plasma NEFA concentrations, reduced plasma T3 and T4 concentrations, and increased adrenal corticosterone concentrations. In combination with the food restriction, cadmium ingestion further reduced plasma T3 concentrations and a similar trend was noted for T4. Additionally, the highest plasma NEFA concentrations and highest plasma and adrenal concentrations of corticosterone were observed in food-restricted ducks receiving the highest level of dietary cadmium. These results suggest the ability of cadmium ingestion to enhance food restriction-induced alterations in energy metabolism at levels of dietary cadmium that are by themselves without apparent effect. Also, cadmium ingestion resulted in increased kidney concentrations of copper and zinc; this effect on kidney zinc concentrations was increased in food-restricted ducks.

Administration, Oral↗

PubMed1983

In vitro contractile responses of the uterus from 'restricted diet' rats to adrenoceptor agonists. Influence of cyclo-oxygenase inhibitors.

The experiments concerned the effects of 15 days of restricted diet (50% of the normal food intake) on the magnitude of phasic contractions (Isometric Developed Tension, IDT) of uterine horns isolated from estrous rats. During 60 min following isolation, the IDT of normally fed controls diminished significantly whereas preparations from animals on the restricted diet had a better contractile constancy. This improved motility was prevented by blockers of prostaglandin (PG) synthesis as well as by return to a normal diet. Cumulative dose-response curves for isoproterenol, norepinephrine and methoxamine were made for the different groups. Isoproterenol and norepinephrine evoked a dose-dependent inhibition of IDT. This response was significantly shifted to the right with uteri from restricted diet animals. Following incubation with propranolol, norepinephrine stimulated the magnitude of contractions significantly more in uterine horns from restricted diet rats than in those from controls. The dose-response curve showing the enhancement of motility induced by methoxamine was displaced to the left in preparations from animals on a restricted diet. This shift was abolished by restoring the normal diet as well as by the presence in vitro of indomethacin or acetylsalicylic acid. The results suggest that tissue PGS, the prevalence of alpha-adrenoceptor mechanisms and the reduction of beta-ones, are involved in the contractile behavior of the uterus isolated from restricted diet rats.

Animal Feed↗

PubMed1992

Characterization of a sustained-release estrogen implant on oviduct development and plasma Ca concentrations in broiler breeder chicks: modulation by feed restriction and thyroid state.

The effect of estradiol-17 beta (E2) given as a sustained-release implant (Compudose 200) on concentrations of plasma calcium (Ca) and the development of the chick shell gland has been investigated in food-restricted and thyroid hormone-treated 6- to 8-week-old broiler breeder pullets. Chicks implanted with 0, 0.5, 1.0, 1.5, 2.0, and 3.0 Compudose pellets for 24 days (n = 6/group) revealed a dose-response relationship between plasma E2 and Ca and on oviduct growth. Plasma E2 concentrations were characterized by an initial burst phase for approximately 17 days, followed by a constant release phase. Histologic examination of shell gland tissue confirmed the dose related E2-induced development of microvilliated epithelium and tubular glands over time. Feed restriction initiated at 2 weeks of age markedly increased the response to the E2 implants. Birds (n = 8/group) implanted with 2 pellets and feed restricted had increased plasma concentrations of E2 and Ca, and increased growth of the oviduct (P less than 0.01) as compared to ad libitum implanted birds. In a separate study birds (n = 6/group) had restricted access to feed from 8 weeks of age and were implanted with 0, 2, 4, or 8 pellets. At intervals from 9 to 45 days after implantation one bird from each group was killed. Although concentrations of plasma Ca were significantly greater in feed-restricted birds (P less than 0.01), oviduct growth was only marginally increased by the food restriction program. Plasma Ca concentrations in broiler breeder pullets (n = 8/group) implanted with 1 or 3 pellets and injected with T3/T4 (100 micrograms/day) were significantly decreased (P less than 0.05). Injection of thyroid hormone also marginally decreased shell gland epithelial cell height (P less than 0.05) and development of microvilli (P less than 0.05). There was no effect of the administration of the goitrogen, propylthiouracil (10 micrograms/day im), on the E2 induced development of the shell gland.

Animals↗

PubMed1987

Effects of diet restriction on insulin-sensitive phosphodiesterase in rat fat cells.

Effects of insulin on insulin-sensitive phosphodiesterase were investigated using fat cells from diet-restricted rats. The enzyme activities in diet-restricted rats were higher in case of 0 to 30 nmol/L insulin concentrations than in ad lib fed rats. In fat cells from the diet-restricted rats, the curves shifted to the left and half-maximum stimulation was obtained at 0.04 nmol/L, compared to that of 0.18 nmol/L in ad lib fed rats. Specific binding of insulin for fat cells from diet restricted and ad lib fed rats was 6.0% and 5.4%/2 X 10(5) cells, respectively. However when insulin binding was expressed per unit cell surface area, it was significantly increased in fat cells from diet-restricted rats compared with that from control rats. These results suggest that the insulin effector system related to the phosphodiesterase activation is improved in fat cells from diet-restricted rats, in particular, sensitivity to insulin. These increases in sensitivity to the phosphodiesterase are possibly due to improvements of insulin receptor binding.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1987

The ventromedial hypothalamic nucleus is not essential for the prefeeding corticosterone peak in rats under restricted daily feeding.

The role of the ventromedial hypothalamic nucleus (VMH) in the generation of the prefeeding corticosterone peak was examined in rats under restricted daily feeding, under which daily meal supply was restricted to a fixed time in the early light period. Rats were lesioned in the VMH bilaterally and subjected to restricted daily feeding during two different post-operative phases and with two different durations of food presentation. A restricted feeding with free access to meal for 4 hr was imposed on the VMH-lesioned rats from 2 to 4 weeks after the lesion, when the daily food intake increased significantly (dynamic phase). The restricted feeding induced the prefeeding hormone peak in sham operated rats, but failed to develop it in the VMH-lesioned rats. On the other hand, the hormone peak appeared in the VMH-lesioned rats subjected to the feeding schedule from 8 to 10 weeks after the lesion, when the daily food intake was not different from the control (static phase). Moreover, the VMH-lesioned rats showed the hormone peak even in the dynamic phase when the access to meal was shortened to 1 hr. These results indicate that the VMH is not essential for the generation of the prefeeding corticosterone peak under restricted daily feeding, and suggest that a special metabolic state observed during the dynamic phase of VMH lesion prevents the development of the feeding-associated oscillation or its expression upon plasma corticosterone level.

Animals↗

PubMed1988

Restricted water intake influences male reproduction in two strains of house mice (Mus musculus).

Males from two strains of house mice (Mus musculus) were subjected to ten weeks of simulated drought in the laboratory. Water availability was reduced to 50% of ad lib intake for 5 weeks, then further restricted to 25% of ad lib consumption for an additional 5 weeks. Individuals of the highly inbred (CF1) strain were generally unaffected by water restriction. Testicular and epididymal mass of restricted CF1 animals did not change relative to control mice with ad lib access to water. Seminal vesicle mass decrease in water restricted CF1 males, but spermatogenesis was not significantly influenced. Body mass was reduced 25.4% after water restriction. In contrast, male F4 progeny of wild-caught Mus substantially reduced reproductive organ mass after limited water intake. Spermatogenesis was significantly diminished, but no animals became completely aspermatic. Body mass declined 12.6% in water restricted wild-strain Mus as compared to animals with ad lib water availability. These results are discussed in terms of their possible ecological significance.

Animals↗

PubMed1992

Effect of starvation or restriction on self-selection of macronutrients in rats.

Two models of food deprivation were used to study feeding behavior: starvation and dietary restriction. Rats starved for 3 days had decreased protein intake during the first 2 days of refeeding followed by increased carbohydrate consumption compared to controls. During refeeding, total intake was initially low compared to controls. In a second starvation study of similar design, brain tissues [raphe, ventromedial hypothalamus (VMH)] and sera were collected for analysis before refeeding and on day 2 of refeeding. Starved and starved-refed rats had increased serum beta-hydroxybutyrate versus controls. In rats restricted for 5 days (5 g/day), total food intake was increased immediately and was characterized primarily by carbohydrate intake. Serotonin levels in the raphe were decreased in restricted rats and 5-hydroxyindole acetic acid (5-HIAA) increased in restricted-refed rats. Restriction caused an increase in blood levels of beta-hydroxybutyrate and a decrease in insulin and glucose compared to controls. Fat selection remained low throughout all studies. The data suggest that starvation and food restriction elicit different patterns of macronutrient selection upon refeeding.

3-Hydroxybutyric Acid↗

PubMed1993

Effect of meal pattern during food restriction on body weight loss and recovery after refeeding.

The present study was designed to assess whether the pattern of meal feeding and the degree of caloric restriction have an effect on the body weights and refeeding patterns of restricted 4-month-old Long-Evans rats, relative to ad lib-fed controls. Four experimental groups of rats (n = 6 each) were put on different paradigms of food restriction, and a fifth group fed ad lib throughout served as controls. Twelve rats were restricted to receiving 50% of their mean baseline food intake, and 12 rats received only 70% of their baseline food intake. Each experimental group was further subdivided with one subgroup receiving all of their calories in one meal/day and the other with caloric intake equally divided into two meals/day. There was no statistical difference in the final body weights of the restricted groups. Although there appeared to be identical patterns of weight regain, none of the restricted groups ever reached the mean body weight of the controls because of an asymptotic leveling off of rate of body weight regain. Rats that had received 50% of baseline calories as two meals/day had significantly more adipose mass than did any other group. The present findings suggest that in the rat, refeeding and, hence, regulation, occurs to normalize rate of weight gain rather than absolute body weight.

Animals↗

PubMed1984

Liver lysosomal enzymes in rats during long-term dietary restriction. 1. Changes during the developmental period of life.

The specific activities of the lysosomal enzymes acid phosphatase, beta-galactosidase, arylsulphatase B and cathepsin D were determined in homogenates of livers of rats fed ad libitum and of rats subjected to long-term dietary restriction (10%, 30% and 50% of diet consumed by the ad libitum group). Dietary restriction began soon after weaning and animals were sacrificed 3, 9, 15 and 24 weeks later. Dietary restriction influenced all four enzymes but the changes depended on the enzyme as well as on the degree and duration of the dietary restriction. Total activity of acid phosphatase increased significantly at 3 weeks of restriction but only in the 50% group. The activity returned to normal values at 9 weeks. Arylsulphatase B increased in all experimental groups with a more pronounced change observed at 3 weeks and in the more severely restricted rats. No notable change in the activities of beta-galactosidase and cathepsin D activities was observed. Changes in the liver ultrastructure paralleled the biochemical changes seen at 3 weeks. Numerous autophagic vacuoles and dense bodies resembling age pigments were formed in the hepatocytic cytoplasm. Mitochondrial enlargement, increased matrical density and rough endoplasmic reticulum fragmentation were also noted. Few of these changes were observed at 9 weeks, and the hepatocyte's morphology was virtually normal at 15 and 24 weeks. The marked changes seen at 3 weeks may be a manifestation of the body's adaptive processes to the nutritional stress.

Acid Phosphatase↗

PubMed1989

Effect of long-term caloric restriction on brain monoamines in aging male and female Fischer 344 rats.

The present study examines the changes in central monoamines and their metabolites in aged male and female rats after long-term caloric restriction. Fischer 344 rats of both sexes (n = 5-10/group) were maintained on one of two dietary regimens: ad libitum NIH 31 diet or 60% by weight of the ad lib. intake (restricted), supplemented with vitamins and minerals. Animals received these diets from the age of 14 weeks until killed at 22.25 months of age. Caudate nucleus (CN), hypothalamus (HYPO), olfactory bulb (OB) and nucleus accumbens (NA) were assayed for content of norepinephrine (NE), dopamine (DA) and its metabolites (dihydroxyphenylacetic acid, DOPAC, and homovanillic acid, HVA) and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) using HPLC/EC. Relative to the ad lib. group, restricted rats of both sex showed significant decreases in NE content in CN, HYPO and OB. DA and 5-HT content were decreased significantly in the CN and HYPO. No significant changes were found in the levels of DA metabolites in all brain regions studied. While the 5-HIAA level was significantly reduced in the HYPO and NA of the female restricted rats, it was increased several-fold in the OB of the male restricted animals. These preliminary results suggest that long-term caloric restriction alters brain monoamine concentrations, an effect which may in turn modify the normal rate of aging.

Aging↗

PubMed1989

Effect of chronic food restriction in aging rats. I. Liver subcellular membranes.

To assess which membrane properties are modulated by the action of food restriction, characteristics of liver membrane structures of ad libitum-fed and food restricted Fischer 344 rats were analyzed over a wide age range. The results show that the yields of mitochondrial and microsomal membranes decreased in ad libitum-fed rats, but this age-related loss did not occur in food restricted rats until 30 months. Changes in membrane fatty acid composition which occurred with age were substantially modified by food restriction. Linoleic acid content progressively decreased in the membranes of ad libitum-fed rats with a concomitant increase of docosapentaenoic acid while an opposite pattern of change occurred in food restricted rats. Furthermore, food restriction maintained a low docosahexaenoic acid level in microsomes at all ages studied. While serum tocopherol increased markedly with age, there was little change in membrane tocopherol content in ad libitum-fed rats.

Age Factors↗