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Sample records for lifelong calorie restriction

  1. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise

    PubMed Central

    Wohlgemuth, Stephanie Eva; Seo, Arnold Young; Marzetti, Emanuele; Lees, Hazel Anne; Leeuwenburgh, Christiaan

    2009-01-01

    Sarcopenia, loss of muscle mass and function, is a common feature of aging. Oxidative damage and apoptosis are likely underlying factors. Autophagy, a process for the degradation of cellular constituents, may be a mechanism to combat cell damage and death. We investigated the effect of age on autophagy and apoptosis in plantaris muscle of male Fischer344 rats that were either fed ad libitum, or mild, life-long calorie restricted (CR) alone or combined with life-long voluntary exercise. Upstream autophagy regulatory proteins were either upregulated with age (Beclin-1) or unchanged (Atg7 and 9). LC3 gene and protein expression pattern as well as LAMP-2 gene expression, both downstream regulators of autophagy, however, suggested an age-related decline in autophagic degradation. Atg protein expression and LC3 and LAMP-2 gene expression were improved in CR rats with or without exercise. The age-related increase in oxidative damage and apoptosis were attenuated by the treatments. Both, oxidative damage and apoptosis correlated negatively with autophagy. We conclude that mild CR attenuates the age-related impairment of autophagy in rodent skeletal muscle, which might be one of the mechanisms by which CR attenuates age-related cellular damage and cell death in skeletal muscle in vivo. PMID:19903516

  2. Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction.

    PubMed

    Hofer, Tim; Servais, Stephane; Seo, Arnold Young; Marzetti, Emanuele; Hiona, Asimina; Upadhyay, Shashank Jagdish; Wohlgemuth, Stephanie Eva; Leeuwenburgh, Christiaan

    2009-05-01

    Loss of cardiac mitochondrial function with age may cause increased cardiomyocyte death through mitochondria-mediated release of apoptogenic factors. We investigated ventricular subsarcolemmal (SSM) and interfibrillar (IFM) mitochondrial bioenergetics and susceptibility towards Ca(2+)-induced permeability transition pore (mPTP) opening with aging and lifelong calorie restriction (CR). Cardiac mitochondria were isolated from 8-, 18-, 29- and 37-month-old male Fischer 344 x Brown Norway rats fed either ad libitum (AL) or 40% calorie restricted diets. With age, H(2)O(2) generation did not increase and oxygen consumption did not significantly decrease in either SSM or IFM. Strikingly, IFM displayed an increased susceptibility towards mPTP opening during senescence. In contrast, Ca(2+) retention capacity of SSM was not affected by age, but SSM tolerated much less Ca(2+) than IFM. Only modest age-dependent increases in cytosolic caspase activities and cytochrome c levels were observed and were not affected by CR. Levels of putative mPTP-modulating components: cyclophilin-D, the adenine nucleotide translocase (ANT), and the voltage-dependent ion channel (VDAC) were not affected by aging or CR. In summary, the age-related reduction of Ca(2+) retention capacity in IFM may explain the increased susceptibility to stress-induced cell death in the aged myocardium.

  3. Calorie restriction and stroke

    PubMed Central

    2011-01-01

    Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke. PMID:21910904

  4. Life extension by calorie restriction in humans.

    PubMed

    Everitt, Arthur V; Le Couteur, David G

    2007-10-01

    Long-term reduction in energy intake in the diet (calorie restriction [CR]) extends the life of the laboratory rat by about 25%. However, in humans there are no life-long studies of CR, but only short-term trials which indicate that 20% CR acting over periods of 2-6 years is associated with reduced body weight, blood pressure, blood cholesterol, and blood glucose--risk factors for the major killer diseases of cardiovascular disease and diabetes. In addition, recent research has shown that CR for 6 months is able to improve biomarkers for longevity (deep body temperature and plasma insulin) and thus should increase life expectancy. The magnitude of the life-extension effect of CR in humans can only be estimated. The Okinawans, the longest-lived people on earth, consume 40% fewer calories than the Americans and live only 4 years longer. Similarly, women in United States consume 25% fewer calories than men and live 5 years longer. From the survival studies of overweight and obese people, it is estimated that long-term CR to prevent excessive weight gain could add only 3-13 years to life expectancy. Thus the effects of CR on human life extension are probably much smaller than those achieved by medical and public health interventions, which have extended life by about 30 years in developed countries in the 20th century, by greatly reducing deaths from infections, accidents, and cardiovascular disease.

  5. The Benefits of Calorie Restriction and Calorie Restriction Mimetics as Related to the Eye

    PubMed Central

    Anekonda, T.S.

    2010-01-01

    The effects of calorie restriction without malnutrition seem to possess many beneficial effects in numerous disease states. Recently, studies related to calorie restriction mimetics that biochemically mimic the effects of calorie restriction are also becoming increasingly popular. Both calorie restriction and calorie restriction mimetics trigger an adaptive response reminiscent of mild-stress or low-dose toxic response, which is frequently referred to as hormesis in the toxicology literature. Although some benefits of calorie restriction and calorie restriction mimetics have been studied, the role of hormesis-related pathways in the eye has not been given a special attention. This review will present the current literature on calorie restriction and calorie restriction mimetics as related to most prominent eye diseases and provide insights on the therapeutic role of hormesis in eye diseases. PMID:20844606

  6. Newer antidiabetic drugs and calorie restriction mimicry.

    PubMed

    Kalra, Sanjay; Jacob, Jubbin Jagan; Gupta, Yashdeep

    2016-01-01

    De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition) in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR) to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.

  7. Counting calories in Drosophila diet restriction.

    PubMed

    Min, Kyung-Jin; Flatt, Thomas; Kulaots, Indrek; Tatar, Marc

    2007-03-01

    The extension of life span by diet restriction in Drosophila has been argued to occur without limiting calories. Here we directly measure the calories assimilated by flies when maintained on full- and restricted-diets. We find that caloric intake is reduced on all diets that extend life span. Flies on low-yeast diet are long-lived and consume about half the calories of flies on high-yeast diets, regardless of the energetic content of the diet itself. Since caloric intake correlates with yeast concentration and thus with the intake of every metabolite in this dietary component, it is premature to conclude for Drosophila that calories do not explain extension of life span.

  8. Can restricting calories help you to live longer?

    PubMed

    Brown, James E

    2014-03-01

    Excess calorie consumption is associated with metabolic disorders and increased incidence of morbidity. Restricting calorie content, either by daily calorie restriction or intermittent fasting periods, has multiple benefits including weight loss and improved body composition. Previous research has shown that restricting calories in this way can increase longevity and slow the ageing process in laboratory animals, although only sparse data exist in human populations. This review critically evaluates the benefits of these dietary interventions on age-related decline and longevity.

  9. NRF2, cancer and calorie restriction

    PubMed Central

    Martín-Montalvo, A; Villalba, JM; Navas, P; de Cabo, R

    2015-01-01

    The transcription factor NF-E2-related factor (NRF2) is a key regulator of several enzymatic pathways, including cytoprotective enzymes in highly metabolic organs. In this review, we summarize the ongoing research related to NRF2 activity in cancer development, focusing on in vivo studies using NRF2 knockout (KO) mice, which have helped in defining the crucial role of NRF2 in chemoprevention. The lower cancer protection observed in NRF2 KO mice under calorie restriction (CR) suggests that most of the beneficial effects of CR on the carcinogenesis process are likely mediated by NRF2. We propose that future interventions in cancer treatment would be carried out through the activation of NRF2 in somatic cells, which will lead to a delay or prevention of the onset of some forms of human cancers, and subsequently an extension of health- and lifespan. PMID:21057541

  10. Calorie restriction and the exercise of chromatin

    PubMed Central

    Vaquero, Alejandro; Reinberg, Danny

    2009-01-01

    Since the earliest stages of evolution, organisms have faced the challenge of sensing and adapting to environmental changes for their survival under compromising conditions such as food depletion or stress. Implicit in these responses are mechanisms developed during evolution that include the targeting of chromatin to allow or prevent expression of fundamental genes and to protect genome integrity. Among the different approaches to study these mechanisms, the analysis of the response to a moderate reduction of energy intake, also known as calorie restriction (CR), has become one of the best sources of information regarding the factors and pathways involved in metabolic adaptation from lower to higher eukaryotes. Furthermore, responses to CR are involved in life span regulation—conserved from yeast to mammals—and therefore have garnered major research interest. Herein we review current knowledge of responses to CR at the molecular level and their functional link to chromatin. PMID:19608767

  11. Calorie restriction and susceptibility to intact pathogens

    PubMed Central

    2008-01-01

    Long-term calorie restriction (CR) causes numerous physiological changes that ultimately increase mean and maximum lifespan of most species examined to date. One physiological change that occurs with CR is enhanced immune function, as tested using antigens and mitogens to stimulate an immune response. Fewer studies have used intact pathogen exposure to test whether the enhanced capacity of the immune response during CR actually decreases susceptibility of hosts to their pathogens. So far, studies using intact bacteria, virus, and helminth worm exposure indicate that, despite similar or enhanced immune system function, CR hosts are more susceptible to infection by intact pathogens than their fully fed counterparts. Long-term CR studies that examine susceptibility to a variety of parasite taxa will help determine if direct CR or CR mimetics will be beneficial to people living in pathogen-rich environments. PMID:19424864

  12. Calorie Restriction and Aging in Nonhuman Primates

    PubMed Central

    Kemnitz, Joseph W.

    2012-01-01

    In the 75 years since the seminal observation of Clive McCay that restriction of calorie intake extends the lifespan of rats, a great deal has been learned about the effects of calorie restriction (CR; reduced intake of a nutritious diet) on aging in various short-lived animal models. Studies have demonstrated many beneficial effects of CR on health, the rate of aging, and longevity. Two prospective investigations of the effects of CR on long-lived nonhuman primate (NHP) species began nearly 25 years ago and are still under way. This review presents the design, methods, and main findings of these and other important contributing studies, which have generally revealed beneficial effects of CR on physiological function and the retardation of disease consistent with studies in other species. Specifically, prolonged CR appears to extend the lifespan of rhesus monkeys, which exhibited lower body fat; slower rate of muscle loss with age; lower incidence of neoplasia, cardiovascular disease, type 2 diabetes mellitus, and endometriosis; improved insulin sensitivity and glucose tolerance; and no apparent adverse effect on bone health, as well as a reduction in total energy expenditure. In addition, there are no reports of deleterious effects of CR on reproductive endpoints, and brain morphology is preserved by CR. Adrenal and thyroid hormone profiles are inconsistently affected. More research is needed to delineate the mechanisms of the desirable outcomes of CR and to develop interventions that can produce similar beneficial outcomes for humans. This research offers tremendous potential for producing novel insights into aging and risk of disease. PMID:21411859

  13. Resveratrol vs. calorie restriction: data from rodents to humans.

    PubMed

    Lam, Yan Y; Peterson, Courtney M; Ravussin, Eric

    2013-10-01

    Calorie restriction extends lifespan and confers metabolic benefits similar to the effect of lifestyle interventions. Poor compliance to long-term dietary restriction, however, hinders the success of this approach. Evidence is now persuasive for a role of resveratrol supplementation (a polyphenol in red grapes) as potential alternative to calorie restriction. This review summarizes the latest literature on the effects and the molecular mechanisms by which calorie restriction and resveratrol confer health benefits. Resveratrol activates SIRT1 and the associated improvement in energy utilization and insulin sensitivity closely resembles the benefits of calorie restriction. Current data largely support resveratrol as a potential calorie restriction mimetic to improve metabolic and probably functional health. Future studies which characterize the bioavailability and efficacy of resveratrol supplementation are critical to provide evidence for its long-term health benefits. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Calorie restriction and resveratrol in cardiovascular health and disease.

    PubMed

    Dolinsky, Vernon W; Dyck, Jason R B

    2011-11-01

    Calorie restriction is one of the most effective nutritional interventions that reproducibly protects against obesity, diabetes and cardiovascular disease. Recent evidence suggests that even when implemented over a short period, calorie restriction is a safe and effective treatment for cardiovascular disease. Herein, we review the effects of calorie restriction on the cardiovascular system as well as the biological effects of resveratrol, the most widely studied molecule that appears to mimic calorie restriction. An overview of microarray data reveals that the myocardial transcriptional effects of calorie restriction overlap with the transcriptional responses to resveratrol treatment. In addition, calorie restriction and resveratrol modulate similar pathways to improve mitochondrial function, reduce oxidative stress and increase nitric oxide production that are involved in atherosclerosis prevention, blood pressure reduction, attenuation of left-ventricular hypertrophy, resistance to myocardial ischemic injury and heart failure prevention. We also review the data that suggest that the effects of calorie restriction and resveratrol on the cardiovascular system may involve signaling through the silent information regulator of transcription (SIRT), Akt and the AMP-activated protein kinase (AMPK) pathways. While accumulating data demonstrate the health benefits of calorie restriction and resveratrol in experimental animal models, whether these interventions translate to patients with cardiovascular disease remains to be determined.

  15. Calorie restriction as an intervention in ageing

    PubMed Central

    López‐Lluch, Guillermo

    2016-01-01

    Abstract Ageing causes loss of function in tissues and organs, is accompanied by a chronic inflammatory process and affects life‐ and healthspan. Calorie restriction (CR) is a non‐genetic intervention that prevents age‐associated diseases and extends longevity in most of the animal models studied so far. CR produces a pleiotropic effect and improves multiple metabolic pathways, generating benefits to the whole organism. Among the effects of CR, modulation of mitochondrial activity and a decrease in oxidative damage are two of the hallmarks. Oxidative damage is reduced by the induction of endogenous antioxidant systems and modulation of the peroxidability index in cell membranes. Mitochondrial activity changes are regulated by inhibition of IGF‐1 and Target of Rapamycin (TOR)‐dependent activities and activation of AMP‐dependent kinase (AMPK) and the sirtuin family of proteins. The activity of PGC‐1α and FoxO is regulated by these systems and is involved in mitochondria biogenesis, oxidative metabolism activity and mitochondrial turnover. The use of mimetics and the regulation of common factors have demonstrated that these molecular pathways are essential to explain the effect of CR in the organism. Finally, the anti‐inflammatory effect of CR is an interesting emerging factor to be taken into consideration. In the present revision we focus on the general effect of CR and other mimetics in longevity, focusing especially on the cardiovascular system and skeletal muscle. PMID:26607973

  16. The Effects of Calorie Restriction in Depression and Potential Mechanisms

    PubMed Central

    Zhang, Yifan; Liu, Changhong; Zhao, Yinghao; Zhang, Xingyi; Li, Bingjin; Cui, Ranji

    2015-01-01

    Depression, also called major depressive disorder, is a neuropsychiatric disorder jeopardizing an increasing number of the population worldwide. To date, a large number of studies have devoted great attention to this problematic condition and raised several hypotheses of depression. Based on these theories, many antidepressant drugs were developed for the treatment of depression. Yet, the depressed patients are often refractory to the antidepressant therapies. Recently, increasing experimental evidences demonstrated the effects of calorie restriction in neuroendocrine system and in depression. Both basic and clinical investigations indicated that short-term calorie restriction might induce an antidepressant efficacy in depression, providing a novel avenue for treatment. Molecular basis underlying the antidepressant actions of calorie restriction might involve multiple physiological processes, primarily including orexin signaling activation, increased CREB phosphorylation and neurotrophic effects, release of endorphin and ketone production. However, the effects of chronic calorie restriction were quite controversial, in the cases that it often resulted in the long-term detrimental effects via inhibiting the function of 5-HT system and decreasing leptin levels. Here we review such dual effects of calorie restriction in depression and potential molecular basis behind these effects, especially focusing on antidepressant effects. PMID:26412073

  17. The Effects of Calorie Restriction in Depression and Potential Mechanisms.

    PubMed

    Zhang, Yifan; Liu, Changhong; Zhao, Yinghao; Zhang, Xingyi; Li, Bingjin; Cui, Ranji

    2015-01-01

    Depression, also called major depressive disorder, is a neuropsychiatric disorder jeopardizing an increasing number of the population worldwide. To date, a large number of studies have devoted great attention to this problematic condition and raised several hypotheses of depression. Based on these theories, many antidepressant drugs were developed for the treatment of depression. Yet, the depressed patients are often refractory to the antidepressant therapies. Recently, increasing experimental evidences demonstrated the effects of calorie restriction in neuroendocrine system and in depression. Both basic and clinical investigations indicated that short-term calorie restriction might induce an antidepressant efficacy in depression, providing a novel avenue for treatment. Molecular basis underlying the antidepressant actions of calorie restriction might involve multiple physiological processes, primarily including orexin signaling activation, increased CREB phosphorylation and neurotrophic effects, release of endorphin and ketone production. However, the effects of chronic calorie restriction were quite controversial, in the cases that it often resulted in the long-term detrimental effects via inhibiting the function of 5-HT system and decreasing leptin levels. Here we review such dual effects of calorie restriction in depression and potential molecular basis behind these effects, especially focusing on antidepressant effects.

  18. Calorie Restriction Attenuates Terminal Differentiation of Immune Cells

    PubMed Central

    White, Matthew J.; Beaver, Charlotte M.; Goodier, Martin R.; Bottomley, Christian; Nielsen, Carolyn M.; Wolf, Asia-Sophia F. M.; Boldrin, Luisa; Whitmore, Charlotte; Morgan, Jennifer; Pearce, Daniel J.; Riley, Eleanor M.

    2017-01-01

    Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a−CD44lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b−CD27+ cells and correspondingly lower proportions of highly differentiated CD11b+CD27−NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations. PMID:28127296

  19. Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.

    PubMed

    White, Matthew J; Beaver, Charlotte M; Goodier, Martin R; Bottomley, Christian; Nielsen, Carolyn M; Wolf, Asia-Sophia F M; Boldrin, Luisa; Whitmore, Charlotte; Morgan, Jennifer; Pearce, Daniel J; Riley, Eleanor M

    2016-01-01

    Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a(-)CD44(lo) cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b(-)CD27(+) cells and correspondingly lower proportions of highly differentiated CD11b(+)CD27(-)NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

  20. Update on Human Calorie Restriction Research123

    PubMed Central

    Roberts, Susan B.; Speakman, John

    2013-01-01

    The United States population is aging rapidly, and understanding the potential impact and feasibility of lifestyle interventions on the aging process is of central importance for addressing future population health and health care costs. This symposium addressed the question of whether caloric restriction may be a feasible strategy to improve human health by reductions in rates of primary and secondary aging in humans, viewed from the perspective of existing data in animal models, and by using emerging data from the human Comprehensive Assessment of Long-Term Reduction in Energy Intake trial, which is a randomized trial of human caloric restriction in free-living men and women. PMID:24038258

  1. Calorie restriction: is AMPK as a key sensor and effector?

    PubMed Central

    Cantó, Carles; Auwerx, Johan

    2013-01-01

    Summary Dietary restriction can extend lifespan in most organisms tested to date, suggesting that mechanisms sensing nutrient and energy availability might regulate longevity. The AMP-activated protein kinase (AMPK) has emerged as a key energy sensor with the ability to transcriptionally reprogram the cell and metabolically adapt to external cues. In this review we will discuss the possible role of AMPK in the beneficial effects of calorie restriction on health and lifespan. PMID:21841070

  2. Calorie shifting diet versus calorie restriction diet: a comparative clinical trial study.

    PubMed

    Davoodi, Sayed Hossein; Ajami, Marjan; Ayatollahi, Seyyed Abdulmajid; Dowlatshahi, Kamran; Javedan, Gholamali; Pazoki-Toroudi, Hamid Reza

    2014-04-01

    Finding new tolerable methods in weight loss has largely been an issue of interest for specialists. Present study compared a novel method of calorie shifting diet (CSD) with classic calorie restriction (CR) on weight loss in overweight and obese subjects. Seventy-four subjects (body mass index ≥25; 37) were randomized to 4 weeks control diet, 6 weeks CSD or CR diets, and 4 weeks follow-up period. CSD consisted of three phases each lasts for 2 weeks, 11 days calorie restriction which included four meals every day, and 4 h fasting between meals follow with 3 days self-selecting diet. CR subjects receive determined low calorie diet. Anthropometric and metabolic measures were assessed at different time points in the study. Four weeks after treatment, significant weight, and fat loss started (6.02 and 5.15 kg) and continued for 1 month of follow-up (5.24 and 4.3 kg), which was correlated to the restricted energy intake (P < 0.05). During three CSD phases, resting metabolic rate tended to remain unchanged. The decrease in plasma glucose, total cholesterol, and triacylglycerol were greater among subjects on the CSD diet (P < 0.05). Feeling of hunger decreased and satisfaction increased among those on the CSD diet after 4 weeks (P < 0.05). The CSD diet was associated with a greater improvement in some anthropometric measures, Adherence was better among CSD subjects. Longer and larger studies are required to determine the long-term safety and efficacy of CSD diet.

  3. Effect of calorie restriction on subjective ratings of appetite

    PubMed Central

    Anton, S. D.; Han, H.; York, E.; Martin, C. K.; Ravussin, E.; Williamson, D. A.

    2009-01-01

    Background Energy or calorie restriction (CR) has consistently been shown to produce weight loss and have beneficial health effects in numerous species, including primates and humans. Most individuals, however, are unable to sustain weight losses induced through reductions in energy intake, potentially due to increased hunger levels. The effects that prolonged CR has on subjective aspects of appetite have not been well studied. Thus, the present study tested the effect of 6 months of caloric restriction on appetite in healthy, overweight men and women. Methods Forty-eight overweight men and women with a body mass index (BMI; kg m−2) between 25–29.9 took part in a 6-month study and were randomised into one of four groups: healthy diet (control); 25% CR; 12.5% CR plus exercise (12.5% increased energy expenditure; CR + EX); low-calorie diet [LCD; 3724 kJ day−1 (890 kcal day−1) until 15% of initial body weight was lost, then maintenance]. Appetite markers (i.e. hunger, fullness, desire to eat, etc.) were assessed weekly during a fasting state. Results Body weight was significantly reduced in all three energy-restricted groups (CR = −10.4 ± 0.9%; CR + EX = −10.0 ± 0.8%; and LCD = −13.9 ± 0.7%), indicating that participants were adherent to their energy restriction regimen, whereas the healthy diet control group remained weight stable (control = −1.0 ± 1.1%). Despite these significant weight losses, appetite ratings of participants in the three energy-restricted groups at month 6 were similar to the weight stable control group. Conclusions CR regimens with low fat diets producing significant weight losses have similar effects on appetite markers over a 6-month time period compared to a weight stable control group. PMID:19302119

  4. Does calorie restriction induce mitochondrial biogenesis? A reevaluation

    PubMed Central

    Hancock, Chad R.; Han, Dong-Ho; Higashida, Kazuhiko; Kim, Sang Hyun; Holloszy, John O.

    2011-01-01

    It has been reported that 30% calorie restriction (CR) for 3 mo results in large increases in mitochondrial biogenesis in heart, brain, liver, and adipose tissue, with concomitant increases in respiration and ATP synthesis. We found these results surprising, and performed this study to determine whether 30% CR does induce an increase in mitochondria in heart, brain, liver, adipose tissue, and/or skeletal muscle. To this end, we measured the levels of a range of mitochondrial proteins, and mRNAs. With the exception of long-chain acyl-CoA dehydrogenase protein level, which was increased ∼60% in adipose tissue, none of the mitochondrial proteins or mRNAs that we measured were increased in rats subjected to 30% CR for 14 wk. There was also no increase in citrate synthase activity. Because it is not possible to have an increase in mitochondria without any increase in key mitochondrial proteins, we conclude that 30% CR does not induce an increase in mitochondria in heart, brain, liver, adipose tissue, or skeletal muscle in laboratory rodents.—Hancock, C. R., Han, D.-H., Higashida, K., Kim, S. H., Holloszy, J. O. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. PMID:21048043

  5. Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme.

    PubMed

    Maroon, Joseph; Bost, Jeffrey; Amos, Austin; Zuccoli, Giulio

    2013-08-01

    Glioblastoma multiforme is the most common malignant primary brain tumor in adults and generally considered to be universally fatal. Glioblastoma multiforme accounts for 12% to 15% of all intracranial neoplasms and affects 2 to 3 adults per every 100,000 in the United States annually. In children glioblastoma multiforme accounts for only approximately 7% to 9% of central nervous system tumors. The mean survival rate in adults after diagnosis ranges from 12 to 18 months with standard therapy and 3 to 6 months without therapy. The prognosis in children is better compared to adult tumor onset with a mean survival of approximately 4 years following gross total surgical resection and chemotherapy. There have been few advances in the treatment of glioblastoma multiforme in the past 40 years beyond surgery, radiotherapy, chemotherapy, and corticosteroids. For this reason a restrictive calorie ketogenic diet, similar to that used in children to control drug resistant seizure activity, has been advanced as an alternative adjunctive treatment to help prolonged survival. This article reviews the science of tumor metabolism and discusses the mechanism of calorie restriction, cellular energy metabolism, and how dietary induced ketosis can inhibit cancer cell's energy supply to slow tumor growth.

  6. Yeast as a model to understand the interaction between genotype and the response to calorie restriction.

    PubMed

    Schleit, Jennifer; Wasko, Brian M; Kaeberlein, Matt

    2012-08-31

    Calorie restriction is reported to enhance survival and delay the onset of age-related decline in many different species. Several proteins have been proposed to play a role in mediating the response to calorie restriction, including the target of rapamycin kinase, sirtuins, and AMP kinase. An enhanced mechanistic understanding of calorie restriction has popularized the concept of "calorie restriction mimetics", drugs that mimic the beneficial effects of caloire restriction without requiring a reduction in nutrient intake. In theory, such drugs should delay the onset and progression of multiple age-related diseases, similar to calorie restriction in mammals. Despite the potential benefits of such calorie restriction mimetics, however, relatively little is known about the interaction between genetic variation and individual response to calorie restriction. Limited evidence from model systems indicates that genotype plays a large role in determining both the magnitude and direction of effect that calorie restriction has on longevity. Here we present an overview of these data from the perspective of using yeast as a model to study aging and describe an approach we are taking to further characterize the molecular mechanisms underlying genotype-dependent responses to calorie restriction. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Sir2 and calorie restriction in yeast: a skeptical perspective.

    PubMed

    Kaeberlein, Matt; Powers, R Wilson

    2007-08-01

    Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension. This idea has been called into question with the discovery that Sir2-family proteins are not required for life span extension from CR in yeast. We present here a historical perspective and critical evaluation of the model that CR acts through Sir2 in yeast, and interpret prior reports in light of more recent discoveries. Several specific cases where the Sir2 model of CR is inconsistent with experimental data are noted. These shortcomings must be considered along with evidence supporting a role for Sir2 in CR in order to fully evaluate the validity of this model.

  8. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration.

    PubMed

    Lin, Su-Ju; Kaeberlein, Matt; Andalis, Alex A; Sturtz, Lori A; Defossez, Pierre-Antoine; Culotta, Valeria C; Fink, Gerald R; Guarente, Leonard

    2002-07-18

    Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.

  9. Resveratrol as a calorie restriction mimetic: therapeutic implications

    PubMed Central

    Chung, Jay H.; Manganiello, Vincent; Dyck, Jason R.B.

    2012-01-01

    It is widely believed that calorie restriction (CR) can extend the lifespan of model organisms and protect against aging-related diseases. A potential CR mimetic is resveratrol, which may have beneficial effects against numerous diseases such as type 2 diabetes, cardiovascular diseases, and cancer in tissue culture and animal models. However, resveratrol in its current form is not ideal as therapy, because even at very high doses it has modest efficacy and many downstream effects. Identifying the cellular targets responsible for the effects of resveratrol and developing target-specific therapies will be helpful in increasing the efficacy of this drug without increasing its potential adverse effects. A recent discovery suggests that the metabolic effects of resveratrol may be mediated by inhibiting cAMP phosphodiesterases (PDEs), particularly PDE4. Here, we review the current literature on the metabolic and cardiovascular effects of resveratrol and attempt to shed light on the controversies surrounding its action. PMID:22885100

  10. Calorie restriction and prevention of age-associated chronic disease

    PubMed Central

    Omodei, Daniela; Fontana, Luigi

    2012-01-01

    Life expectancy in the world has increased dramatically during the last century; the number of older adults is expected to rise while the number of youths will decline in the near future. This demographic shift has considerable public health and economic implications since aging is associated with the development of serious chronic diseases. Calorie restriction (CR) is the most effective nutritional intervention for slowing aging and preventing chronic disease in rodents. In non-human and human primates, CR with adequate nutrition protects against abdominal obesity, diabetes, hypertension and cardiovascular diseases. Cancer morbidity and mortality are also diminished in CR monkeys, and data obtained from individuals practicing long-term CR show a reduction of metabolic and hormonal factors associated with increased cancer risk. PMID:21402069

  11. Annual fasting; the early calories restriction for cancer prevention.

    PubMed

    Eslami, Solat; Barzgari, Zahra; Saliani, Negar; Saeedi, Nazli; Barzegari, Abolfazl

    2012-01-01

    Essentially, people's diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF) before tumor development or progress. Besides, fasting can balance the gut microbiome for enhancement of immune system against cancer formation.

  12. Calorie restriction and cancer prevention: a mechanistic perspective

    PubMed Central

    2013-01-01

    Calorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment. These CR-responsive pathways and processes represent targets for translating CR research into effective cancer prevention strategies in human beings. PMID:24280167

  13. Nutrition modulation of human aging: The calorie restriction paradigm.

    PubMed

    Das, Sai Krupa; Balasubramanian, Priya; Weerasekara, Yasoma K

    2017-11-05

    Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects of CR. Overall, the prospect for further research in both NHP and humans is highly encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Calorie restriction mimicking effects of roflumilast prevents diabetic nephropathy.

    PubMed

    Tikoo, Kulbhushan; Lodea, Saritha; Karpe, Pinakin Arun; Kumar, Sandeep

    2014-08-08

    Little is known about role of PDE4 in the development and progression of diabetic nephropathy. Here, we investigated the effect of roflumilast, a selective PDE 4 inhibitor in type 1 diabetic nephropathy. Diabetes was induced in male Sprague-Dawley rats using streptozotocin (55 mg/kg). Diabetic rats showed elevated plasma glucose, blood urea nitrogen, creatinine and decrease in plasma albumin confirming signs of nephropathy. Roflumilast at 2 and 3mg/kg normalized these alterations. Roflumilast also suppressed oxidative stress and deposition of an extracellular matrix protein such as fibronectin and collagen in kidney of diabetic rats. TUNEL assay revealed apoptosis in diabetic kidney than control and that roflumilast prevents this effect. We show that kidney of diabetic rats displayed a state of p-AMPK and SIRT1 deficiency and that roflumilast, interestingly, was able to restore their levels. Further, roflumilast prevented an increase in HO-1 and loss in the FoxO1 expression in diabetes. However, it did not improve the reduced NRF2 levels in diabetes. This is the first report to show that, like resveratrol and other SIRT1 activators, roflumilast also mimics calorie restriction effects through activation of AMPK/SIRT1 and protects against diabetic nephropathy. This study unveils the unexplored potential of roflumilast which can be used in treatment of metabolic disorders.

  15. Does calorie restriction induce mitochondrial biogenesis? A reevaluation.

    PubMed

    Hancock, Chad R; Han, Dong-Ho; Higashida, Kazuhiko; Kim, Sang Hyun; Holloszy, John O

    2011-02-01

    It has been reported that 30% calorie restriction (CR) for 3 mo results in large increases in mitochondrial biogenesis in heart, brain, liver, and adipose tissue, with concomitant increases in respiration and ATP synthesis. We found these results surprising, and performed this study to determine whether 30% CR does induce an increase in mitochondria in heart, brain, liver, adipose tissue, and/or skeletal muscle. To this end, we measured the levels of a range of mitochondrial proteins, and mRNAs. With the exception of long-chain acyl-CoA dehydrogenase protein level, which was increased ∼60% in adipose tissue, none of the mitochondrial proteins or mRNAs that we measured were increased in rats subjected to 30% CR for 14 wk. There was also no increase in citrate synthase activity. Because it is not possible to have an increase in mitochondria without any increase in key mitochondrial proteins, we conclude that 30% CR does not induce an increase in mitochondria in heart, brain, liver, adipose tissue, or skeletal muscle in laboratory rodents.

  16. Physically Active Rats Lose More Weight during Calorie Restriction

    PubMed Central

    Smyers, Mark E.; Bachir, Kailey Z.; Britton, Steven L.; Koch, Lauren G.; Novak, Colleen M.

    2014-01-01

    Daily physical activity shows substantial inter-individual variation, and low physical activity is associated with obesity and weight gain. Elevated physical activity is also associated with high intrinsic aerobic capacity, which confers considerable metabolic health benefits. Rats artificially selected for high intrinsic aerobic capacity (high-capacity runners, HCR) are more physically active than their low-capacity counterparts (low-capacity runners, LCR). To test the hypothesis that physical activity counters metabolic thriftiness, we measured physical activity and weight loss during three weeks of 50% calorie restriction (CR) in the HCR and LCR rat lines. At baseline, HCR ate more and were more active than LCR; this was seen in male rats, where LCR are considerably heavier than HCR, as well as in a set of female rats where body weight did not differ between the lines, demonstrating that this effect is consistent across sex and not secondary to body weight. We show for the first time that HCR lose more weight than LCR relative to baseline. Physical activity levels declined throughout CR, and this was more pronounced in HCR than in LCR, yet some aspects of activity remained elevated in HCR relative to LCR even during CR. This is consistent with the idea that low physical activity contributes to metabolic thriftiness during food restriction, allowing LCR to defend body mass, particularly lean mass. This has implications for physical activity during diet-induced weight loss, the genetic underpinnings of individual differences in weight loss during a diet, and the potential evolutionary opposition between metabolic thriftiness and aerobic capacity. PMID:25449411

  17. Extreme calorie restriction and energy source starvation in Saccharomyces cerevisiae represent distinct physiological states.

    PubMed

    Boender, Léonie G M; Almering, Marinka J H; Dijk, Madelon; van Maris, Antonius J A; de Winde, Johannes H; Pronk, Jack T; Daran-Lapujade, Pascale

    2011-12-01

    Cultivation methods used to investigate microbial calorie restriction often result in carbon and energy starvation. This study aims to dissect cellular responses to calorie restriction and starvation in Saccharomyces cerevisiae by using retentostat cultivation. In retentostats, cells are continuously supplied with a small, constant carbon and energy supply, sufficient for maintenance of cellular viability and integrity but insufficient for growth. When glucose-limited retentostats cultivated under extreme calorie restriction were subjected to glucose starvation, calorie-restricted and glucose-starved cells were found to share characteristics such as increased heat-shock tolerance and expression of quiescence-related genes. However, they also displayed strikingly different features. While calorie-restricted yeast cultures remained metabolically active and viable for prolonged periods of time, glucose starvation resulted in rapid consumption of reserve carbohydrates, population heterogeneity due to appearance of senescent cells and, ultimately, loss of viability. Moreover, during starvation, calculated rates of ATP synthesis from reserve carbohydrates were 2-3 orders of magnitude lower than steady-state ATP-turnover rates calculated under extreme calorie restriction in retentostats. Stringent reduction of ATP turnover during glucose starvation was accompanied by a strong down-regulation of genes involved in protein synthesis. These results demonstrate that extreme calorie restriction and carbon starvation represent different physiological states in S. cerevisiae.

  18. Calorie restriction and bone health in young, overweight individuals.

    PubMed

    Redman, Leanne M; Rood, Jennifer; Anton, Stephen D; Champagne, Catherine; Smith, Steven R; Ravussin, Eric

    2008-09-22

    Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life. Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months. Mean +/- SE body weight was reduced by -1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and -13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23% +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX, LCD, and control groups. Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health. clinicaltrials.gov Identifier: NCT00099151.

  19. Calorie Restriction and Bone Health in Young, Overweight Individuals

    PubMed Central

    Redman, Leanne M.; Rood, Jennifer; Anton, Stephen D.; Champagne, Catherine; Smith, Steven R.; Ravussin, Eric

    2009-01-01

    Background Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life. Methods Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR+EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months. Results Mean± SE body weight was reduced by -1.0% ± 1.1% (control), -10.4% ± 0.9% (CR), -10.0%±0.8% (CR+EX), and -13.9%±0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23%±10%; CR+EX, 22%±9%; and LCD, 74%±16% vs control, 4%±10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23%±10%) but were unchanged in the CR+EX, LCD, and control groups. Conclusions Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrientdense diets have no deleterious effect on bone health. PMID:18809812

  20. Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.

    PubMed

    Hord, Jeffrey M; Botchlett, Rachel; Lawler, John M

    2016-10-01

    Age-related loss of skeletal muscle mass and function, referred to as sarcopenia, is mitigated by lifelong calorie restriction as well as exercise. In aged skeletal muscle fibers there is compromised integrity of the cell membrane that may contribute to sarcopenia. The purpose of this study was to determine if lifelong mild (8%) caloric restriction (CR) and lifelong CR+voluntary wheel running (WR) could ameliorate disruption of membrane scaffolding and signaling proteins during the aging process, thus maintaining a favorable, healthy membrane environment in plantaris muscle fibers. Fischer-344 rats were divided into four groups: 24-month old adults fed ad libitum (OAL); 24-month old on 8% caloric restriction (OCR); 24month old 8% caloric restriction+wheel running (OCRWR); and 6-month old sedentary adults fed ad libitum (YAL) were used to determine age-related changes. Aging resulted in discontinuous membrane expression of dystrophin glycoprotein complex (DGC) proteins: dystrophin and α-syntrophin. Older muscle also displayed decreased content of neuronal nitric oxide synthase (nNOS), a key DGC signaling protein. In contrast, OCR and OCRWR provided significant protection against age-related DGC disruption. In conjunction with the age-related decline in membrane DGC patency, key membrane repair proteins (MG53, dysferlin, annexin A6, and annexin A2) were significantly increased in the OAL plantaris. However, lifelong CR and CRWR interventions were effective at maintaining membrane repair proteins near YAL levels of. OAL fibers also displayed reduced protein content of NADPH oxidase isoform 2 (Nox2) subunits (p67phox and p47phox), consistent with a perturbed sarcolemmal environment. Loss of Nox2 subunits was prevented by lifelong CR and CRWR. Our results are therefore consistent with the hypothesis that lifelong CR and WR are effective countermeasures against age-related alterations in the myofiber membrane environment. Copyright © 2016 Elsevier Inc. All rights

  1. Calorie Restriction Increases P-Glycoprotein and Decreases Intestinal Absorption of Digoxin in Mice

    PubMed Central

    Renaud, Helen J.; Klaassen, Curtis D.

    2016-01-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [3H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [3H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum–fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance. PMID:26744253

  2. Calorie Restriction Increases P-Glycoprotein and Decreases Intestinal Absorption of Digoxin in Mice.

    PubMed

    Renaud, Helen J; Klaassen, Curtis D; Csanaky, Iván L

    2016-03-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [(3)H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [(3)H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum-fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Calorie restriction and late-onset calorie restriction extend lifespan but do not alter protein storage in female grasshoppers

    PubMed Central

    Hatle*, John D.; Wells, Sean M.; Fuller, L. Erin; Allen, I. Cynthia; Gordy, Liza J.; Melnyk, Stephen; Quattrochi, John

    2007-01-01

    Summary Calorie restriction (CR) and late-onset CR enhance longevity in many organisms. Resource allocation theory suggests that longevity is enhanced by increasing somatic storage, at the expense of current reproduction. Phytophagous insects accumulate amino acids as hemolymph storage proteins for major developmental events. We hypothesized that protein storage is involved in life extension from CR. In a longitudinal experiment, we tested whether CR altered protein storage in female grasshoppers. Individuals on CR (60% or 70%) or late-onset CR had at least 60% greater longevity than ad libitum individuals. Age at first oviposition, dry mass of the first clutch, or lifetime fecundity were not affected by CR, but CR did increase the number of clutches produced. Most important, females on life-extending CR and late-onset CR did not differ in the concentration of hemolymph storage of proteins in comparison to ad libitum females. Protein storage changed with time in all groups, demonstrating sufficient sensitivity in our methods. Previous experiments have shown that severe CR (~30% of ad libitum) can reduce hemolymph storage. Therefore, the reduction in intake needed to extend lifespan is not sufficient to reduce protein storage in the hemolymph. These results do not support the hypothesis that protein storage is involved in life extension from CR. PMID:17049582

  4. Effects of Calorie Restriction on Cardioprotection and Cardiovascular Health

    PubMed Central

    Ahmet, Ismayil; Tae, Hyun-Jin; de Cabo, Rafael; Lakatta, Edward G.; Talan, Mark I.

    2011-01-01

    Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-mo old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-mo old AL and 29-mo old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-mo old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-mo old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-mo old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal

  5. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures

    PubMed Central

    Schafer, Marissa J.; Dolgalev, Igor; Alldred, Melissa J.; Heguy, Adriana; Ginsberg, Stephen D.

    2015-01-01

    Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months, 12.5 months of feeding) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector. PMID:26221964

  6. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway

    PubMed Central

    Hine, Christopher; Mitchell, James R.

    2015-01-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/ every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action. PMID:25523462

  7. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.

    PubMed

    Hine, Christopher; Mitchell, James R

    2015-08-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone.

    PubMed

    Speakman, J R; Mitchell, S E; Mazidi, M

    2016-12-15

    Almost exactly 100years ago Osborne and colleagues demonstrated that restricting the food intake of a small number of female rats extended their lifespan. In the 1930s experiments on the impact of diet on lifespan were extended by Slonaker, and subsequently McCay. Slonaker concluded that there was a strong impact of protein intake on lifespan, while McCay concluded that calories are the main factor causing differences in lifespan when animals are restricted (Calorie restriction or CR). Hence from the very beginning the question of whether food restriction acts on lifespan via reduced calorie intake or reduced protein intake was disputed. Subsequent work supported the idea that calories were the dominant factor. More recently, however, this role has again been questioned, particularly in studies of insects. Here we review the data regarding previous studies of protein and calorie restriction in rodents. We show that increasing CR (with simultaneous protein restriction: PR) increases lifespan, and that CR with no PR generates an identical effect. None of the residual variation in the impact of CR (with PR) on lifespan could be traced to variation in macronutrient content of the diet. Other studies show that low protein content in the diet does increase median lifespan, but the effect is smaller than the CR effect. We conclude that CR is a valid phenomenon in rodents that cannot be explained by changes in protein intake, but that there is a separate phenomenon linking protein intake to lifespan, which acts over a different range of protein intakes than is typical in CR studies. This suggests there may be a fundamental difference in the responses of insects and rodents to CR. This may be traced to differences in the physiology of these groups, or reflect a major methodological difference between 'restriction' studies performed on rodents and insects. We suggest that studies where the diet is supplied ad libitum, but diluted with inert components, should perhaps be

  9. THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE BODIES

    PubMed Central

    Maalouf, Marwan A.; Rho, Jong M.; Mattson, Mark P.

    2008-01-01

    The therapeutic potential of calorie restriction and the ketogenic diet have been repeatedly demonstrated in clinical settings and in various animal models of neurological disease. The underlying mechanisms involve an improvement in mitochondrial function, a decrease in the expression of apoptotic factors and an increase in the activity of neurotrophic factors. Clinical applications of ketogenic diets have been significantly hampered however by poor tolerability and potentially serious side-effects. Recent research aimed at identifying a mediator that can reproduce the neuroprotective effects of calorie restriction with less demanding changes to dietary intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and the underlying mechanisms are similar to those of calorie restriction and of the ketogenic diet. The present review describes the neuroprotective effects of calorie restriction, the ketogenic diet and ketone bodies and compare the molecular mechanisms of action of these interventions. PMID:18845187

  10. Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice.

    PubMed

    Wang, Da-Ting; He, Jiang; Wu, Ming; Li, Si-Ming; Gao, Qian; Zeng, Qing-Ping

    2015-01-01

    Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

  11. Mitochondria-mediated hormetic response in life span extension of calorie-restricted Saccharomyces cerevisiae.

    PubMed

    Sharma, Praveen Kumar; Agrawal, Vineet; Roy, Nilanjan

    2011-06-01

    Calorie restriction (CR) is the only proven regimen, which confers lifespan extension benefits across the various phyla right from unicellular organisms like yeast to primates. In a bid to elucidate the mechanism of calorie-restriction-mediated life span extension, the role of mitochondria in the process was investigated. In this study, we found that the mitochondrial content in CR cells remains unaltered as compared to cells grown on nonrestricted media. However, mitochondria isolated from CR cells showed increased respiration and elevated reactive oxygen species levels without augmenting adenosine triphosphate (ATP) generation. The antioxidant defense system was amplified in CR mitochondria, and in CR cells a cross protection to hydrogen-peroxide-induced stress was also observed. Moreover, we also documented that a functional electron transport chain was vital for the life span extension benefits of calorie restriction. Altogether, our results indicate that calorie restriction elicits mitohormetic effect, which ultimately leads to longevity benefit.

  12. Effects of calorie restriction on the zebrafish liver proteome

    PubMed Central

    Jury, David R.; Kaveti, Suma; Duan, Zhong-Hui; Willard, Belinda; Kinter, Michael; Londraville, Richard

    2012-01-01

    A proteomic approach was taken to study how fish respond to changes in calorie availability, with the longer-term goal of understanding the evolution of lipid metabolism in vertebrates. Zebrafish (Danio rerio) were fed either high (3 rations/day) or low (1 ration/7 days) calorie diets for 5 weeks and liver proteins extracted for proteomic analyses. Proteins were separated on two-dimensional electrophoresis gels and homologous spots compared between treatments to determine which proteins were up-regulated with high-calorie diet. Fifty-five spots were excised from the gel and analyzed via LC–ESI MS/MS, which resulted in the identification of 69 unique proteins (via multiple peptides). Twenty-nine of these proteins were differentially expressed between treatments. Differentially expressed proteins were mapped to Gene Ontology (GO) terms, and these terms compared to the entire zebrafish GO annotation set by Fisher's exact test. The most significant GO terms associated with high-calorie diet are related to a decrease in oxygen-binding activity in the high-calorie treatment. This response is consistent with a well-characterized response in obese humans, indicating there may be a link between lipid storage and hypoxia sensitivity in vertebrates. PMID:20494847

  13. Calorie restriction in overweight older adults: Do benefits exceed potential risks?

    PubMed

    Locher, Julie L; Goldsby, TaShauna U; Goss, Amy M; Kilgore, Meredith L; Gower, Barbara; Ard, Jamy D

    2016-12-15

    The evidence regarding recommendations of calorie restriction as part of a comprehensive lifestyle intervention to promote weight loss in obese older adults has remained equivocal for more than a decade. The older adult population is the fastest growing segment of the US population and a greater proportion of them are entering old age obese. These older adults require treatments based on solid evidence. Therefore the purpose of this review is three-fold: 1) to provide a more current status of the knowledge regarding recommendations of calorie restriction as part of a comprehensive lifestyle intervention to promote weight loss in obese older adults, 2) to determine what benefits and/or risks calorie restriction adds to exercise interventions in obese older adults, and 3) to consider not only outcomes related to changes in body composition, bone health, cardiometabolic disease risk, markers of inflammation, and physical function, but, also patient-centered outcomes that evaluate changes in cognitive status, quality of life, out-of-pocket costs, and mortality. Seven randomized controlled trials were identified that examined calorie restriction while controlling for exercise intervention effects. Overall, the studies found that calorie restriction combined with exercise is effective for weight loss. Evidence was mixed regarding other outcomes. The risk-benefit ratio regarding calorie restriction in older adults remains uncertain. Greater long-term follow-up is necessary, and complementary effectiveness studies are needed to identify strategies currently used by obese older adults in community settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effects of Chronic and Intermittent Calorie Restriction on Adropin Levels in Breast Cancer.

    PubMed

    Tuna, Bilge G; Atalay, Pinar B; Altunbek, Mine; Kalkan, Batuhan M; Dogan, Soner

    2017-09-18

    Adropin is a peptide hormone that has been implicated in insulin resistance and as a potential regulator of growth. The aim of this study is to determine the effect of calorie restriction on circulating levels of adropin in the MMTV-TGFα breast cancer mouse model and investigate the effects of adropin peptide on the viability of MCF-7 and MDA-231 breast cancer cells in culture. Ten-week-old mice were assigned to either ad libitum-fed (AL), chronic calorie-restricted, or intermittent calorie-restricted groups. Concentrations of serum adropin were measured using an enzyme-linked immunosorbent assay. Results showed an inverse correlation between serum adropin levels and mouse age that was attenuated by calorie restriction. In the AL group the level of adropin was significantly lower at week 50 compared to levels at week 10. However, among the calorie-restricted groups, serum levels of adropin remained high at week 50. The cell-line-specific effects were observed after treatment of cancer cell lines with a series of adropin concentrations (5, 10, 25, 50 ng/mL). Flow cytometry analysis showed that MCF-7 cells entered the early phase of apoptosis after treatment with 50 ng/mL for 24 h. Adropin may be involved in the protective effects that calorie restriction has on breast cancer risk.

  15. Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial

    PubMed Central

    Martin, Corby K.; Anton, Stephen D.; Han, Hongmei; York-Crowe, Emily; Redman, Leanne M.; Ravussin, Eric; Williamson, Donald A.

    2009-01-01

    Background Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested. Methods Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined. Results No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance. Conclusions This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases. PMID:17518698

  16. Calorie restriction aggravated cortical and trabecular bone architecture in ovariectomy-induced estrogen-deficient rats.

    PubMed

    Ahn, Hyejin; Seo, Dong-Hyun; Kim, Han Sung; Choue, Ryowon

    2014-08-01

    We hypothesized that calorie restriction (CR) and estrogen deficiency (ovariectomy [OVX]) would aggravate bone biomarkers and structural parameters in rats. Seven-week-old female Sprague-Dawley rats were randomized to sham-operated groups and fed either an ad libitum diet (SHAM-AL) or a CR diet (SHAM-CR); ovariectomy-operated groups were fed an ad libitum diet (OVX-AL) or a CR diet (OVX-CR). For 8 weeks, the OVX-AL and SHAM-AL groups were fed the same diet, whereas CR groups were fed a diet containing 50% fewer calories. Bone-related biomarkers and structural parameters (OC; deoxypyridinoline [DPD]; N-terminal telopeptide, NTx; architecture and mineralization; and microcomputed tomography images) were analyzed at the end of the experiment. The serum OC levels of calorie-restricted groups (SHAM-CR and OVX-CR) were significantly lower than those of the AL groups (SHAM-AL and OVX-AL) (P < .05). Urinary DPD levels of calorie-restricted and ovariectomized groups were higher than those of their counterparts (P < .05), whereas urinary NTx levels of calorie-restricted groups were higher than those of AL groups (P < .05). In regard to trabecular bone, the calorie-restricted and ovariectomized groups had lower values of bone volume to total volume, trabecular number, and bone mineral density, but higher values of trabecular separation than those of their counterparts (P < .05). Regarding cortical bone, the calorie-restricted groups had reduced values of bone volume, mean polar moment of inertia, and cortical thickness compared to the AL groups (P < .05). In conclusion, severe CR with or without OVX during the growth period in rats is equally detrimental to bone; CR has detrimental effects on trabecular and cortical bone; and estrogen deficiency only had an effect on trabecular bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy.

    PubMed

    Yuen, Alan W C; Sander, Josemir W

    2014-04-01

    There has been resurgence in the use of dietary treatment, principally the classical ketogenic diet and its variants, for people with epilepsy. These diets generally require significant medical and dietician support. An effective but less restrictive dietary regimen is likely to be more acceptable and more widely used. Calorie-restricted diets appear to produce a range of biochemical and metabolic changes including reduced glucose levels, reduced inflammatory markers, increased sirtuins, increased AMPK signaling, inhibition of mTOR signaling, and increase in autophagy. There are studies in animal seizure models that suggest that these biochemical and metabolic changes may decrease ictogenesis and epileptogenesis. A calorie-restricted diet might be effective in reducing seizures in people with epilepsy. Hence, there is a sufficient rationale to undertake clinical trials to assess the efficacy and safety of calorie-restricted diets in people with epilepsy.

  18. [Effects of linggui zhugan decoction combined calorie restriction on the insulin resistance of model rats and mechanisms research].

    PubMed

    Wang, Yuan-yuan; Jin, Ming-hua; Ke, Bin; Li, Su-hua; Shen, Yong-zhi; Zhai, Jia-yu; Chen, Chun-yu; Qin, Jian

    2013-03-01

    To explore the effects of Linggui Zhugan Decoction (LZD) combined calorie restriction on fasting plasma glucose (FPG), the insulin resistance (IR), and the peroxisome proliferator-activated receptor gamma (PPAR-gamma) of IR model rats. Totally 48 male Wistar rats were randomly divided into the control group, the model group, the calorie restriction group, and the TCM + calorie restriction group, 12 in each group. Ordinary forage was given to those in the control group, and high fat diet was fed to those in the rest 3 groups for 12 weeks to establish the IR model. After successful modeling, rats in the control group and the model group were continually fed with the original farage for 4 days. The normal saline at the daily dose of 20 mL/kg was given to them by gastrogavage. The normal saline at the daily dose of 20 mL/kg was given to rats in the calorie restriction group by gastrogavage after 4-day calorie restriction. LZD at the daily dose of 20 mL/kg was given to rats in the TCM +calorie restriction group by gastrogavage after 4-day calorie restriction. The body weight, FPG, serum fasting insulin (FINS), insulin resistance index (IRI), and the protein expression of PPAR-y in the omental adipose tissue were compared. After 4-day calorie restriction, the body weight obviously decreased in the calorie restriction group and the TCM +calorie restriction group, when compared with the model group (P <0.01). There was no statistical difference between the former two groups (P >0.05). The FINS and IRI obviously decreased in the calorie restriction group (P <0.01, P <0.05). The FPG, FINS, and IRI significantly decreased in the TCM + calorie restriction group (P <0. 05, P <0.01). The protein expression of PPAR-gamma obviously decreased in the calorie restriction group and the TCM + calorie restriction group (P <0.01).The phlegm dampness state was alleviated, with more significant effects shown in the TCM + calorie restriction group. LZD combined calorie restriction could

  19. Glutathione is necessary to ensure benefits of calorie restriction during ageing in Saccharomyces cerevisiae.

    PubMed

    Mannarino, Sérgio C; Amorim, Maria A; Pereira, Marcos D; Moradas-Ferreira, Pedro; Panek, Anita D; Costa, Vítor; Eleutherio, Elis C A

    2008-12-01

    Calorie restriction increases longevity of mammals and yeasts but this mechanism remains unclear. In this study, the role of glutathione on lifespan extension induced by calorie restriction was investigated by using a Saccharomyces cerevisiae strain deficient in glutathione synthesis (gsh1). We observed an increase in chronological lifespan of calorie-restricted gsh1 mutant cells, compared to WT (wild type) strain, which was associated with a reduction in the levels of oxidative stress biomarkers. The gsh1 strain showed an increase in cell yield under calorie restriction that was associated with a higher pyruvate kinase activity and a reduction in oxygen consumption and aconitase activity. This indicates that the respiratory metabolism is decreased in gsh1 mutant cells. The lifespan extension of gsh1 mutant cells did not represent an advantage at long term, since old cells of gsh1 strain showed a higher frequency of petite mutants. In addition, aged WT cells outlast aged gsh1 mutant cells in direct competition assays in a fresh medium. These results suggest that glutathione is required for the beneficial effects of calorie restriction on cellular longevity.

  20. The effects of graded levels of calorie restriction: I. impact of short term calorie and protein restriction on body composition in the C57BL/6 mouse

    PubMed Central

    Mitchell, Sharon E.; Tang, Zhanhui; Kerbois, Celine; Delville, Camille; Konstantopedos, Penelope; Bruel, Aurélie; Derous, Davina; Green, Cara; Aspden, Richard M.; Goodyear, Simon R.; Chen, Luonan; Han, Jackie J.D.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Douglas, Alex; Speakman, John R.

    2015-01-01

    Faced with reduced levels of food, animals must adjust to the consequences of the shortfall in energy. We explored how C57BL/6 mice withdrew energy from different body tissues during three months of food restriction at graded levels up to 40% (calorie restriction: CR). We compared this to the response to equivalent levels of protein restriction (PR) without a shortfall in calories. Under CR there was a dynamic change in body mass over 30 days and thereafter it stabilized. The time to reach stability was independent of the level of restriction. At the end of three months whole body dissections revealed differential utilization of the different tissues. Adipose tissue depots were the most significantly utilized tissue, and provided 55.8 to 60.9% of the total released energy. In comparison, reductions in the sizes of structural tissues contributed between 29.8 and 38.7% of the energy. The balance was made up by relatively small changes in the vital organs. The components of the alimentary tract grew slightly under restriction, particularly the stomach, and this was associated with a parallel increase in assimilation efficiency of the food (averaging 1.73%). None of the changes under CR were recapitulated by equivalent levels of PR. PMID:26079539

  1. Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction.

    PubMed

    Mayers, Jared R; Iliff, Benjamin W; Swoap, Steven J

    2009-04-01

    Dietary supplementation with resveratrol may produce calorie restriction-like effects on metabolic and longevity endpoints in mice. In this study, we sought to determine whether resveratrol treatment elicited other hallmark changes associated with calorie restriction, namely bradycardia and decreased body temperature. We found that during short-term treatment, wild-type mice on a calorie-restricted diet experienced significant decreases in both heart rate and body temperature after only 1 day whereas those receiving resveratrol exhibited no such change after 1 wk. We also used ob/ob mice to study the effects of long-term treatment because previous studies had indicated the therapeutic value of resveratrol against the linked morbidities of obesity and diabetes. After 12 wk, resveratrol treatment had produced no changes in either heart rate or body temperature. Strikingly, and in contrast to previous findings, we found that resveratrol-treated mice had significantly reduced endurance in a treadmill test. Quantitative reverse transcriptase-polymerase chain reaction suggested that a proposed target of resveratrol, Sirt1, was activated in resveratrol-treated ob/ob mice. Thus, we conclude that the bradycardia and hypothermia associated with calorie restriction occur through mechanisms unaffected by the actions of resveratrol and that further studies are needed to examine the differential effects of resveratrol in a leptin-deficient background.

  2. Calorie Restriction on Drinking Days: An Examination of Drinking Consequences among College Students

    ERIC Educational Resources Information Center

    Giles, Steven M.; Champion, Heather; Sutfin, Erin L.; McCoy, Thomas P.; Wagoner, Kim

    2009-01-01

    Objective: This study examined the association between restricting calories on intended drinking days and drunkenness frequency and alcohol-related consequences among college students. Participants: Participants included a random sample of 4,271 undergraduate college students from 10 universities. Methods: Students completed a Web-based survey…

  3. Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction.

    PubMed

    Cintron-Colon, Rigo; Sanchez-Alavez, Manuel; Nguyen, William; Mori, Simone; Gonzalez-Rivera, Ruben; Lien, Tiffany; Bartfai, Tamas; Aïd, Saba; François, Jean-Christophe; Holzenberger, Martin; Conti, Bruno

    2017-09-05

    When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrus-specific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tb regulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.

  4. Proteome adaptation of Saccharomyces cerevisiae to severe calorie restriction in Retentostat cultures.

    PubMed

    Binai, Nadine A; Bisschops, Markus M M; van Breukelen, Bas; Mohammed, Shabaz; Loeff, Luuk; Pronk, Jack T; Heck, Albert J R; Daran-Lapujade, Pascale; Slijper, Monique

    2014-08-01

    Stationary-phase, carbon-starved shake-flask cultures of Saccharomyces cerevisiae are popular models for studying eukaryotic chronological aging. However, their nutrient-starved physiological status differs substantially from that of postmitotic metazoan cells. Retentostat cultures offer an attractive alternative model system in which yeast cells, maintained under continuous calorie restriction, hardly divide but retain high metabolic activity and viability for prolonged periods of time. Using TMT labeling and UHPLC-MS/MS, the present study explores the proteome of yeast cultures during transition from exponential growth to near-zero growth in severely calorie-restricted retentostats. This transition elicited protein level changes in 20% of the yeast proteome. Increased abundance of heat shock-related proteins correlated with increased transcript levels of the corresponding genes and was consistent with a strongly increased heat shock tolerance of retentostat-grown cells. A sizable fraction (43%) of the proteins with increased abundance under calorie restriction was involved in oxidative phosphorylation and in various mitochondrial functions that, under the anaerobic, nongrowing conditions used, have a very limited role. Although it may seem surprising that yeast cells confronted with severe calorie restriction invest in the synthesis of proteins that, under those conditions, do not contribute to fitness, these responses may confer metabolic flexibility and thereby a selective advantage in fluctuating natural habitats.

  5. Calorie Restriction on Drinking Days: An Examination of Drinking Consequences among College Students

    ERIC Educational Resources Information Center

    Giles, Steven M.; Champion, Heather; Sutfin, Erin L.; McCoy, Thomas P.; Wagoner, Kim

    2009-01-01

    Objective: This study examined the association between restricting calories on intended drinking days and drunkenness frequency and alcohol-related consequences among college students. Participants: Participants included a random sample of 4,271 undergraduate college students from 10 universities. Methods: Students completed a Web-based survey…

  6. Drunkorexia: Calorie Restriction Prior to Alcohol Consumption among College Freshman

    ERIC Educational Resources Information Center

    Burke, Sloane C.; Cremeens, Jennifer; Vail-Smith, Karen; Woolsey, Conrad

    2010-01-01

    Using a sample of 692 freshmen at a southeastern university, this study examined caloric restriction among students prior to planned alcohol consumption. Participants were surveyed for self-reported alcohol consumption, binge drinking, and caloric intake habits prior to drinking episodes. Results indicated that 99 of 695 (14%) of first year…

  7. Drunkorexia: Calorie Restriction Prior to Alcohol Consumption among College Freshman

    ERIC Educational Resources Information Center

    Burke, Sloane C.; Cremeens, Jennifer; Vail-Smith, Karen; Woolsey, Conrad

    2010-01-01

    Using a sample of 692 freshmen at a southeastern university, this study examined caloric restriction among students prior to planned alcohol consumption. Participants were surveyed for self-reported alcohol consumption, binge drinking, and caloric intake habits prior to drinking episodes. Results indicated that 99 of 695 (14%) of first year…

  8. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity.

    PubMed

    Hall, Kevin D; Bemis, Thomas; Brychta, Robert; Chen, Kong Y; Courville, Amber; Crayner, Emma J; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Knuth, Nicolas D; Miller, Bernard V; Prado, Carla M; Siervo, Mario; Skarulis, Monica C; Walter, Mary; Walter, Peter J; Yannai, Laura

    2015-09-01

    Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Calorie for calorie, dietary fat restriction results in more body fat loss than carbohydrate restriction in people with obesity

    PubMed Central

    Hall, Kevin D.; Bemis, Thomas; Brychta, Robert; Chen, Kong Y.; Courville, Amber; Crayner, Emma J.; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Knuth, Nicolas D.; Miller, Bernard V.; Prado, Carla M.; Siervo, Mario; Skarulis, Monica C.; Walter, Mary; Walter, Peter J.; Yannai, Laura

    2015-01-01

    Summary Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5 day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53±6 g/d of body fat, fat oxidation was unchanged by fat restriction leading to 89±6 g/d of fat loss and was significantly greater than carbohydrate restriction (p=0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with isocaloric diets varying in carbohydrate and fat. PMID:26278052

  10. Metabolic Aspects of Caloric Restriction (500 Calories): Body Composition Changes.

    DTIC Science & Technology

    1979-08-01

    liquid diets; Body weight losses; Body fat losses; Dry protein changes; Skinfold thicknesses ; Deuterium dilution; 4 OK counting; Body volumes and...indicates the water sparing and fat utilizing effects of limited carbohydrate and protein with mineral supplementation. The skinfold thicknesses of...The skinfold thicknesses of both groups were also decreased during * caloric restriction. Lesser changes were noted when minerals were in- cluded in

  11. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity.

    PubMed

    Testa, Gabriella; Biasi, Fiorella; Poli, Giuseppe; Chiarpotto, Elena

    2014-01-01

    Improvements in health care have increased human life expectancy in recent decades, and the elderly population is thus increasing in most developed countries. Unfortunately this still means increased years of poor health or disability. Since it is not yet possible to modify our genetic background, the best anti-aging strategy is currently to intervene on environmental factors, aiming to reduce the incidence of risk factors of poor health. Calorie restriction (CR) with adequate nutrition is the only non-genetic, and the most consistent non-pharmacological intervention that extends lifespan in model organisms from yeast to mammals, and protects against the deterioration of biological functions, delaying or reducing the risk of many age-related diseases. The biological mechanisms of CR's beneficial effects include modifications in energy metabolism, oxidative stress, insulin sensitivity, inflammation, autophagy, neuroendocrine function and induction of hormesis/xenohormesis response. The molecular signalling pathways mediating the anti-aging effect of CR include sirtuins, peroxisome proliferator activated receptor G coactivator-1α, AMP-activated protein kinase, insulin/insulin growth factor-1, and target of rapamycin, which form a pretty interacting network. However, most people would not comply with such a rigorous dietary program; research is thus increasingly aimed at determining the feasibility and efficacy of natural and/or pharmacological CR mimetic molecules/ treatments without lowering food intake, particularly in mid- to late-life periods. Likely candidates act on the same signalling pathways as CR, and include resveratrol and other polyphenols, rapamycin, 2-deoxy-D-glucose and other glycolytic inhibitors, insulin pathway and AMP-activated protein kinase activators, autophagy stimulators, alpha-lipoic acid, and other antioxidants.

  12. Combination of intermittent calorie restriction and eicosapentaenoic acid for inhibition of mammary tumors.

    PubMed

    Mizuno, Nancy K; Rogozina, Olga P; Seppanen, Christine M; Liao, D Joshua; Cleary, Margot P; Grossmann, Michael E

    2013-06-01

    There are a number of dietary interventions capable of inhibiting mammary tumorigenesis; however, the effectiveness of dietary combinations is largely unexplored. Here, we combined 2 interventions previously shown individually to inhibit mammary tumor development. The first was the use of the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the second was the implementation of calorie restriction. MMTV-Her2/neu mice were used as a model for human breast cancers, which overexpress Her2/neu. Six groups of mice were enrolled. Half were fed a control (Con) diet with 10.1% fat calories from soy oil, whereas the other half consumed a diet with 72% fat calories from EPA. Within each diet, mice were further divided into ad libitum (AL), chronic calorie-restricted (CCR), or intermittent calorie-restricted (ICR) groups. Mammary tumor incidence was lowest in ICR-EPA (15%) and highest in AL-Con mice (87%), whereas AL-EPA, CCR-Con, CCR-EPA, and ICR-Con groups had mammary tumor incidence rates of 63%, 47%, 40%, and 59%, respectively. Survival was effected similarly by the interventions. Consumption of EPA dramatically reduced serum leptin (P < 0.02) and increased serum adiponectin in the AL-EPA mice compared with AL-Con mice (P < 0.001). Both CCR and ICR decreased serum leptin and insulin-like growth factor I (IGF-I) compared with AL mice but not compared with each other. These results illustrate that mammary tumor inhibition is significantly increased when ICR and EPA are combined as compared with either intervention alone. This response may be related to alterations in the balance of serum growth factors and adipokines.

  13. Following a calorie-restricted diet may help in reducing healthcare students' fat-phobia.

    PubMed

    Cotugna, Nancy; Mallick, Anum

    2010-06-01

    Data from National Health and Nutrition Examination Survey 2005/2006 show that 32.7% of US adults are overweight (BMI 25.0-29.9), 34.3% are obese (BMI 30-39.9), and 5.9% are extremely obese (BMI >or= 40). For the first time, the number of obese American adults is greater than those who are merely overweight. Negative attitudes and fat phobia toward the overweight exist not only in the general population, but also among health professionals including dietitians and dietetics students. The purpose of this study was to determine if fat phobia might be reduced among future professionals by putting students on a calorie-restricted diet for a short period. Forty dietetics and health promotion students enrolled in a university obesity course completed the Fat Phobia Scale test before and after following a calorie restricted diet for 1 week (1,200 calories and 1,500 calories for women and men, respectively). Students also reflected their thoughts about following such a diet via brief journal entries. Results showed the change in fat phobias after following a calorie-restricted diet was significant. Many journal entries reflected a newfound respect for individuals struggling to lose weight and change in prior negative attitudes. Students reported that this experience would impact their future dealings with overweight/obese clients. It may be useful to incorporate this type of activity into the training of nutrition and other health professional students to increase sensitivity and reduce existing biases and negative attitudes toward overweight/obese clients.

  14. The effects of graded levels of calorie restriction: VIII. Impact of short term calorie and protein restriction on basal metabolic rate in the C57BL/6 mouse

    PubMed Central

    Mitchell, Sharon E.; Tang, ZhanHui; Kerbois, Celine; Delville, Camille; Derous, Davina; Green, Cara L.; Wang, Yingchun; Han, Jackie J.D.; Chen, Luonan; Douglas, Alex; Lusseau, David; Promislow, Daniel E.L.; Speakman, John R.

    2017-01-01

    Under calorie restriction (CR) animals need to lower energy demands. Whether this involves a reduction in cellular metabolism is an issue of contention. We exposed C57BL/6 mice to graded CR for 3 months, measured BMR and dissected out 20 body compartments. From a separate age-matched group (n=57), we built 7 predictive models for BMR. Unadjusted BMR declined with severity of restriction. Comparison of measured and predicted BMR from the simple models suggested suppression occurred. The extent of suppression was greater with increased CR severity. However, when models based on individual organ sizes as predictors were used, the discrepancy between the prediction and the observed BMR disappeared. This suggested metabolic suppression was an artefact of not having a detailed enough model to predict the expected changes in metabolism. Our data have wide implications because they indicate that inferred metabolic impacts of genetic and other manipulations may reflect effects on organ morphology. PMID:28193912

  15. Cyclic AMP Mimics the Anti-ageing Effects of Calorie Restriction by Up-Regulating Sirtuin.

    PubMed

    Wang, Zhuoran; Zhang, Lu; Liang, Yaru; Zhang, Chi; Xu, Zhiyu; Zhang, Lang; Fuji, Ryosuke; Mu, Wei; Li, Liyuan; Jiang, Junjun; Ju, Yong; Wang, Zhao

    2015-07-08

    Cyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger, and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases.

  16. CALORIE RESTRICTION MODIFIES UBIQUINONE AND COQ TRANSCRIPTS LEVELS IN MOUSE TISSUES

    PubMed Central

    Parrado, Cristina; López-Lluch, Guillermo; Rodríguez-Bies, Elisabet; Santa-Cruz, Sara; Navas, Plácido; Ramsey, Jon J.; Villalba, José M.

    2011-01-01

    We studied ubiquinone (Q), Q homologue ratio and steady-state levels of mCOQ transcripts in tissues from mice fed ad libitum or under calorie restriction. Maximum ubiquinone levels on a protein basis were found in kidney and heart, followed by liver, brain and skeletal muscle. Liver and skeletal muscle showed the highest Q9/Q10 ratios with significant inter-individual variability. Heart, kidney, and particularly brain exhibited lower Q9/Q10 ratios and inter-individual variability. In skeletal muscle and heart, the most abundant mCOQ transcript was mCOQ7, followed by mCOQ8, mCOQ2, mPDSS2, mPDSS1 and mCOQ3. In non muscular tissues (liver, kidney and brain) the most abundant mCOQ transcript was mCOQ2, followed by mCOQ7, mCOQ8, mPDSS1, mPDSS2, and mCOQ3. Calorie restriction increased both ubiquinone homologues and mPDSS2 mRNA in skeletal muscle, but mCOQ7 was decreased. In contrast, Q9 and most mCOQ transcripts were decreased in heart. Calorie restriction also modified Q9/Q10 ratio, which was increased in kidney and decreased in heart without alterations of mPDSS1 or mPDSS2 transcripts. We demonstrate for the first time that unique patterns of mCOQ transcripts exist in muscular and non-muscular tissues, and that Q and COQ genes are targets of calorie restriction in a tissue-specific way. PMID:21447381

  17. Dietary Fat and Aging Modulate Apoptotic Signaling in Liver of Calorie-Restricted Mice

    PubMed Central

    López-Domínguez, José Alberto; Khraiwesh, Husam; González-Reyes, José Antonio; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon Jay; de Cabo, Rafael; Burón, María Isabel

    2015-01-01

    Imbalance between proliferation and cell death accounts for several age-linked diseases. Aging, calorie restriction (CR), and fat source are all factors that may influence apoptotic signaling in liver, an organ that plays a central metabolic role in the organism. Here, we have studied the combined effect of these factors on a number of apoptosis regulators and effectors. For this purpose, animals were fed diets containing different fat sources (lard, soybean oil, or fish oil) under CR for 6 or 18 months. An age-linked increase in the mitochondrial apoptotic pathway was detected with CR, including a decrease in Bcl-2/Bax ratio, an enhanced release of cytochrome c to the cytosol and higher caspase-9 activity. However, these changes were not fully transmitted to the effectors apoptosis-inducing factor and caspase-3. CR (which abated aging-related inflammatory responses) and dietary fat altered the activities of caspases-8, -9, and -3. Apoptotic index (DNA fragmentation) and mean nuclear area were increased in aged animals with the exception of calorie-restricted mice fed a lard-based fat source. These results suggest possible protective changes in hepatic homeostasis with aging in the calorie-restricted lard group. PMID:24691092

  18. Combined effects of short-term calorie restriction and exercise on insulin action in normal rats.

    PubMed

    Jiang, H Y; Koike, T; Li, P; Wang, Z H; Kawata, Y; Oshida, Y

    2010-12-01

    The present study examined the effect of combination of short-term calorie restriction (CR) and moderate exercise on insulin action in normal rats. Rats were divided randomly into 4 groups: ad libitum, sedentary (A-Sed); calorie restriction, sedentary (CR-Sed); ad libitum, exercise (A-Ex); and calorie restriction, exercise (CR-Ex). Rats in the exercise groups were run on a rodent treadmill. Rats in the CR groups were fed every alternate day. Oral glucose tolerance test (OGTT) showed improvements in both CR-Sed and A-Ex groups compared with the A-Sed group; no further improvement in glucose tolerance was observed in the CR-Ex group. In contrast, glucose infusion rates (GIRs) determined by the hyperinsulinemic-euglycemic clamp method indicated that the GIR of the CR and exercise combination was significantly better than that of the sole intervention of CR or exercise. There was no difference in the levels of fasting glucose, insulin, or high-molecular weight forms of adiponectin among the 4 groups. Protein expression of GLUT-4 in the skeletal muscle increased by exercise, but not by CR. Our findings indicate that the combination of exercise and CR may be effective in enhancing insulin sensitivity at the skeletal muscle in normal subjects. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Calorie restriction up-regulates iron and copper transport genes in Saccharomyces cerevisiae.

    PubMed

    Sharma, Praveen Kumar; Mittal, Nitish; Deswal, Sumit; Roy, Nilanjan

    2011-02-01

    Calorie restriction (CR) is a non genetic intervention, known to confer longevity benefits across the various phyla from unicellular yeast to mammals. CR also invokes homeostatic responses similar to stress, however the sequence of molecular events leading to longevity is still illusive. In this study, we analysed the whole genome gene expression profile in response to CR, mutations mimicking CR, heat shock and H(2)O(2) from a gene ontology perspective. Our analysis revealed that mitochondrion is a common hub in the gene expression programme under these conditions and the electron transport chain (ETC) is a major player. Consequently the genes involved in the metal ion transport were also significantly up-regulated. We confirmed the results of the in silico analysis using quantitative real time PCR which showed up-regulation of genes involved in respiration and transport of iron and copper. The promoter activity of one of the representative genes, FET3, was also found to be higher upon calorie restriction. Altogether, our results indicate that upon calorie restriction the levels of iron and copper fall in cells, which elicits a transcriptional response up-regulating the genes involved in their uptake to maintain cellular homeostasis.

  20. Clues to Maintaining Calorie Restriction? Psychosocial Profiles of Successful Long-term Restrictors

    PubMed Central

    Incollingo Belsky, Angela C.; Epel, Elissa S.; Tomiyama, A. Janet

    2014-01-01

    To combat the obesity epidemic, interventions and treatment often recommend low-calorie dieting. Calorie restriction (CR) as a weight intervention, however, is often unsuccessful, as most people cannot sustain the behavior. Yet one small group has maintained extreme CR over years—members of the CR Society and followers of The CR Way. This study examined stable psychosocial characteristics of these individuals to identify traits that may promote success at long-term CR. In 65 participants, we measured diet, eating behaviors, and personality traits comparing calorie restrictors to two age-, gender-, ethnicity-, and education-matched comparison groups (normal weight and overweight/obese). We first tested whether the CR group restricted calories without indications of eating disorder pathology, and second, what crystallized psychosocial characteristics set them apart from their non-restricting comparisons. Results indicated the CR group averaged 10 years of CR but scored lower than comparison groups on measures of disordered eating (p < .001) and psychopathology (p < .001). Particularly against overweight/obese participants, CR participants scored lower on neuroticism (p < .04) and hostility (p < .01), and were stronger in future time orientation (p< .05). Overall, CR profiles reflected high self-control and well being, except for having few close relationships. This study suggests a potential predisposition for successful long-term CR without disordered eating. Since modifying trait factors may be unrealistic, there may be psychosocial boundaries to the capacity for sustaining CR. Paralleling a movement towards personalized medicine, this study points toward a personalized behavioral medicine model in behavioral nutrition and treatment of overweight/obesity. PMID:24747211

  1. Dietary fat modifies mitochondrial and plasma membrane apoptotic signaling in skeletal muscle of calorie-restricted mice.

    PubMed

    López-Domínguez, José Alberto; Khraiwesh, Husam; González-Reyes, José Antonio; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon Jay; de Cabo, Rafael; Burón, María Isabel; Villalba, José M

    2013-12-01

    Calorie restriction decreases skeletal muscle apoptosis, and this phenomenon has been mechanistically linked to its protective action against sarcopenia of aging. Alterations in lipid composition of membranes have been related with the beneficial effects of calorie restriction. However, no study has been designed to date to elucidate if different dietary fat sources with calorie restriction modify apoptotic signaling in skeletal muscle. We show that a 6-month calorie restriction decreased the activity of the plasma membrane neutral sphingomyelinase, although caspase-8/10 activity was not altered, in young adult mice. Lipid hydroperoxides, Bax levels, and cytochrome c and AIF release/accumulation into the cytosol were also decreased, although caspase-9 activity was unchanged. No alterations in caspase-3 and apoptotic index (DNA fragmentation) were observed, but calorie restriction improved structural features of gastrocnemius fibers by increasing cross-sectional area and decreasing circularity of fibers in cross sections. Changing dietary fat with calorie restriction produced substantial alterations of apoptotic signaling. Fish oil augmented the protective effect of calorie restriction decreasing plasma membrane neutral sphingomyelinase, Bax levels, caspase-8/10, and -9 activities, while increasing levels of the antioxidant coenzyme Q at the plasma membrane, and potentiating the increase of cross-sectional area and the decrease of fiber circularity in cross sections. Many of these changes were not found when we used lard. Our data support that dietary fish oil with calorie restriction produces a cellular anti-apoptotic environment in skeletal muscle with a downregulation of components involved in the initial stages of apoptosis engagement, both at the plasma membrane and the mitochondria.

  2. Sir-2.1 modulates 'calorie-restriction-mediated' prevention of neurodegeneration in Caenorhabditis elegans: implications for Parkinson's disease.

    PubMed

    Jadiya, Pooja; Chatterjee, Manavi; Sammi, Shreesh Raj; Kaur, Supinder; Palit, Gautam; Nazir, Aamir

    2011-09-23

    The phenomenon of aging is known to modulate many disease conditions including neurodegenerative ailments like Parkinson's disease (PD) which is characterized by selective loss of dopaminergic neurons. Recent studies have reported on such effects, as calorie restriction, in modulating aging in living systems. We reason that PD, being an age-associated neurodegenerative disease might be modulated by interventions like calorie restriction. In the present study we employed the transgenic Caenorhabditis elegans model (P(dat-1)::GFP) expressing green fluorescence protein (GFP) specifically in eight dopaminergic (DA) neurons. Selective degeneration of dopaminergic neurons was induced by treatment of worms with 6-hydroxy dopamine (6-OHDA), a selective catecholaminergic neurotoxin, followed by studies on effect of calorie restriction on the neurodegeneration. Employing confocal microscopy of the dopaminergic neurons and HPLC analysis of dopamine levels in the nematodes, we found that calorie restriction has a preventive effect on dopaminergic neurodegeneration in the worm model. We further studied the role of sirtuin, sir-2.1, in modulating such an effect. Studies employing RNAi induced gene silencing of nematode sir-2.1, revealed that presence of Sir-2.1 is necessary for achieving the protective effect of calorie restriction on dopaminergic neurodegeneration. Our studies provide evidence that calorie restriction affords, an sir-2.1 mediated, protection against the dopaminergic neurodegeneration, that might have implications for neurodegenerative Parkinson's disease.

  3. Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging.

    PubMed

    Rangaraju, Sunitha; Hankins, David; Madorsky, Irina; Madorsky, Evgenia; Lee, Wei-Hua; Carter, Christy S; Leeuwenburgh, Christiaan; Notterpek, Lucia

    2009-04-01

    Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo. Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy-lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health.

  4. The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

    PubMed Central

    Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

    2016-01-01

    Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

  5. The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

    PubMed

    Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

    2016-04-01

    Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

  6. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

    PubMed Central

    Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

    2016-01-01

    Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

  7. Leucine improves protein nutritional status and regulates hepatic lipid metabolism in calorie-restricted rats.

    PubMed

    Pedroso, João Alfredo B; Nishimura, Luciana Sigueta; de Matos-Neto, Emídio Marques; Donato, Jose; Tirapegui, Julio

    2014-06-01

    Several studies have highlighted the potential of leucine supplementation for the treatment of metabolic diseases including type 2 diabetes and obesity. Caloric restriction is a common approach to improve the health in diabetic and obese subjects. However, very few studies assessed the effects of leucine supplementation in calorie-restricted animals. Rats were subjected to a 30% calorie-restricted diet for 6 weeks to study the effects of leucine supplementation on protein status markers and lipid metabolism. Caloric restriction reduced the body weight. However, increased leucine intake preserved body lean mass and protein mass and improved protein anabolism as indicated by the increased circulating levels of albumin and insulin-like growth factor-1 (IGF-1), and the liver expression of albumin and IGF-1 messenger RNA. Leucine supplementation also increased the circulating levels of interleukin-6 and leptin but did not affect the tumour necrosis factor-α and monocyte chemotactic protein-1 concentrations. Ketone bodies were increased in rats consuming a leucine-rich diet, but we observed no changes in cholesterol or triglycerides concentrations. Caloric restriction reduced the liver expression of peroxisome proliferator activated receptor-α and glucose-6-phosphatase, whereas leucine supplementation increased the liver expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) reductase and sterol regulatory element-binding transcription factor 1. A leucine-rich diet during caloric restriction preserved whole body protein mass and improved markers of protein anabolism. In addition, leucine modulated the hepatic lipid metabolism. These results indicate that increased leucine intake may be useful in preventing excessive protein waste in conditions of large weight loss.

  8. Effect of Chronic and Intermittent Calorie Restriction on Serum Adiponectin and Leptin and Mammary Tumorigenesis

    PubMed Central

    Rogozina, Olga P.; Bonorden, Melissa J.L.; Seppanen, Christine N.; Grande, Joseph P.; Cleary, Margot P.

    2011-01-01

    The effect of chronic (CCR) and intermittent (ICR) caloric restriction on serum adiponectin and leptin levels was investigated in relation to mammary tumorigenesis. 10-wks old MMTV-TGF-α female mice were assigned to ad libitum-fed (AL) (AIN-93M diet), ICR (3-wks 50% caloric restriction, AIN-93M–mod diet, 2x protein, fat, vitamins, and minerals followed by 3-wks 100% AL consumption of AIN-93M), and CCR (calorie and nutrient intake matched for each 6-wks ICR cycle, ∼75% of AL) groups. Mice were sacrificed at 79 (end of restriction) or 82 (end of refeeding) wks of age. Serum was obtained in cycles 1, 3, 5, 8, 11 and terminal. Mammary tumor incidence was 71.0%, 35.4%, and 9.1% for AL, CCR and ICR mice, respectively. Serum adiponectin levels were similar among groups with no impact of either CCR or ICR. Serum leptin level rose in AL mice with increasing age but was significantly reduced by long-term CCR and ICR. The ICR protocol was also associated with an elevated adiponectin:leptin ratio. In addition, ICR-Restricted mice had increased mammary tissue AdipoR1 expression and decreased leptin and ObRb expression compared to AL mice. Mammary fat pads from tumor-free ICR-mice had higher adiponectin expression than AL and CCR mice while all tumor-bearing mice had weak adiponectin signal in mammary fat pad. Although we did not demonstrate an association of either adiponectin or leptin with individual mice in relation to mammary tumorigenesis, we did find that reduced serum leptin and elevated adiponectin:leptin ratio were associated with the protective effect of intermittent calorie restriction. PMID:21257708

  9. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

    PubMed Central

    Margolis, Lee M.; Rivas, Donato A.; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J.; McClung, James P.; Fielding, Roger A.; Pasiakos, Stefan M.

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  10. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

    PubMed Central

    McKiernan, Susan H.; Colman, Ricki J.; Aiken, Erik; Evans, Trent D.; Beasley, T.Mark; Aiken, Judd M.; Weindruch, Richard; Anderson, Rozalyn M.

    2012-01-01

    We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27–33yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16–22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETSab), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETSab fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals. PMID:22226624

  11. Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans

    PubMed Central

    Soare, Andreea; Cangemi, Roberto; Omodei, Daniela; Holloszy, John O.; Fontana, Luigi

    2011-01-01

    Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7±9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769±348 kcal/d) than in the WD (2302±668 kcal/d) and EX (2798±760 kcal/d) groups (P<0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P≤0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging. PMID:21483032

  12. Interactions between light, mealtime and calorie restriction to control daily timing in mammals.

    PubMed

    Challet, Etienne

    2010-06-01

    Daily variations in behaviour and physiology are controlled by a circadian timing system consisting of a network of oscillatory structures. In mammals, a master clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, adjusts timing of other self-sustained oscillators in the brain and peripheral organs. Synchronisation to external cues is mainly achieved by ambient light, which resets the SCN clock. Other environmental factors, in particular food availability and time of feeding, also influence internal timing. Timed feeding can reset the phase of the peripheral oscillators whilst having almost no effect in shifting the phase of the SCN clockwork when animals are exposed (synchronised) to a light-dark cycle. Food deprivation and calorie restriction lead not only to loss of body mass (>15%) and increased motor activity, but also affect the timing of daily activity, nocturnal animals becoming partially diurnal (i.e. they are active during their usual sleep period). This change in behavioural timing is due in part to the fact that metabolic cues associated with calorie restriction affect the SCN clock and its synchronisation to light.

  13. Effect of calorie restriction and refeeding on skin wound healing in the rat.

    PubMed

    Hunt, Nicole D; Li, Garrick D; Zhu, Min; Miller, Marshall; Levette, Andrew; Chachich, Mark E; Spangler, Edward L; Allard, Joanne S; Hyun, Dong-Hoon; Ingram, Donald K; de Cabo, Rafael

    2012-12-01

    Calorie restriction (CR) is a reliable anti-aging intervention that attenuates the onset of a number of age-related diseases, reduces oxidative damage, and maintains function during aging. In the current study, we assessed the effects of CR and other feeding regimens on wound healing in 7-month-old Fischer-344 rats from a larger cohort of rats that had been fed either ad libitum (AL) or 40% calorie restricted based on AL consumption. Rats were assigned to one of three diet groups that received three skin punch wounds along the dorsal interscapular region (12-mm diameter near the front limbs) of the back as follows: (1) CR (n = 8) were wounded and maintained on CR until they healed, (2) AL (n = 5) were wounded and maintained on AL until wound closure was completed, and (3) CR rats were refed (RF, n = 9) AL for 48 h prior to wounding and maintained on AL until they healed. We observed that young rats on CR healed more slowly while CR rats refed for 48 h prior to wounding healed as fast as AL fed rats, similar to a study reported in aged CR and RF mice (Reed et al. 1996). Our data suggest that CR subjects, regardless of age, fail to heal well and that provision of increased nutrition to CR subjects prior to wounding enhances the healing process.

  14. Modulation of sphingolipid metabolism with calorie restriction enhances insulin action in skeletal muscle

    PubMed Central

    Obanda, Diana N.; Yu, Yongmei; Wang, Zhong Q; Cefalu, William T.

    2015-01-01

    This study sought to investigate the effect of calorie restriction (CR) on skeletal muscle sphingolipid metabolism and its contribution to improved insulin action in rats after a 6 month feeding study. Twenty nine (29) male Fischer-344 rats were randomized to an ad libitum (AL) diet or 30% CR. Dietary intake, body weight, and insulin sensitivity were monitored. After 6 months, skeletal muscle (vastus lateralis) was obtained for insulin signaling and lipid profiling. Calorie restriction significantly decreased insulin and glucose levels and also altered the expression and activity of proteins involved in sphingolipid formation and metabolism. The quantities of ceramides significantly increased in CR animals (p<0.05; n=14–15), while ceramide metabolism products (i.e glycosphingolipids: hexosylceramides and lactosylceramides) significantly decreased (p<0.05; n=14–15). Ceramide phosphates, sphingomyelins, sphingosine and sphingosine phosphate were not significantly different between AL and CR groups (p=ns; n=14–15). Lactosylceramide quantities correlated significantly with surrogate markers of insulin resistance (HOMA-IR) (r=0.7, p<0.005). Products of ceramide metabolism (glycosphingolipids), known to interfere with insulin signaling at elevated levels were significantly reduced in the skeletal muscle of CR animals. The increase in insulin sensitivity is associated with glycosphingolipid levels. PMID:25771159

  15. Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans.

    PubMed

    Soare, Andreea; Cangemi, Roberto; Omodei, Daniela; Holloszy, John O; Fontana, Luigi

    2011-04-01

    Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7 ± 9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769 ± 348 kcal/d) than in the WD (2302 ± 668 kcal/d) and EX (2798 ± 760 kcal/d) groups (P < 0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P ≤ 0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging.

  16. Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans).

    PubMed

    Blagosklonny, Mikhail V

    2010-02-15

    Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging. Humans are not an exception and CR must increase both maximal and healthy lifespan in humans to the same degree as it does in other mammals. Unlike mice, however, humans benefit from medical care, which prolongs lifespan despite accelerated aging in non-restricted individuals. Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?

  17. One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents.

    PubMed

    Ruiz, Alicia; Cerdó, Tomás; Jáuregui, Ruy; Pieper, Dietmar H; Marcos, Ascensión; Clemente, Alfonso; García, Federico; Margolles, Abelardo; Ferrer, Manuel; Campoy, Cristina; Suárez, Antonio

    2017-04-01

    Recent evidence has disclosed a connection between gut microbial glycosidase activity and adiposity in obese. Here, we measured microbial α-glucosidase and β-galactosidase activities and sorted fluorescently labeled β-galactosidase containing (βGAL) microorganisms in faecal samples of eight lean and thirteen obese adolescents that followed a controlled calorie restriction program during one year. β-galactosidase is a highly distributed functional trait, mainly expressed by members of Blautia, Bacteroides, Alcaligenes, Acinetobacter and Propionibacterium. Only long-term calorie restriction induced clear changes in the microbiota of obese adolescents. Long-term calorie restriction induced significant shifts in total and βGAL gut microbiota, reducing the Firmicutes:Bacteroidetes ratio and enhancing the growth of beneficial microorganisms such as Bacteroides, Roseburia, Faecalibacterium and Clostridium XIVa. Moreover, the structure and composition of βGAL community in obese after long-term calorie restriction was highly similar to that of lean adolescents. However, despite this high compositional similarity, microbial metabolic performance was different, split in two metabolic states at a body mass index value of 25. Our study shows that calorie restriction is a strong environmental force reshaping gut microbiota though its metabolic performance is linked to host's adiposity, suggesting that functional redundancy and metabolic plasticity are fundamental properties of gut microbial ecosystem. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  18. Alterations in Hepatic Glucose and Energy Metabolism as a Result of Calorie and Carbohydrate Restriction

    PubMed Central

    Browning, Jeffrey D.; Weis, Brian; Davis, Jeannie; Satapati, Santhosh; Merritt, Matthew; Malloy, Craig R.; Burgess, Shawn C.

    2009-01-01

    Carbohydrate-restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis and ketosis. Because little is known regarding the effect of carbohydrate-restriction on the origin of gluconeogenic precursors (gluconeogenesis from glycerol (GNGglycerol) and lactate/amino acids (GNGPEP)) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used 2H and 13C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and TCA cycle flux in weight-stable subjects(n=7) and subjects following carbohydrate-(n=7) or calorie-restriction(n=7). The majority of hepatic glucose production in carbohydrate-restricted subjects came from GNGPEP. The contribution of glycerol to gluconeogenesis was similar in all groups despite evidence of increased fat oxidation in carbohydrate-restricted subjects. A strong correlation between TCA cycle flux and GNGPEP was found, though the reliance on TCA cycle energy production for gluconeogenesis was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of gluconeogenesis. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNGPEP is maximal. In conclusion, carbohydrate-restriction modifies hepatic gluconeogenesis by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic β-oxidation. PMID:18925642

  19. Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?

    PubMed

    Varady, K A

    2011-07-01

    Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15-60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4-8%, 11-16%, respectively) and daily CR (5-8%, 10-20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.

  20. Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction.

    PubMed

    Varady, Krista A; Allister, Candice A; Roohk, Donald J; Hellerstein, Marc K

    2010-03-01

    Calorie restriction (CR) and alternate-day fasting (ADF) beneficially affect several aspects of adipose tissue physiology, but direct comparisons between regimens have yet to be performed. The present study evaluated the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and examined the kinetic mechanisms that underlie changes in fat distribution. Thirty female C57BL/6J mice were randomized to one of five groups for 4 weeks: (a) CR-25% (25% energy restriction daily), (b) ADF-75% (75% restriction on fast day), (c) ADF-85% (85% restriction on fast day), (d) ADF-100% (100% restriction on fast day) and (e) control (ad libitum fed). Body weights of the CR mice were lower than that of the ADF and control groups posttreatment. After 4 weeks of diet, the proportion of visceral fat decreased (P<.001) and the proportion of subcutaneous fat increased (P<.001) similarly in ADF and CR animals. Adiponectin increased (P<.05) by 62-86% in the ADF groups and by 69% in the CR group. Triglyceride (TG) synthesis and de novo lipogenesis were augmented (P<.05) in the subcutaneous fat pad of ADF and CR animals, relative to control. No differences in net lipolysis were observed, resulting in greater TG accumulation in the subcutaneous fat pad, with a shift in the ratio of TG between depots. These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR. 2010 Elsevier Inc. All rights reserved.

  1. Effects of Calorie Restriction in Obese Older Adults: The CROSSROADS Randomized Controlled Trial.

    PubMed

    Ard, Jamy D; Gower, Barbara; Hunter, Gary; Ritchie, Christine S; Roth, David L; Goss, Amy; Wingo, Brooks C; Bodner, Eric V; Brown, Cynthia J; Bryan, David; Buys, David R; Haas, Marilyn C; Keita, Akilah Dulin; Flagg, Lee Anne; Williams, Courtney P; Locher, Julie L

    2016-12-21

    We lack a comprehensive assessment of the risks and benefits of calorie restriction in older adults at high risk for cardiometabolic disease. Calorie restriction may reduce visceral adipose tissue (VAT) but also have negative effects on lean mass and quality of life. We conducted a 52-week, randomized controlled trial involving 164 older adults with obesity taking at least one medication for hyperlipidemia, hypertension, or diabetes. Interventions included an exercise intervention alone (Exercise), or with diet modification and body weight maintenance (Maintenance), or with diet modification and energy restriction (Weight Loss). The primary outcome was change in VAT at 12 months. Secondary outcomes included cardiometabolic risk factors, functional status, and quality of life. A total of 148 participants had measured weight at 12 months. Despite loss of -1.6% ± 0.3% body fat and 4.1% ± 0.7% initial body weight, Weight Loss did not have statistically greater loss of VAT (-192.6 ± 185.2 cm(3)) or lean mass (-0.4 ± 0.3 kg) compared with Exercise (VAT = -21.9 ± 173.7 cm(3); lean mass = 0.3 ± 0.3 kg). Quality of life improved in all groups with no differences between groups. No significant changes in physical function were observed. Weight Loss had significantly greater improvements in blood glucose (-8.3 ± 3.6 mg/dL, p < .05) and HDL-cholesterol (5.3 ± 1.9, p < .01) compared with Exercise. There were no group differences in the frequency of adverse events. While moderate calorie restriction did not significantly decrease VAT in older adults at high risk for cardiometabolic disease, it did reduce total body fat and cardiometabolic risk factors without significantly more adverse events and lean mass loss. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Effect of L-carnitine Supplementation on Nutritional Status and Physical Performance Under Calorie Restriction.

    PubMed

    Jain, Swati; Singh, Som Nath

    2015-04-01

    L-carnitine is popular as a potential ergogenic aid because of its role in the conversion of fat into energy. The present study was undertaken to investigate the effect of short term supplementation of L-carnitine on metabolic markers and physical efficiency tests under short term calorie restriction. Male albino rats were divided into four groups (n = 12 in each)-control, calorie restricted (CR for 5 days, 25 % of basal food intake), L-carnitine supplemented (CAR, given orally for 5 days at a dose of 100 mg/kg), CR with L-carnitine supplementation (CR + CAR). Food intake and body weight of the rats were measured along with biochemical variables like blood glucose, tissue glycogen, plasma and muscle protein and enzymatic activities of CPT-1 (carnitine palmitoyl transferase-1) and AMP kinase. Results demonstrated that L-carnitine caused marked increase in muscle glycogen, plasma protein, CPT-1 activity and swim time of rats (P < 0.05) on short term supplementation. In addition to the substantive effects caused by CR alone, L-carnitine under CR significantly affected muscle glycogen, plasma protein, CPT-1 activity and AMP kinase (P < 0.05). Short term CR along with L-carnitine also resulted in increased swim time of rats than control, CR and L-carnitine treated rats (P < 0.05). The present study was an attempt towards developing an approach for better adherence to dietary restriction regimen, with the use of L-carnitine.

  3. CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1.

    PubMed

    Rona, Germana; Herdeiro, Ricardo; Mathias, Cristiane Juliano; Torres, Fernando Araripe; Pereira, Marcos Dias; Eleutherio, Elis

    2015-06-01

    Studies using different organisms revealed that reducing calorie intake, without malnutrition, known as calorie restriction (CR), increases life span, but its mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to increase longevity, as well as to confer protection against lipid and protein oxidation under CR. Old cells of sod1 strain also presented a premature induction of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was overexpressed, sod1 and WT strains showed similar survival rates. Furthermore, CTT1 overexpression decreased lipid peroxidation and delayed the induction of apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a slower rate. However, the quantity of peroxide produced from superoxide in this way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital importance, because in the presence of a reducer transition metal peroxide is reduced to the highly reactive hydroxyl radical, which reacts indiscriminately with most cellular constituents. These findings might explain why overexpression of catalase was able to overcome the deficiency of Sod1p, increasing life span in response to CR.

  4. What are the roles of calorie restriction and diet quality in promoting healthy longevity?

    PubMed

    Rizza, Wanda; Veronese, Nicola; Fontana, Luigi

    2014-01-01

    Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets. More studies are needed to understand the interactions among single nutrient modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and minerals), the degree of CR and the frequency of food consumption in modulating anti-aging metabolic and molecular pathways, and in the prevention of age-associated diseases.

  5. Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives

    PubMed Central

    Marzetti, Emanuele; Wohlgemuth, Stephanie E.; Anton, Stephen D.; Bernabei, Roberto; Carter, Christy S.; Leeuwenburgh, Christiaan

    2009-01-01

    Synopsis Evidence from animal models and preliminary studies in humans indicate that calorie restriction (CR) delays cardiac aging and can prevent cardiovascular disease. These effects are mediated by a wide spectrum of biochemical and cellular adaptations, including redox homeostasis, mitochondrial function, inflammation, apoptosis and autophagy. Despite the beneficial effects of CR, its large-scale implementation is challenged by applicability issues as well as health concerns. However, preclinical studies indicate that specific compounds, such as resveratrol, may mimic many of the effects of CR, thus potentially obviating the need for drastic food intake reductions. Results from ongoing clinical trials will reveal whether the intriguing alternative of CR mimetics represents a safe and effective strategy to promote cardiovascular health and delay cardiac aging in humans. PMID:19944269

  6. The arcuate nucleus and NPY contribute to the antitumorigenic effect of calorie restriction

    PubMed Central

    Minor, Robin K.; López, Miguel; Younts, Caitlin M.; Jones, Bruce; Pearson, Kevin J.; Anson, R. Michael; Diéguez, Carlos; de Cabo, Rafael

    2011-01-01

    Summary Calorie restriction (CR) is known to have profound effects on tumor incidence. A typical consequence of CR is hunger, and we hypothesized that the neuroendocrine response to CR might in part mediate CR's antitumor effects. We tested CR under appetite suppression using two models: neuropeptide Y (NPY) knockout mice and monosodium glutamate (MSG)-injected mice. While CR was protective in control mice challenged with a two-stage skin carcinogenesis model, papilloma development was neither delayed nor reduced by CR in the MSG-treated and NPY knockout mice. Adiponectin levels were also not increased by CR in the appetite-suppressed mice. We propose that some of CR’s beneficial effects cannot be separated from those imposed on appetite, and that NPY neurons in the arcuate nucleus of the hypothalamus (ARC) are involved in the translation of reduced intake to downstream physiological and functional benefits. PMID:21385308

  7. Resolvin D1 primes the resolution process initiated by calorie restriction in obesity-induced steatohepatitis.

    PubMed

    Rius, Bibiana; Titos, Esther; Morán-Salvador, Eva; López-Vicario, Cristina; García-Alonso, Verónica; González-Périz, Ana; Arroyo, Vicente; Clària, Joan

    2014-02-01

    Insulin resistance and nonalcoholic steatohepatitis (NASH), characterized by hepatic steatosis combined with inflammation, are major sequelae of obesity. Currently, lifestyle modification (i.e., weight loss) is the first-line therapy for NASH. However, weight loss resolves steatosis but not inflammation. In this study, we tested the ability of resolvin D1 (RvD1), an anti-inflammatory and proresolving molecule, to promote the resolution initiated by calorie restriction in obese mice with NASH. Calorie restriction reduced adipose and liver weight (-56 and -13%, respectively; P<0.001), serum leptin and resistin levels, hepatic steatosis, and insulin resistance. In addition to these, mice receiving RvD1 during the dietary intervention showed increased adiponectin expression at both the mRNA and protein levels and reduced liver macrophage infiltration (-15%, P<0.01). Moreover, RvD1 skewed macrophages from an M1- to an M2-like anti-inflammatory phenotype, induced a specific hepatic miRNA signature (i.e., miR-219-5p and miR-199a-5p), and reduced inflammatory adipokine mRNA and protein expression and macrophage innate immune response. In precision-cut liver slices (PCLSs), which override the influence of circulating factors, RvD1 attenuated hypoxia-induced mRNA and protein expression of COX-2, IL-1β, IL-6, and CCR7. Of note, RvD1 anti-inflammatory actions were absent in macrophage-depleted PCLSs. In summary, RvD1 acts as a facilitator of the hepatic resolution process by reducing the inflammatory component of obesity-induced NASH.

  8. Inhibition of retinoic acid-induced skin irritation in calorie-restricted mice.

    PubMed

    Varani, James; Bhagavathula, Narasimharao; Aslam, Muhammad Nadeem; Fay, Kevin; Warner, Roscoe L; Hanosh, Andrew; Barron, Adam G; Miller, Richard A

    2008-01-01

    Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.

  9. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings.

    PubMed

    Barnosky, Adrienne R; Hoddy, Kristin K; Unterman, Terry G; Varady, Krista A

    2014-10-01

    Intermittent fasting (IF) regimens have gained considerable popularity in recent years, as some people find these diets easier to follow than traditional calorie restriction (CR) approaches. IF involves restricting energy intake on 1-3 d/wk, and eating freely on the nonrestriction days. Alternate day fasting (ADF) is a subclass of IF, which consists of a "fast day" (75% energy restriction) alternating with a "feed day" (ad libitum food consumption). Recent findings suggest that IF and ADF are equally as effective as CR for weight loss and cardioprotection. What remains unclear, however, is whether IF/ADF elicits comparable improvements in diabetes risk indicators, when compared with CR. Accordingly, the goal of this review was to compare the effects of IF and ADF with daily CR on body weight, fasting glucose, fasting insulin, and insulin sensitivity in overweight and obese adults. Results reveal superior decreases in body weight by CR vs IF/ADF regimens, yet comparable reductions in visceral fat mass, fasting insulin, and insulin resistance. None of the interventions produced clinically meaningful reductions in glucose concentrations. Taken together, these preliminary findings show promise for the use of IF and ADF as alternatives to CR for weight loss and type 2 diabetes risk reduction in overweight and obese populations, but more research is required before solid conclusions can be reached.

  10. Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts

    PubMed Central

    Galet, Colette; Gray, Ashley; Said, Jonathan W.; Castor, Brandon; Wan, Junxiang; Beltran, Pedro J.; Calzone, Franck J.; Elashoff, David; Cohen, Pinchas; Aronson, William J.

    2013-01-01

    Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile. PMID:23823800

  11. Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts.

    PubMed

    Galet, Colette; Gray, Ashley; Said, Jonathan W; Castor, Brandon; Wan, Junxiang; Beltran, Pedro J; Calzone, Franck J; Elashoff, David; Cohen, Pinchas; Aronson, William J

    2013-07-03

    Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.

  12. Approaches for quantifying energy intake and % calorie restriction (CR) during CR interventions in humans: the multicenter CALERIE study

    USDA-ARS?s Scientific Manuscript database

    Calorie restriction (CR) is a component of most weight-loss interventions and a potential strategy to slow aging. Accurate determination of energy intake and %CR is critical when interpreting the results of CR interventions; this is best achieved using the doubly labeled water method to quantify tot...

  13. Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

    PubMed Central

    Abraham, Karan J.; Chan, Janet N.Y.; Salvi, Jayesh S.; Ho, Brandon; Hall, Amanda; Vidya, Elva; Guo, Ru; Killackey, Samuel A.; Liu, Nancy; Lee, Jeffrey E.; Brown, Grant W.; Mekhail, Karim

    2016-01-01

    Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg2+) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg2+ is unknown. Here, we show that Mg2+, acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA–DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae, magnesium ions guided by cell membrane Mg2+ transporters Alr1/2 act via Mg2+-sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg2+ in a process that is dependent on the TRPM7 Mg2+ transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg2+ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes. PMID:27574117

  14. Acute effects of exercise and calorie restriction on triglyceride metabolism in women

    PubMed Central

    Bellou, Elena; Siopi, Aikaterina; Galani, Maria; Maraki, Maria; Tsekouras, Yiannis E.; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Magkos, Faidon; Sidossis, Labros S.

    2013-01-01

    The mechanisms by which exercise reduces fasting plasma triglyceride (TG) concentrations in women and the effect of negative energy balance independent of muscular contraction are not known. Purpose The aim of this study was to evaluate the effects of equivalent energy deficits induced by exercise or calorie restriction on basal very low-density lipoprotein (VLDL) TG metabolism in women. Methods Eleven healthy women (age: 23.5±2.7 years, BMI: 21.6±1.4 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) a single exercise bout (brisk walking at 60% of peak oxygen consumption for 123±18 min, with a net energy expenditure of 2.06±0.39 MJ (~500 kcal)), ii) dietary energy restriction of 2.10±0.41 MJ, and iii) a control day of isocaloric feeding and rest (zero energy balance). Results Fasting plasma VLDL-TG concentration was ~30% lower after the exercise trial compared to the control trial (P<0.001), whereas no significant change was detected after the calorie restriction trial (P=0.297 vs control). Relative to the control condition, exercise increased the plasma clearance rate of VLDL-TG by 22% (P=0.001) and reduced hepatic VLDL-TG secretion rate by ~17% (P=0.042), whereas hypocaloric diet had no effect on VLDL-TG kinetics (P>0.2). Conclusion (i) Exercise-induced hypotriglyceridemia in women manifests through a different mechanism (increased clearance and decreased secretion of VLDL-TG) than that previously described in men (increased clearance of VLDL-TG only), and (ii) exercise affects TG homeostasis by eliciting changes in VLDL-TG kinetics that cannot be reproduced by an equivalent diet-induced energy deficit, indicating that these changes are independent of the exercise-induced negative energy balance but instead are specific to muscular contraction. PMID:23073216

  15. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo

    PubMed Central

    Smith, Jesse J; Kenney, Renée Deehan; Gagne, David J; Frushour, Brian P; Ladd, William; Galonek, Heidi L; Israelian, Kristine; Song, Jeffrey; Razvadauskaite, Giedre; Lynch, Amy V; Carney, David P; Johnson, Robin J; Lavu, Siva; Iffland, Andre; Elliott, Peter J; Lambert, Philip D; Elliston, Keith O; Jirousek, Michael R; Milne, Jill C; Boss, Olivier

    2009-01-01

    Background Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetylase SIRT1 has been implicated as one of the key downstream regulators of CR in yeast, rodents, and humans. Small molecule activators of SIRT1 have been identified that exhibit efficacy in animal models of diseases typically associated with aging including type 2 diabetes. To identify molecular processes induced in the liver of mice treated with two structurally distinct SIRT1 activators, SIRT501 (formulated resveratrol) and SRT1720, for three days, we utilized a systems biology approach and applied Causal Network Modeling (CNM) on gene expression data to elucidate downstream effects of SIRT1 activation. Results Here we demonstrate that SIRT1 activators recapitulate many of the molecular events downstream of CR in vivo, such as enhancing mitochondrial biogenesis, improving metabolic signaling pathways, and blunting pro-inflammatory pathways in mice fed a high fat, high calorie diet. Conclusion CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials. PMID:19284563

  16. Calorie Restriction: What Recent Results Suggest for the Future of Aging Research

    PubMed Central

    Smith, Daniel L.; Nagy, Tim R.; Allison, David B.

    2010-01-01

    Background Calorie Restriction (CR) research has expanded rapidly over the past few decades and CR remains the most highly reproducible, environmental intervention to improve health and extend lifespan in animal studies. Although many model organisms have consistently demonstrated positive responses to CR, it remains to be shown whether CR will extend lifespan in humans. Additionally, the current environment of excess caloric consumption and high incidence of overweight/obesity illustrate the improbable nature of the long-term adoption of a CR lifestyle by a significant proportion of the human population. Thus, the search for substances that can reproduce the beneficial physiologic responses of CR without a requisite calorie intake reduction, termed CR mimetics (CRMs), has gained momentum. Material & Methods Recent articles describing health and lifespan results of CR in nonhuman primates and short-term human studies are discussed. Additional consideration is given to the rapidly expanding search for CRMs. Results The first results from a long-term, randomized, controlled CR study in nonhuman primates showing statistically significant benefits on longevity have now been reported. Additionally, positive results from short-term, randomized, controlled CR studies in humans are suggestive of potential health and longevity gains, while test of proposed CRMs (including rapamycin, resveratrol, 2-deoxyglucose and metformin) have shown both positive and mixed results in rodents. Conclusion Whether current positive results will translate into longevity gains for humans remains an open question. However, the apparent health benefits that have been observed with CR suggest that regardless of longevity gains, the promotion of healthy aging and disease prevention may be attainable. PMID:20534066

  17. Effects of mild calorie restriction on lipid metabolism and inflammation in liver and adipose tissue.

    PubMed

    Park, Chan Yoon; Park, Soyoung; Kim, Min Soo; Kim, Hye-Kyeong; Han, Sung Nim

    2017-08-26

    Calorie restriction (CR) has been reported to improve lipid metabolism and to decrease inflammatory diseases. However, most existing CR models use 30-50% calorie reduction, which is hard to achieve in humans. We investigated the effects of mild CR on lipid metabolism and inflammatory responses. Male C57BL/6 mice were fed control diet (10% kcal fat, Control) or high fat diet (60% kcal fat, HFD) ad libitum or reduced amount of control diet to achieve 15% CR for 16 wks. Body weights, white adipose tissue weights, liver triacylglycerol levels, and serum fetuin-A levels were lower in CR than in the Control. Serum adiponectin levels were higher in CR and lower in HFD compared with the Control. Liver and adipose tissue Mcp-1 mRNA levels were significantly lower in CR compared with the Control. Adipose tissue mRNA levels of Mcp-1, Il-6, Tnf-α and Socs3 were significantly higher in HFD than in the Control and CR, and levels of these negatively correlated with serum adiponectin levels. CR group had the lowest leptin levels and the highest liver Lepr expression, and Lepr mRNA levels positively correlated with liver Socs3 mRNA levels. Our findings showed that mild CR lowered adiposity which resulted in higher adiponectin and lower fetuin-A levels, and might have contributed to alleviation of inflammatory status in the liver and adipose tissue. Furthermore, mild CR might have affected leptin sensitivity by up-regulating Lepr expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Extended calorie restriction suppresses overall and specific food cravings: a systematic review and a meta-analysis.

    PubMed

    Kahathuduwa, C N; Binks, M; Martin, C K; Dawson, J A

    2017-10-01

    Multiple studies have concluded that calorie restriction for at least 12 weeks is associated with reduced food cravings, while others have shown that calorie restriction may increase food cravings. We addressed this ambiguity in a systematic review and meta-analysis. We searched for studies conducted on subjects with obesity, implemented calorie restriction for at least 12 weeks and measured food cravings pre-intervention and post-intervention. Our final eight studies mostly used the Food Craving Inventory. Other comparable methods were converted to a similar scale. We used the duration ≥12 weeks, but closest to 16 weeks for studies with multiple follow-ups and performed DerSimonian-Laird random-effects meta-analyses using the 'metafor' package in r software. Despite heterogeneity across studies, we observed reductions in pooled effects for overall food cravings (-0.246 [-0.490, -0.001]) as well as cravings for sweet (-0.410 [-0.626, -0.194]), high-fat (-0.190 [-0.343, -0.037]), starchy (-0.288 [-0.517, -0.058]) and fast food (-0.340 [-0.633, -0.048]) in the meta-analysis. Baseline body weight, type of intervention, duration, sample size and percentage of female subjects explained the heterogeneity. Calorie restriction is associated with reduced food cravings supporting a de-conditioning model of craving reductions. Our findings should ease the minds of clinicians concerned about increased cravings in patients undergoing calorie restriction interventions. © 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

  19. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    PubMed

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system. Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens. Therefore, we propose

  20. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model

    PubMed Central

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Introduction Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer’s oxidative phosphorylation system. Methods Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Results Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Conclusions Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting

  1. Systematic review and meta-analysis reveals acutely elevated plasma cortisol following fasting but not less severe calorie restriction.

    PubMed

    Nakamura, Yuko; Walker, Brian R; Ikuta, Toshikazu

    2016-01-01

    Elevated plasma cortisol has been reported following caloric restriction, and may contribute to adverse effects including stress-induced overeating, but results from published studies are inconsistent. To clarify the effects of caloric restriction on plasma cortisol, and to assess cortisol as an indicator of stress during caloric restriction, we conducted a systematic review and meta-analysis of published studies in which cortisol was measured following caloric restriction without other manipulations in humans. We further compared effects of fasting, very low calorie diet (VLCD), and other less intense low calorie diet (LCD), as well as the duration of caloric restriction by meta-regression. Overall, caloric restriction significantly increased serum cortisol level in 13 studies (357 total participants). Fasting showed a very strong effect in increasing serum cortisol, while VLCD and LCD did not show significant increases. The meta-regression analysis showed a negative association between the serum cortisol level and the duration of caloric restriction, indicating serum cortisol is increased in the initial period of caloric restriction but decreased to the baseline level after several weeks. These results suggest that severe caloric restriction causes activation of the hypothalamic-pituitary-adrenal axis, which may be transient, but results in elevated cortisol which could mediate effects of starvation on brain and metabolic function as well as ameliorate weight loss.

  2. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction.

    PubMed

    Fusco, Salvatore; Ripoli, Cristian; Podda, Maria Vittoria; Ranieri, Sofia Chiatamone; Leone, Lucia; Toietta, Gabriele; McBurney, Michael W; Schütz, Günther; Riccio, Antonella; Grassi, Claudio; Galeotti, Tommaso; Pani, Giovambattista

    2012-01-10

    Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD(+)-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes.

  3. Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

    PubMed

    Tahara, Erich B; Cunha, Fernanda M; Basso, Thiago O; Della Bianca, Bianca E; Gombert, Andreas K; Kowaltowski, Alicia J

    2013-01-01

    Calorie restriction (CR) is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative) metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0)) S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0) cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

  4. Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators

    PubMed Central

    Cai, Huan; Daimon, Caitlin M.; Cong, Wei-na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen

    2014-01-01

    Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste–related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste–related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR. PMID:24077597

  5. HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise.

    PubMed

    Park, Bong-Sup; Henning, Paul C; Grant, Samuel C; Lee, Won Jun; Lee, Sang-Rok; Arjmandi, Bahram H; Kim, Jeong-Su

    2013-12-01

    To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. © 2013.

  6. Serum from humans on long-term calorie restriction enhances stress resistance in cell culture

    PubMed Central

    Salvatore, Francesco; Crosby, Seth D.; Fontana, Luigi

    2013-01-01

    Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well. PMID:23912304

  7. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.

    PubMed

    Hebert, Alexander S; Dittenhafer-Reed, Kristin E; Yu, Wei; Bailey, Derek J; Selen, Ebru Selin; Boersma, Melissa D; Carson, Joshua J; Tonelli, Marco; Balloon, Allison J; Higbee, Alan J; Westphall, Michael S; Pagliarini, David J; Prolla, Tomas A; Assadi-Porter, Fariba; Roy, Sushmita; Denu, John M; Coon, Joshua J

    2013-01-10

    Calorie restriction (CR) extends life span in diverse species. Mitochondria play a key role in CR adaptation; however, the molecular details remain elusive. We developed and applied a quantitative mass spectrometry method to probe the liver mitochondrial acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3. Quantification of 3,285 acetylation sites-2,193 from mitochondrial proteins-rendered a comprehensive atlas of the acetyl-proteome and enabled global site-specific, relative acetyl occupancy measurements between all four experimental conditions. Bioinformatic and biochemical analyses provided additional support for the effects of specific acetylation on mitochondrial protein function. Our results (1) reveal widespread reprogramming of mitochondrial protein acetylation in response to CR and SIRT3, (2) identify three biochemically distinct classes of acetylation sites, and (3) provide evidence that SIRT3 is a prominent regulator in CR adaptation by coordinately deacetylating proteins involved in diverse pathways of metabolism and mitochondrial maintenance.

  8. Transcriptional response according to strength of calorie restriction in Saccharomyces cerevisiae.

    PubMed

    Lee, Yae-Lim; Lee, Cheol-Koo

    2008-09-30

    To characterize gene expression that is dependent on the strength of calorie restriction (CR), we obtained transcriptome at different levels of glucose, which is a major energy and carbon source for budding yeast. To faithfully mimic mammalian CR in yeast culture, we reconstituted and grew seeding yeast cells in fresh 2% YPD media before inoculating into 2%, 1%, 0.5% and 0.25% YPD media to reflect different CR strengths. We collected and characterized 160 genes that responded to CR strength based on the rigorous statistical analyses of multiple test corrected ANOVA (adjusted p0.7). Based on the individual gene studies and the GO Term Finder analysis of 160 genes, we found that CR dose-dependently and gradually increased mitochondrial function at the transcriptional level. Therefore, we suggest these 160 genes are markers that respond to CR strength and that might be useful in elucidating CR mechanisms, especially how stronger CR extends life span more.

  9. Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension.

    PubMed

    Molin, Mikael; Demir, Ayse Banu

    2014-01-01

    Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.

  10. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

    PubMed

    Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

    2017-03-28

    Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1(df/df) dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

  11. Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling

    PubMed Central

    Zhang, Nannan; Li, Zhongchi; Mu, Wei; Li, Liyuan; Liang, Yaru; Lu, Maoyang; Wang, Zhuoran; Qiu, Ying; Wang, Zhao

    2016-01-01

    ABSTRACT Calorie restriction (CR) extends lifespan from yeast to mammals. SIRT6 is a member of the sirtuin family of NAD+-dependent histone deacetylases, which is responsible for mediating the effects of CR. The transcription factor NF-κB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6. Here we describe the crucial role of SIRT6 in aging and inflammation. We show that CR had improved renal insufficiency and enhanced SIRT6 expression after 6-month treatment in aged mice. Culture cells in low glucose (LG) conditions also showed resistance to cell senescence and enhanced SIRT6 expression compared to normal glucose (NG) group, showing beneficial effects of the CR-mimic cultural conditions. Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-κB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-κB signaling. These findings confirm the key status of CR and disclose the critical role of SIRT6 on aging and inflammation. PMID:26940461

  12. Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction.

    PubMed

    Zhu, Min; Lee, Garrick D; Ding, Liusong; Hu, Jingping; Qiu, Guang; de Cabo, Rafa; Bernier, Michel; Ingram, Donald K; Zou, Sige

    2007-08-01

    Alterations in adipogenesis could have significant impact on several aging processes. We previously reported that calorie restriction (CR) in rats significantly increases the level of circulating adiponectin, a distinctive marker of differentiated adipocytes, leading to a concerted modulation in the expression of key transcription target genes and, as a result, to increased fatty acid oxidation and reduced deleterious lipid accumulation in other tissues. These findings led us to investigate further the effects of aging on adipocytes and to determine how CR modulates adipogenic signaling in vivo. CR for 2 and 25 months, significantly increased the expression of PPARgamma, C/EBPbeta and Cdk-4, and partially attenuated age-related decline in C/EBPalpha expression relative to rats fed ad libitum (AL). As a result, adiponectin was upregulated at both mRNA and protein levels, resulting in activation of target genes involved in fatty acid oxidation and fatty acid synthesis, and greater responsiveness of adipose tissue to insulin. Moreover, CR significantly decreased the ratio of C/EBPbeta isoforms LAP/LIP, suggesting the suppression of gene transcription associated with terminal differentiation while facilitating preadipocytes proliferation. Morphometric analysis revealed a greater number of small adipocytes in CR relative to AL feeding. Immunostaining confirmed that small adipocytes were more strongly positive for adiponectin than the large ones. Overall these results suggest that CR increased the expression of adipogenic factors, and maintained the differentiated state of adipocytes, which is critically important for adiponectin biosynthesis and insulin sensitivity.

  13. Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast

    PubMed Central

    Aris, John P.; Alvers, Ashley L.; Ferraiuolo, Roy A.; Fishwick, Laura K.; Hanvivatpong, Amanda; Hu, Doreen; Kirlew, Christine; Leonard, Michael T.; Losin, Kyle J.; Marraffini, Michelle; Seo, Arnold Y.; Swanberg, Veronica; Westcott, Jennifer L.; Wood, Michael S.; Leeuwenburgh, Christiaan; Dunn, William A.

    2013-01-01

    We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions. PMID:23337777

  14. Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice

    PubMed Central

    Kim, Mi-Jung; Hacker, Timothy A.; Vermulst, Marc; Weindruch, Richard; Prolla, Tomas A.

    2017-01-01

    Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation. PMID:28158260

  15. The Influence of Dietary Fat Source on Life Span in Calorie Restricted Mice.

    PubMed

    López-Domínguez, José A; Ramsey, Jon J; Tran, Dianna; Imai, Denise M; Koehne, Amanda; Laing, Steven T; Griffey, Stephen M; Kim, Kyoungmi; Taylor, Sandra L; Hagopian, Kevork; Villalba, José M; López-Lluch, Guillermo; Navas, Plácido; McDonald, Roger B

    2015-10-01

    Calorie restriction (CR) without malnutrition extends life span in several animal models. It has been proposed that a decrease in the amount of polyunsaturated fatty acids (PUFAs), and especially n-3 fatty acids, in membrane phospholipids may contribute to life span extension with CR. Phospholipid PUFAs are sensitive to dietary fatty acid composition, and thus, the purpose of this study was to determine the influence of dietary lipids on life span in CR mice. C57BL/6J mice were assigned to four groups (a 5% CR control group and three 40% CR groups) and fed diets with soybean oil (high in n-6 PUFAs), fish oil (high in n-3 PUFAs), or lard (high in saturated and monounsaturated fatty acids) as the primary lipid source. Life span was increased (p < .05) in all CR groups compared to the Control mice. Life span was also increased (p < .05) in the CR lard mice compared to animals consuming either the CR fish or soybean oil diets. These results indicate that dietary lipid composition can influence life span in mice on CR, and suggest that a diet containing a low proportion of PUFAs and high proportion of monounsaturated and saturated fats may maximize life span in animals maintained on CR.

  16. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet.

    PubMed

    Seyfried, B Thomas N; Kiebish, Michael; Marsh, Jeremy; Mukherjee, Purna

    2009-09-01

    Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect), malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (beta-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  17. Food reward in the obese and after weight loss induced by calorie restriction and bariatric surgery.

    PubMed

    Berthoud, Hans-Rudolf; Zheng, Huiyuan; Shin, Andrew C

    2012-08-01

    Increased availability of tasty, energy-dense foods has been blamed as a major factor in the alarmingly high prevalence of obesity, diabetes, and metabolic disease, even in young age. A heated debate has started as to whether some of these foods should be considered addictive, similar to drugs and alcohol. One of the main arguments for food addiction is the similarity of the neural mechanisms underlying reward generation by foods and drugs. Here, we will discuss how food intake can generate reward and how behavioral and neural reward functions are different in obese subjects. Because most studies simply compare lean and obese subjects, it is not clear whether predisposing differences in reward functions cause overeating and weight gain, or whether repeated exposure or secondary effects of the obese state alter reward functions. While studies in both rodents and humans demonstrate preexisting differences in reward functions in the obese, studies in rodent models using calorie restriction and gastric bypass surgery show that some differences are reversible by weight loss and are therefore secondary to the obese state. © 2012 New York Academy of Sciences.

  18. Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

    PubMed Central

    Sitzmann, Brandon D.; Urbanski, Henryk F.

    2008-01-01

    Although less dramatic than in females, male mammals experience decreasing reproductive function during aging. In primates, multiple facets of the hypothalamic-pituitary-gonadal axis show evidence of gradual age-related decline, including behavioral, neuroendocrine and endocrine alterations such as decreased testosterone levels, reduced circulating dehydroepiandrosterone sulfate (DHEAS) levels, increased numbers of sperm abnormalities, and a general decline in physiological responses. In this review we consider a range of age-related changes in males. These measures, including more subtle aging characteristics, are interesting additional indices for detecting the timing of age-related changes in behavioral, neuroendocrine, and endocrine responses. Evidence of potential effects of calorie restriction as an intervention in reproductive aging is also discussed. A discernable decline occurs in both metabolic and reproductive endocrine processes during male aging. This cascade of events includes neuroendocrine and behavioral changes; biomarkers such as circulating DHEAS also show clear age-related decline. The varied changes that occur during male aging are considered in the context of primate aging in general. PMID:19424865

  19. Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats

    PubMed Central

    Pósa, Anikó; Kupai, Krisztina; Szalai, Zita; Veszelka, Médea; Török, Szilvia; Varga, Csaba

    2015-01-01

    The estrogen deficiency after menopause leads to overweight or obesity, and physical exercise is one of the important modulators of this body weight gain. Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO). OVX and SO groups were randomized into new groups based on the voluntary physical activity (with or without running) and the type of diet for 12 weeks. Rats were fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR). The metabolic syndrome was assessed by measuring the body weight gain, the glucose sensitivity, and the levels of insulin, triglyceride, leptin, and aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT). The exercise training combined with the CR resulted in improvements in the glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels were significantly higher in OVX rats fed with HT but these high values were suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with HT caused a significant increase in leptin level. Our data provide evidence that CR combined with voluntary physical exercise can be a very effective strategy to prevent the development of a metabolic syndrome induced by high calorie diet. PMID:25874022

  20. Nutrition and Healthy Ageing: Calorie Restriction or Polyphenol-Rich “MediterrAsian” Diet?

    PubMed Central

    Rimbach, Gerald

    2013-01-01

    Diet plays an important role in mammalian health and the prevention of chronic diseases such as cardiovascular disease (CVD). Incidence of CVD is low in many parts of Asia (e.g., Japan) and the Mediterranean area (e.g., Italy, Spain, Greece, and Turkey). The Asian and the Mediterranean diets are rich in fruit and vegetables, thereby providing high amounts of plant bioactives including polyphenols, glucosinolates, and antioxidant vitamins. Furthermore, oily fish which is rich in omega-3 fatty acids is an important part of the Asian (e.g., Japanese) and also of the Mediterranean diets. There are specific plant bioactives which predominantly occur in the Mediterranean (e.g., resveratrol from red wine, hydroxytyrosol, and oleuropein from olive oil) and in the Asian diets (e.g., isoflavones from soybean and epigallocatechin gallate from green tea). Interestingly, when compared to calorie restriction which has been repeatedly shown to increase healthspan, these polyphenols activate similar molecular targets such as Sirt1. We suggest that a so-called “MediterrAsian” diet combining sirtuin-activating foods (= sirtfoods) of the Asian as well as Mediterranean diet may be a promising dietary strategy in preventing chronic diseases, thereby ensuring health and healthy ageing. Future (human) studies are needed which take the concept suggested here of the MediterrAsian diet into account. PMID:24069505

  1. Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA-DNA hybrids.

    PubMed

    Abraham, Karan J; Chan, Janet N Y; Salvi, Jayesh S; Ho, Brandon; Hall, Amanda; Vidya, Elva; Guo, Ru; Killackey, Samuel A; Liu, Nancy; Lee, Jeffrey E; Brown, Grant W; Mekhail, Karim

    2016-10-14

    Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg(2+)) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg(2+) is unknown. Here, we show that Mg(2+), acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA-DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae, magnesium ions guided by cell membrane Mg(2+) transporters Alr1/2 act via Mg(2+)-sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg(2+) in a process that is dependent on the TRPM7 Mg(2+) transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg(2+) as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Effects of Moderate Aerobic Exercise Combined With Calorie Restriction on Circulating Estrogens and IGF-I in Premenopausal Women

    DTIC Science & Technology

    2004-10-01

    Kines 496c Kines 496c Kines 596c Kines 597i Kines 395b Scientific basis of Exercise for Older Adults Independent Study 3 Fitness Appraisal 4...AD Award Number: DAMD17-01-1-0360 TITLE: Effects of Moderate Aerobic Exercise Combined with Calorie Restriction on Circulating Estrogens and IGF...AND DATES COVERED Annual Summary (17 Sep 2003 - 16 Sep 2004) 4. TITLE AND SUBTITLE Effects of Moderate Aerobic Exercise Combined with

  3. Appetite and gut peptide responses to exercise and calorie restriction. The effect of modest energy deficits.

    PubMed

    Deighton, Kevin; Batterham, Rachel L; Stensel, David J

    2014-10-01

    Weight loss is the result of a sustained negative energy balance, which is typically achieved by decreasing food intake and/or increasing physical activity. Current evidence suggests that acute energy deficits of ~4820 kJ elicit contrasting homeostatic responses when induced by exercise and food restriction but the response to government-recommended energy deficits is unknown. Twelve healthy men (mean(SD): age 24(5) years, body mass index 23.8(2.7) kg⋅m(-2), maximum oxygen uptake 55.4(9.1) mL⋅kg(-1)⋅min(-1)) completed three 8 h trials (control (Con), exercise-induced energy deficit (Ex-Def) and food restriction (Food-Def)) separated by 1 week. Thirty minutes of cycling at 64.5(3.2)% of maximum oxygen uptake was performed in Ex-Def from 0 to 0.5 h, which induced an energy deficit of 1469(256) kJ. An equivalent energy deficit was induced in Food-Def (1478(275) kJ) by reducing the energy content of standardised test meals at 1 h and 4 h. Appetite ratings, acylated ghrelin and peptide YY3-36 concentrations were measured throughout each trial. An ad libitum meal was provided at 7 h. Appetite was higher in Food-Def than Ex-Def from 4 to 8 h (P = 0.033) and tended to be higher across the entire 8 h trial (P = 0.059). However, energy intake at the ad libitum meal did not differ between trials (P = 0.634; Con 4376 (1634); Food-Def 4481 (1846); Ex-Def 4217 (1850) kJ). Acylated ghrelin was not related to changes in appetite but plasma PYY3-36 concentrations were higher in Ex-Def than Food-Def (P < 0.05) and negatively correlated with changes in appetite across the entire 8 h trial (P = 0.037). An energy deficit of ~1475 kJ stimulated compensatory increases in appetite when induced via calorie restriction but not when achieved by an acute bout of exercise. Appetite responses were associated with changes in plasma PYY3-36 but not acylated ghrelin concentrations and did not influence subsequent energy intake. Copyright

  4. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension.

    PubMed

    Wei, Min; Fabrizio, Paola; Madia, Federica; Hu, Jia; Ge, Huanying; Li, Lei M; Longo, Valter D

    2009-05-01

    The effect of calorie restriction (CR) on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K) is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Delta, tor1Delta, and ras2Delta mutants, was sufficient to reverse chronological life span extension in sch9Delta mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

  5. Regulation of Selenoproteins and Methionine Sulfoxide Reductases A and B1 by Age, Calorie Restriction, and Dietary Selenium in Mice

    PubMed Central

    Novoselov, Sergey V.; Kim, Hwa-Young; Hua, Deame; Lee, Byung Cheon; Astle, Clinton M.; Harrison, David E.; Friguet, Bertrand; Moustafa, Mohamed E.; Carlson, Bradley A.; Hatfield, Dolph L.

    2010-01-01

    Abstract Methionine residues are susceptible to oxidation, but this damage may be reversed by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the major methionine sulfoxide reductase in liver of mice and it is among the proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA activities, were reduced with age, and the selenium regulation of MsrB1 was preserved in the aging liver, suggesting that MsrB1 could account for the impaired methionine sulfoxide reduction in aging animals. We also examined regulation of Msr and selenoprotein expression by a combination of dietary selenium and calorie restriction and found that, under calorie restriction conditions, selenium regulation was preserved. In addition, mice overexpressing a mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed in selenium deficiency, whereas MsrA activity was elevated in these animals. Finally, we show that selenium regulation in inbred mouse strains is preserved in an outbred aging model. Taken together, these findings better define dietary regulation of methionine sulfoxide reduction and selenoprotein expression in mice with regard to age, calorie restriction, dietary Se, and a combination of these factors. Antioxid. Redox Signal. 12, 829–838. PMID:19769460

  6. The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

    PubMed Central

    Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L.; Chen, Luonan; Han, Jing-Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Douglas, Alex; Lusseau, David; Speakman, John R.

    2015-01-01

    A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30–35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect. PMID:26286956

  7. The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse.

    PubMed

    Mitchell, Sharon E; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Douglas, Alex; Lusseau, David; Speakman, John R

    2015-07-30

    A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30-35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect.

  8. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  9. Brain regions involved in ingestive behavior and related psychological constructs in people undergoing calorie restriction.

    PubMed

    Kahathuduwa, Chanaka N; Boyd, Lori A; Davis, Tyler; O'Boyle, Michael; Binks, Martin

    2016-12-01

    Human food intake is regulated by physiological energy homeostatic mechanisms and hedonic mechanisms. These are affected by both very short-term and longer-term calorie restriction (CR). To date, there are parallel discussions in the literature that fail to integrate across these disciplines and topics. First, much of the available neuroimaging research focusses on specific functional paradigms (e.g. reward, energy homeostasis). These paradigms often fail to consider more complex and inclusive models that examine how potential brain regions of interest interact to influence ingestion. Second, the paradigms used focus primarily on short-term CR (fasting) which has limited generalizability to clinical application. Finally, the behavioral literature, while frequently examining longer-term CR and related psychological constructs in the context of weight management (e.g. hedonic restraint, 'liking', 'wanting' and food craving), fails to adequately tie these phenomena to underlying neural mechanisms. The result is a less than complete picture of the brain's role in the complexity of the human experience of ingestion. This disconnect highlights a major limitation in the CR literature, where attempts are persistently made to exert behavioral control over ingestion, without fully understanding the complex bio behavioral systems involved. In this review we attempt to summarize all potential brain regions important for human ingestion, present a broad conceptual overview of the brain's multifaceted role in ingestive behavior, the human (psychological) experiences related to ingestion and to examine how these factors differ according to three forms of CR. These include short-term fasting, extended CR, and restrained eating. We aim to bring together the neuroimaging literature with the behavioral literature within a conceptual framework that may inform future translational research. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

    PubMed Central

    Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M. C; Zeeuw, Chris I. De; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

    2006-01-01

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPDG602D/R722W/XPA−/−) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80 −/− mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage. PMID:17173483

  11. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    SciTech Connect

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  12. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    PubMed

    van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M C; De Zeeuw, Chris I; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J; Mitchell, James R

    2006-12-15

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(-/-)) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/-) mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  13. Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria.

    PubMed

    Hagopian, Kevork; Harper, Mary-Ellen; Ram, Jesmon J; Humble, Stephen J; Weindruch, Richard; Ramsey, Jon J

    2005-04-01

    Calorie restriction (CR) without malnutrition increases maximal life span in diverse species. It has been proposed that reduction in energy expenditure and reactive oxygen species (ROS) production could be a mechanism for life span extension with CR. As a step toward testing this theory, mitochondrial proton leak, H2O2 production, and markers of oxidative stress were measured in liver from FBNF1 rats fed control or 40% CR diets for 12 or 18 mo. CR was initiated at 6 mo of age. Proton leak kinetics curves, generated from simultaneous measures of oxygen consumption and membrane potential, indicated a decrease in proton leak after 18 mo of CR, while only a trend toward a proton leak decrease was observed after 12 mo. Significant shifts in phosphorylation and substrate oxidation curves also occurred with CR; however, these changes occurred in concert with the proton leak changes. Metabolic control analysis indicated no difference in the overall pattern of control of the oxidative phosphorylation system between control and CR animals. At 12 mo, no significant differences were observed between groups for H2O2 production or markers of oxidative stress. However, at 18 mo, protein carbonyl content was lower in CR animals, as was H2O2 production when mitochondria were respiring on either succinate alone or pyruvate plus malate in the presence of rotenone. These results indicate that long-term CR lowers mitochondrial proton leak and H2O2 production, and this is consistent with the idea that CR may act by decreasing energy expenditure and ROS production.

  14. Metabolizable energy intake during long-term calorie restriction in rhesus monkeys.

    PubMed

    Raman, Aarthi; Baum, Scott T; Colman, Ricki J; Kemnitz, Joseph W; Weindruch, Richard; Schoeller, Dale A

    2007-10-01

    Calorie restriction (CR) is a dietary intervention shown to increase maximum life-span. The aim of this study was to compare the metabolizable energy of the pelleted semi-purified diet with estimated energy intake from food weight. Energy density of diet, urine and feces were measured by bomb calorimetry in rhesus monkeys (23-29 years old) on CR (CR, n=11) and control (C, n=9). Food moisture was measured to be 2-fold higher (9+/-1%) than indicated on the label (approximately 5%). The measured gross energy of diet was 4.4 kcal/g dry weight of CR and 4.5 kcal/g dry weight of C diets. In a two-day trial, food intake (mean+/-SD) was 112+/-20 g and 136+/-26 g of dry mass/d in the CR and C monkeys, respectively (p=0.003). The fraction of the diet absorbed (CR=0.91; C=0.95) was different (p<0.001) between CR and C monkeys. Using these coefficients, the metabolizable energy intake averaged over 6 months was 450+/-53 and 534+/-97 kcal/d in CR and C monkeys, respectively (Diff=16%; p=0.03). These values were compared with energy expenditure (EE), as measured annually by indirect calorimetry (490+/-61 kcal/d in CR and 532+/-62 kcal/d in C monkeys). Adjusted for changes in body composition (2+/-10 kcal/d in CR and -7+/-12 kcal/d in C), energy balance was not different from zero in CR (-42+/-42 kcal/d) and C (9+/-61 kcal/d) monkeys. Use of diet weight is a reasonable estimate of the level of CR when food waste is assessed.

  15. Effect of dietary modification by calorie restriction on cholesterol levels in lipoprotein(a) and other lipoprotein classes.

    PubMed

    Hirowatari, Yuji; Manita, Daisuke; Kamachi, Keiko; Tanaka, Akira

    2017-09-01

    Background Dietary habits are associated with obesity which is a risk factor for coronary heart disease. The objective is to estimate the change of lipoprotein(a) and other lipoprotein classes by calorie restriction with obesity index and Framingham risk score. Methods Sixty females (56 ± 9 years) were recruited. Their caloric intakes were reduced during the six-month period, and the calorie from fat was not more than 30%. Lipoprotein profiles were estimated at baseline and after the six-month period of calorie restriction. Cholesterol levels in six lipoprotein classes (HDL, LDL, IDL, VLDL, chylomicron and lipoprotein(a)) were analysed by anion-exchange liquid chromatography. The other tests were analysed by general methods. Additionally, Framingham risk score for predicting 10-year coronary heart disease risk was calculated. Results Body mass index, waist circumference, insulin resistance, Framingham risk score, total cholesterol, LDL-cholesterol and IDL-cholesterol were significantly decreased by the calorie restriction, and the protein and cholesterol levels of lipoprotein(a) were significantly increased. The change of body mass index was significantly correlated with those of TC, VLDL-cholesterol and chylomicron-cholesterol, and that of waist circumference was significantly correlated with that of chylomicron-cholesterol. The change of Framingham risk score was significantly correlated with the change of IDL-C. Conclusion Obesity indexes and Framingham risk score were reduced by the dietary modification. Lipoprotein profile was improved with the reduction of obesity indexes, but lipoprotein(a) was increased. The changes of obesity indexes and Framingham risk score were related with those of triglyceride-rich lipoproteins, e.g. IDL, VLDL and CM.

  16. Growth hormone abolishes beneficial effects of calorie restriction in long-lived Ames dwarf mice.

    PubMed

    Gesing, Adam; Al-Regaiey, Khalid A; Bartke, Andrzej; Masternak, Michal M

    2014-10-01

    Disruption of the growth hormone (GH) axis promotes longevity and delays aging. In contrast, GH over-expression may lead to accelerated aging and shorter life. Calorie restriction (CR) improves insulin sensitivity and may extend lifespan. Long-lived Ames dwarf (df/df) mice have additional extension of longevity when subjected to 30% CR. The aim of the study was to assess effects of CR or GH replacement therapy separately and as a combined (CR+GH) treatment in GH-deficient df/df and normal mice, on selected metabolic parameters (e.g., insulin, glucose, cholesterol), insulin signaling components (e.g., insulin receptor [IR] β-subunit, phosphorylated form of IR [IR pY1158], protein kinase C ζ/λ [p-PKCζ/λ] and mTOR [p-mTOR]), transcription factor p-CREB, and components of the mitogen-activated protein kinase (MAPK) signaling (p-ERK1/2, p-p38), responsible for cell proliferation, differentiation and survival. CR decreased plasma levels of insulin, glucose, cholesterol and leptin, and increased hepatic IR β-subunit and IR pY1158 levels as well as IR, IRS-1 and GLUT-2 gene expression compared to ad libitum feeding, showing a significant beneficial diet intervention effect. Moreover, hepatic protein levels of p-PKCζ/λ, p-mTOR and p-p38 decreased, and p-CREB increased in CR mice. On the contrary, GH increased levels of glucose, cholesterol and leptin in plasma, and p-mTOR or p-p38 in livers, and decreased plasma adiponectin and hepatic IR β-subunit compared to saline treatment. There were no GH effects on adiponectin in N mice. Moreover, GH replacement therapy did not affect IR, IRS-1 and GLUT-2 gene expression. GH treatment abolishes the beneficial effects of CR; it may suggest an important role of GH-IGF1 axis in mediating the CR action. Suppressed somatotrophic signaling seems to predominate over GH replacement therapy in the context of the examined parameters and signaling pathways.

  17. Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress.

    PubMed

    Rippe, Catarina; Lesniewski, Lisa; Connell, Melanie; LaRocca, Thomas; Donato, Anthony; Seals, Douglas

    2010-06-01

    To determine if short-term calorie restriction reverses vascular endothelial dysfunction in old mice, old (O, n = 30) and young (Y, n = 10) male B6D2F1 mice were fed ad libitum (AL) or calorie restricted (CR, approximately 30%) for 8 weeks. Ex vivo carotid artery endothelium-dependent dilation (EDD) was impaired in old ad libitum (OAL) vs. young ad libitum (YAL) (74 +/- 5 vs. 95 +/- 2% of maximum dilation, P < 0.05), whereas old calorie-restricted (OCR) and YCR did not differ (96 +/- 1 vs. 94 +/- 3%). Impaired EDD in OAL was mediated by reduced nitric oxide (NO) bioavailability associated with decreased endothelial NO synthase expression (aorta) (P < 0.05), both of which were restored in OCR. Nitrotyrosine, a cellular marker of oxidant modification, was markedly elevated in OAL (P < 0.05), whereas OCR was similar to Y. Aortic superoxide production was 150% greater in OAL vs. YAL (P < 0.05), but normalized in OCR, and TEMPOL, a superoxide dismutase (SOD) mimetic that restored EDD in OAL (to 97 +/- 2%), had no effect in Y or OCR. OAL had increased expression and activity of the oxidant enzyme, NADPH oxidase, and its inhibition (apocynin) improved EDD, whereas NADPH oxidase in OCR was similar to Y. Manganese SOD activity and sirtuin1 expression were reduced in OAL (P < 0.05), but restored to Y in OCR. Inflammatory cytokines were greater in OAL vs. YAL (P < 0.05), but unaffected by CR. Carotid artery endothelium-independent dilation did not differ among groups. Short-term CR initiated in old age reverses age-associated vascular endothelial dysfunction by restoring NO bioavailability, reducing oxidative stress (via reduced NADPH oxidase-mediated superoxide production and stimulation of anti-oxidant enzyme activity), and upregulation of sirtuin-1.

  18. Moderate calorie restriction during gestation programs offspring for lower BAT thermogenic capacity driven by thyroid and sympathetic signaling.

    PubMed

    Palou, M; Priego, T; Romero, M; Szostaczuk, N; Konieczna, J; Cabrer, C; Remesar, X; Palou, A; Pico, C

    2015-02-01

    Maternal calorie restriction during pregnancy programs offspring for later overweight and metabolic disturbances. Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and has recently emerged as a very likely target for human obesity therapy. Here we aimed to assess whether the detrimental effects of undernutrition during gestation could be related to impaired thermogenic capacity in BAT and to investigate the potential mechanisms involved. Offspring of control and 20% calorie-restricted rats (days 1-12 of pregnancy) (CR) were studied at the age of 25 days. Protein levels of uncoupling protein 1 (UCP1) and tyrosine hydroxylase (TyrOH); mRNA levels of lipoprotein lipase (LPL), carnitine palmitoyltransferase 1 (CPT1) and deiodinase iodothyronine type II (DIO2) in BAT; and blood parameters including thyroid hormones, were determined. The response to 24-h cold exposure was also studied by measuring body temperature changes over time, and final BAT UCP1 levels. Compared with controls, CR animals displayed in BAT lower UCP1 and TyrOH protein levels and lower LPL and CPT1 mRNA levels; they also showed lower triiodothyronine (T3) plasma levels. CR males, but not females, revealed lower DIO2 mRNA levels than controls. When exposed to cold, CR rats experienced a transient decline in body temperature, but the values were reestablished after 24 h, despite having lower UCP1 levels than controls. These results suggest that BAT thermogenic capacity is diminished in CR animals, involving impaired BAT sympathetic innervation and thyroid hormone signaling. These alterations make animals more sensitive to cold and may contribute to long-term outcomes of gestational calorie restriction in promoting obesity and related metabolic alterations.

  19. Podocyte hypertrophy, "adaptation," and "decompensation" associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restriction.

    PubMed

    Wiggins, Jocelyn E; Goyal, Meera; Sanden, Silja K; Wharram, Bryan L; Shedden, Kerby A; Misek, David E; Kuick, Rork D; Wiggins, Roger C

    2005-10-01

    Whether podocyte depletion could cause the glomerulosclerosis of aging in Fischer 344 rats at ages 2, 6, 17, and 24 mo was evaluated. Ad libitum-fed rats developed proteinuria and glomerulosclerosis by 24 mo, whereas calorie-restricted rats did not. No evidence of age-associated progressive linear loss of podocytes from glomeruli was found. Rather, ad libitum-fed rats developed glomerular enlargement over time. To accommodate the increased glomerular volume, podocytes principally underwent hypertrophy, whereas other glomerular cells underwent hyperplasia. Stages of hypertrophy through which podocytes pass en route to podocyte loss and glomerulosclerosis were identified: Stage 1, normal podocyte; stage 2, nonstressed podocyte hypertrophy; stage 3, "adaptive" podocyte hypertrophy manifest by changes in synthesis of structural components (e.g., desmin) but maintenance of normal function; stage 4, "decompensated" podocyte hypertrophy relative to total glomerular volume manifest by reduced production of key machinery necessary for normal podocyte function (e.g., Wilms' tumor 1 protein [WT1], transcription factor pod1, nephrin, glomerular epithelial protein 1, podocalyxin, vascular endothelial growth factor, and alpha5 type IV collagen) and associated with widened foot processes and decreased filter efficiency (proteinuria); and stage 5, podocyte numbers decrease in association with focal segmental glomerulosclerosis. In contrast, in calorie-restricted rats, glomerular enlargement was minor, significant podocyte hypertrophy did not occur, podocyte machinery was unchanged, there was no proteinuria, and glomerulosclerosis did not develop. Glomerular enlargement therefore was associated with podocyte hypertrophy rather than hyperplasia. Hypertrophy above a certain threshold was associated with podocyte stress and then failure, culminating in reduced podocyte numbers in sclerotic glomeruli. This process could be prevented by calorie restriction.

  20. Biological approaches to mechanistically understand the healthy life span extension achieved by calorie restriction and modulation of hormones.

    PubMed

    Barzilai, Nir; Bartke, Andrzej

    2009-02-01

    Calorie restriction and reduced somatotropic (growth hormone and insulin-like growth factor-1) signaling have a widespread though not universal ability to extend life. These interventions are considered central tools to understanding the downstream events that lead to the increase in healthy life span. As these approaches have been validated, the animals phenotyped, and the mechanisms proposed, many challenges have emerged. In this article, we give several examples and propose several considerations, opportunities, and approaches that may identify major mechanisms through which these interventions exert their effects, and which may lead to drug therapy to increase "health span."

  1. The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial.

    PubMed

    Schübel, Ruth; Graf, Mirja E; Nattenmüller, Johanna; Nabers, Diana; Sookthai, Disorn; Gruner, Laura F; Johnson, Theron; Schlett, Christopher L; von Stackelberg, Oyunbileg; Kirsten, Romy; Habermann, Nina; Kratz, Mario; Kauczor, Hans-Ulrich; Ulrich, Cornelia M; Kaaks, Rudolf; Kühn, Tilman

    2016-11-01

    Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans.

    PubMed

    Timmers, Silvie; Konings, Ellen; Bilet, Lena; Houtkooper, Riekelt H; van de Weijer, Tineke; Goossens, Gijs H; Hoeks, Joris; van der Krieken, Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Hesselink, Matthijs K C; Kunz, Iris; Schrauwen-Hinderling, Vera B; Blaak, Ellen; Auwerx, Johan; Schrauwen, Patrick

    2011-11-02

    Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Calorie restricted diet induces alternative pathways of lipid metabolism for support of proliferative processes in regenerating liver.

    PubMed

    Bozhkov, A I; Menzianova, N C

    2009-01-01

    This study deals with quality and quantity lipid composition of blood serum and liver, DNA synthesis activity (incorporation of H3-thymidine) in liver in 24 h after partial hepatectomy (PH) in 22-month-old Wistar rats, maintained for 21 months on calorie restricted diet (CRD) and on standard diet ad libitum (SD). The contain of lipids in blood serum and activity of RA-label incorporation (14C-Na-acetate) in serum lipids in 24 h after PH were the same in CRD-fed and SD-fed animals. Quantitative and qualitative composition of lipids in microsomes of regenerating liver also was the same for both groups of rats. In regenerating liver of CRD-fed animals lipid contain in cytosol was 1,8-fold more, but pool of lipid droplets (LD) was 1.5-fold less than in regenerating liver of SD-fed animals. Activity of RA-label incorporation in lipids of microsomes, cytosol and LD pool of regenerating liver of CRD-fed animals was significantly higher, than in SD-fed ones. Activity of RA-label incorporation in lipid fractions and its distribution among cytosol lipids and LD pool lipids differed significantly between SD- and CRD-fed animals. Activity of DNA synthesis in regenerating liver of 22-month-old animals on CRD and SD was the same. It is supposed that calorie restriction induces alternative pathways of lipid metabolism to support proliferation processes in liver after PH.

  4. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

    PubMed

    Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

    2009-06-19

    NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

  5. Lifestyle Intervention Involving Calorie Restriction with or without Aerobic Exercise Training Improves Liver Fat in Adults with Visceral Adiposity

    PubMed Central

    Kumahara, Hideaki; Matsuda, Takuro; Ayabe, Makoto; Anzai, Keizo; Higaki, Yasuki; Tanaka, Hiroaki

    2014-01-01

    Objective. To evaluate the effect of calorie restriction-induced weight loss with or without aerobic exercise on liver fat. Methods. Thirty-three adults with visceral adiposity were divided into calorie restriction (CR; n = 18) or CR and aerobic exercise (CR + Ex; n = 15) groups. Target energy intake was 25 kcal/kg of ideal body weight. The CR + Ex group had a targeted exercise time of 300 min/wk or more at lactate threshold intensity for 12 weeks. Results. Reductions in body weight (CR, −5.3 ± 0.8 kg; CR + Ex, −5.1 ± 0.7 kg), fat mass (CR, −4.9 ± 0.9 kg; CR + Ex, −4.4 ± 0.6 kg), and visceral fat (CR, −24 ± 5 cm2; CR + Ex, −37 ± 5 cm2) were not statistically different between groups. Liver fat decreased significantly in both groups, with no difference between groups. Change in maximal oxygen uptake was significantly greater in the CR + Ex group than in the CR group (CR, −0.7 ± 0.7 mL/kg/min; CR + Ex, 2.9 ± 1.0 mL/kg/min). Conclusion. Both CR and CR + Ex resulted in an improved reduction in liver fat; however, there was no additive effect of exercise training. PMID:24864199

  6. Differential sympathetic outflow to adipose depots is required for visceral fat loss in response to calorie restriction

    PubMed Central

    Sipe, L M; Yang, C; Ephrem, J; Garren, E; Hirsh, J; Deppmann, C D

    2017-01-01

    The sympathetic nervous system (SNS) regulates energy homeostasis in part by governing fatty acid liberation from adipose tissue. We first examined whether SNS activity toward discrete adipose depots changes in response to a weight loss diet in mice. We found that SNS activity toward each adipose depot is unique in timing, pattern of activation, and habituation with the most dramatic contrast between visceral and subcutaneous adipose depots. Sympathetic drive toward visceral epididymal adipose is more than doubled early in weight loss and then suppressed later in the diet when weight loss plateaued. Coincident with the decline in SNS activity toward visceral adipose is an increase in activity toward subcutaneous depots indicating a switch in lipolytic sources. In response to calorie restriction, SNS activity toward retroperitoneal and brown adipose depots is unaffected. Finally, pharmacological blockage of sympathetic activity on adipose tissue using the β3-adrenergic receptor antagonist, SR59230a, suppressed loss of visceral adipose mass in response to diet. These findings indicate that SNS activity toward discrete adipose depots is dynamic and potentially hierarchical. This pattern of sympathetic activation is required for energy liberation and loss of adipose tissue in response to calorie-restricted diet. PMID:28394360

  7. A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan

    PubMed Central

    Kwan, Elizabeth X.; Foss, Eric J.; Tsuchiyama, Scott; Alvino, Gina M.; Kruglyak, Leonid; Kaeberlein, Matt; Raghuraman, M. K.; Brewer, Bonita J.; Kennedy, Brian K.; Bedalov, Antonio

    2013-01-01

    Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics. PMID:23505383

  8. Effect of Intermittent versus Chronic Calorie Restriction on Tumor Incidence: A Systematic Review and Meta-Analysis of Animal Studies

    PubMed Central

    Chen, Yalan; Ling, Lifeng; Su, Guanglei; Han, Ming; Fan, Xikang; Xun, Pengcheng; Xu, Guangfei

    2016-01-01

    Both chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) have shown anticancer effects. However, the direct evidence comparing ICR to CCR with respect to cancer prevention is controversial and inconclusive. PubMed and Web of Science were searched on November 25, 2015. The relative risk (RR) [95% confidence interval (CI)] was calculated for tumor incidence, and the standardised mean difference (95% CI) was computed for levels of serum insulin-like growth factor-1 (IGF-1), leptin, and adiponectin using a random-effects meta-analysis. Sixteen studies were identified, including 11 using genetically engineered mouse models (908 animals with 38–76 weeks of follow-up) and 5 using chemically induced rat models (379 animals with 7–18 weeks of follow-up). Compared to CCR, ICR decreased tumor incidence in genetically engineered models (RR = 0.57; 95% CI: 0.37, 0.88) but increased the risk in chemically induced models (RR = 1.53, 95% CI: 1.13, 2.06). It appears that ICR decreases IGF-1 and leptin and increases adiponectin in genetically engineered models. Thus, the evidence suggests that ICR exerts greater anticancer effect in genetically engineered mouse models but weaker cancer prevention benefit in chemically induced rat models as compared to CCR. Further studies are warranted to confirm our findings and elucidate the mechanisms responsible for these effects. PMID:27653140

  9. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

    PubMed Central

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K. N.; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S. Sendhil

    2016-01-01

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

  10. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats.

    PubMed

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K N; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S Sendhil

    2016-05-20

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity.

  11. Neuropeptide Y resists excess loss of fat by lipolysis in calorie-restricted mice: a trait potential for the life-extending effect of calorie restriction.

    PubMed

    Park, Seongjoon; Komatsu, Toshimitsu; Kim, Sang Eun; Tanaka, Katsuya; Hayashi, Hiroko; Mori, Ryoichi; Shimokawa, Isao

    2017-04-01

    Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with lipodystrophy. NPY(-/-) mice displayed a rapid decrease in body weight and fat mass, as well as increased lipolysis during CR. These alterations in fat regulation were inhibited by the lipolysis inhibitor, acipimox, a treatment associated with reduced mortality. The lipolytic/thermogenic signaling, β3-adrenergic receptor/hormone sensitive lipase, was markedly activated in white adipose tissue of NPY(-/-) mice compared with that of NPY(+/+) mice, and thermogenesis was controlled by NPY under negative energy balance. These results demonstrate the critical role of NPY in the regulation of lipid metabolic homeostasis and survival via control of lipolysis and thermogenesis in a state of negative energy balance. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding.

    PubMed

    Rogozina, Olga P; Nkhata, Katai J; Nagle, Emily J; Grande, Joseph P; Cleary, Margot P

    2013-04-01

    Previously we reported that intermittent calorie restriction (ICR) provided greater prevention of mammary tumors (MTs) than chronic calorie restriction (CCR). Here the impact of increased fat intake during refeeding in an ICR protocol was evaluated. MMTV-TGF-α female mice were assigned to one of three groups: ad libitum (AL) fed (n = 45) with free access to a moderately high fat diet (22 % fat calories); ICR (n = 45) 50 % calorie restricted for 3-week intervals followed by 3 weeks of 100 % of AL intake; and CCR (n = 45) fed 75 % of AL mice, matching each 6-week cycle of ICR mice. ICR mice were further designated as ICR-Restricted or ICR-Refed for data obtained during these intervals. All mice consumed the same absolute amount of dietary fat. Mice were followed to assess MT incidence, body weight and serum IGF-1, IGFBP3, leptin and adiponectin levels until 79 (end of final 3-week restriction) or 82 (end of final 3-weeks refeeding) weeks of age. Age of MT detection was significantly extended for CCR (74 weeks) and ICR (82 weeks) mice, compared to 57.5 weeks for AL mice. MT incidence for AL, ICR and CCR mice was 66.7, 4.4, and 52.3 %, respectively. Mammary and fat pad weights were reduced significantly following 50 % calorie restriction in ICR-Restricted mice compared to AL, CCR and ICR-Refed mice. IGF-1 and leptin levels also tended to be reduced in ICR-Restricted mice over the course of the study while adiponectin was not compared to AL, CCR, and ICR-Refed mice. The adiponectin:leptin ratio was consistently higher following 50 % restriction in ICR-Restricted mice. There was no relationship of IGF-1, leptin, or adiponectin with the presence of MTs in any groups. Thus the manner in which calories are restricted impacts the protective effect of calorie restriction independently of high fat intake.

  13. Protein and Calorie Restriction Contribute Additively to Protection from Renal Ischemia Reperfusion Injury Partly via Leptin Reduction in Male Mice.

    PubMed

    Robertson, Lauren T; Treviño-Villarreal, J Humberto; Mejia, Pedro; Grondin, Yohann; Harputlugil, Eylul; Hine, Christopher; Vargas, Dorathy; Zheng, Hanqiao; Ozaki, C Keith; Kristal, Bruce S; Simpson, Stephen J; Mitchell, James R

    2015-08-01

    Short-term dietary restriction (DR) without malnutrition preconditions against surgical stress in rodents; however, the nutritional basis and underlying nutrient/energy-sensing pathways remain poorly understood. We investigated the relative contribution of protein restriction (PR) vs. calorie restriction (CR) to protection from renal ischemia reperfusion injury (IRI) and changes in organ-autonomous nutrient/energy-sensing pathways and hormones underlying beneficial effects. Mice were preconditioned on experimental diets lacking total calories (0-50% CR) or protein/essential amino acids (EAAs) vs. complete diets consumed ad libitum (AL) for 1 wk before IRI. Renal outcome was assessed by serum markers and histology and integrated over a 2-dimensional protein/energy landscape by geometric framework analysis. Changes in renal nutrient/energy-sensing signal transduction and systemic hormones leptin and adiponectin were also measured. The genetic requirement for amino acid sensing via general control non-derepressible 2 (GCN2) was tested with knockout vs. control mice. The involvement of the hormone leptin was tested by injection of recombinant protein vs. vehicle during the preconditioning period. CR-mediated protection was dose dependent up to 50% with maximal 2-fold effect sizes. PR benefits were abrogated by EAA re-addition and additive with CR, with maximal benefits at any given amount of CR occurring with a protein-free diet. GCN2 was not required for functional benefits of PR. Activation and repression of nutrient/energy-sensing kinases, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1), respectively, on PR reflected a state of negative energy balance, paralleled by 13% weight loss and an 87% decrease in leptin, independent of calorie intake. Recombinant leptin administration partially abrogated benefits of dietary preconditioning against renal IRI. In male mice, PR and CR both contributed to the benefits of short-term DR

  14. Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction

    PubMed Central

    Park, Seongjoon; Mori, Ryoichi; Shimokawa, Isao

    2013-01-01

    Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms underlying the longevity effect of CR. PMID:23661364

  15. Alterations of Ultrastructural and Fission/Fusion Markers in Hepatocyte Mitochondria From Mice Following Calorie Restriction With Different Dietary Fats

    PubMed Central

    2013-01-01

    We analyzed ultrastructural changes and markers of fission/fusion in hepatocyte mitochondria from mice submitted to 40% calorie restriction (CR) for 6 months versus ad-libitum-fed controls. To study the effects of dietary fat under CR, animals were separated into three CR groups with soybean oil (also in controls), fish oil, and lard. CR induced differential changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. The number of cristae per mitochondrion was significantly higher in all CR groups compared with controls. Proteins related to mitochondrial fission (Fis1 and Drp1) increased with CR, but no changes were detected in proteins involved in mitochondrial fusion (Mfn1, Mfn2, and OPA1). Although many of these changes could be attributed to CR regardless of dietary fat, changing membrane lipid composition by different fat sources did modulate the effects of CR on hepatocyte mitochondria. PMID:23403066

  16. Improvement in metabolic parameters in obese subjects after 16 weeks on a Brazilian-staple calorie-restricted diet

    PubMed Central

    Reis, Caio E. G.; da Silva, Fábio V. P.; Casulari, Luiz A.

    2014-01-01

    BACKGROUND/OBJECTIVES The standard pattern of Brazilian food consumption is based on the combination of rice and beans served together in the main meals. This study assessed the effects of Brazilian-staple calorie-restricted (BS-diet) dietary advice, with brown rice and beans, on metabolic parameters, body composition, and food intake in overweight/obese subjects. SUBJECTS/METHODS Twentyseven subjects were randomly assigned to a conventional-type calorie-restricted diet (CT-diet) (n = 13) or a BS-diet (n = 14). Glucose metabolism, lipid profile, anthropometric and body composition parameters, and food intake were measured before and after 16 weeks. Paired t-tests/Wilcoxon tests were used for comparison of differences from baseline and unpaired t-tests/Mann-Whitney tests were used for comparison of differences between the groups. RESULTS After 16 weeks, both groups showed reductions in weight and waist circumference (P < 0.02), and the BS-diet group showed a decrease in body fat (P = 0.0001), and significant improvement in glucose metabolism (fasting plasma glucose, glucose and insulin areas under the curve, Cederholm index, and HOMA2-%β) (P ≤ 0.04) and lipid profile (cholesterol, triacylglycerol, LDL-c, VLDL-c, and cholesterol/HDL-c ratio) (P ≤ 0.05). In addition, the BS-diet group showed significant improvement in HOMA2-%β, compared to the CT-diet group (P = 0.03). The BS-diet group also showed a significant reduction in energy, lipids, carbohydrate, and cholesterol intake (P ≤ 0.04) and an increase in fiber intake (P ≤ 0.001), while the CT-diet group showed a significant reduction in intake of energy, macronutrients, PUFA, and cholesterol (P ≤ 0.002). CONCLUSIONS These results demonstrate the benefits of the BS-diet on metabolic parameters in obese subjects. PMID:25110561

  17. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

    PubMed

    Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

    2016-04-01

    Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

  18. Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

    PubMed Central

    Srinivasan, Malathi; Mahmood, Saleh

    2013-01-01

    Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats. PMID:23249696

  19. Calorie-restricted ketogenic diet increases thresholds to all patterns of pentylenetetrazol-induced seizures: critical importance of electroclinical assessment.

    PubMed

    Raffo, Emmanuel; François, Jennifer; Ferrandon, Arielle; Koning, Estelle; Nehlig, Astrid

    2008-02-01

    Thresholds to pentylenetetrazol (PTZ) seizures were usually based only on clinical symptoms. Our purpose was to use electroclinical patterns to assess the efficacy of a ketogenic and/or calorie-restricted diet on PTZ-induced seizures. Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), and hypocalorie ketogenic (HK). After 21 days, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ. The clinical and EEG thresholds to each seizure pattern were compared between the different groups. The electroclinical course of PTZ-induced seizures was similar in all groups. The HK group exhibited higher thresholds than the other ones for most clinical features: absence (p = 0.003), first overt myoclonia (p = 0.028), clonic seizure (p = 0.006), and for EEG features: first spike (p = 0.036), first spike-and-wave discharge (p = 0.014), subcontinuous spike-and-wave discharges (p = 0.005). NK, HC, and NC groups were not significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. After the clonic seizure, despite stopping PTZ infusion, a tonic seizure occurred in some animals, without significant difference regarding the diet. This approach permitted a precise study of the electroclinical course of PTZ-induced seizures. In addition to the usually studied first overt myoclonia, we clearly demonstrated the efficiency of a calorie restricted KD in elevating thresholds to most electroclinical seizure patterns. We confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started.

  20. Short-term Calorie Restriction Reverses Vascular Endothelial Dysfunction in Old Mice by Increasing Nitric Oxide and Reducing Oxidative Stress

    PubMed Central

    Rippe, Catarina; Lesniewski, Lisa; Connell, Melanie; LaRocca, Thomas; Donato, Anthony; Seals, Douglas

    2010-01-01

    Summary To determine if short-term calorie restriction reverses vascular endothelial dysfunction in old mice, old (O, n=30) and young (Y, n=10) male B6D2F1 mice were fed ad libitum (AL) or calorie restricted (CR, ∼30%) for 8 weeks. Ex vivo carotid artery endothelium-dependent dilation (EDD) was impaired in OAL vs. YAL (74±5 vs. 95±2% of maximum dilation, P<0.05), whereas OCR and YCR did not differ (96±1 vs. 94±3%). Impaired EDD in OAL was mediated by reduced nitric oxide (NO) bioavailability associated with decreased endothelial NO synthase expression (aorta) (P<0.05), both of which were restored in OCR. Nitrotyrosine, a cellular marker of oxidant modification, was markedly elevated in OAL (P<0.05), whereas OCR was similar to Y. Aortic superoxide production was 150% greater in OAL vs. YAL (P<0.05), but normalized in OCR, and TEMPOL, a superoxide dismutase (SOD) mimetic that restored EDD in OAL (to 97±2%), had no effect in Y or OCR. OAL had increased expression and activity of the oxidant enzyme, NADPH oxidase, and its inhibition (apocynin) improved EDD, whereas NADPH oxidase in OCR was similar to Y. Manganese SOD activity and sirtuin1 expression were reduced in OAL (P<0.05), but restored to Y in OCR. Inflammatory cytokines were greater in OAL vs. YAL (P<0.05), but unaffected by CR. Carotid artery endothelium-independent dilation did not differ among groups. Short-term CR initiated in old age reverses age-associated vascular endothelial dysfunction by restoring NO bioavailability and reducing oxidation stress via reduced NADPH oxidase-mediated superoxide production and stimulation of anti-oxidant enzyme activity, and upregulates sirtuin1. PMID:20121721

  1. A non-calorie-restricted low-carbohydrate diet is effective as an alternative therapy for patients with type 2 diabetes.

    PubMed

    Yamada, Yoshifumi; Uchida, Junichi; Izumi, Hisa; Tsukamoto, Yoko; Inoue, Gaku; Watanabe, Yuichi; Irie, Junichiro; Yamada, Satoru

    2014-01-01

    Although caloric restriction is a widely used intervention to reduce body weight and insulin resistance, many patients are unable to comply with such dietary therapy for long periods. The clinical effectiveness of low-carbohydrate diets was recently described in a position statement of Diabetes UK and a scientific review conducted by the American Diabetes Association. However, randomised trials of dietary interventions in Japanese patients with type 2 diabetes are scarce. Therefore, the aim of this study was to examine the effects of a non-calorie-restricted, low-carbohydrate diet in Japanese patients unable to adhere to a calorie-restricted diet. The enrolled patients were randomly allocated to receive a conventional calorie-restricted diet or low-carbohydrate diet. The patients received consultations every two months from a registered dietician for six months. We compared the effects of the two dietary interventions on glycaemic control and metabolic profiles. The HbA1c levels decreased significantly from baseline to six months in the low-carbohydrate diet group (baseline 7.6±0.4%, six months 7.0±0.7%, p=0.03) but not in the calorie-restricted group (baseline 7.7±0.6%, six months 7.5±1.0%, n.s.), (between-group comparison, p=0.03). The patients in the former group also experienced improvements in their triglyceride levels, without experiencing any major adverse effects or a decline in the quality of life. Our findings suggest that a low-carbohydrate diet is effective in lowering the HbA1c and triglyceride levels in patients with type 2 diabetes who are unable to adhere to a calorie-restricted diet.

  2. The effect of a calorie-restricted diet on weight gain in short-term psychiatric inpatients receiving atypical antipsychotic medications.

    PubMed

    Jacobowitz, William; Derbabian, Barbara; Saunders, Anne

    2014-07-01

    This study attempted to evaluate the effect of a calorie-restricted diet on weight change in short-term acute care psychiatric patients receiving atypical antipsychotic medication. A descriptive correlational design utilizing chart review and a convenience sample of 100 participants was used. Fifty charts of patients hospitalized prior to the implementation of the calorie-restricted diet for those receiving atypical antipsychotic agents were compared to 50 charts of patients who received the diet. Weight changes in the two groups were compared relative to age, gender, length of time taking the medication, and the type of medication. The Mann-Whitney U test, Spearman's rank-correlation coefficient, and the two-way analysis of variance were used to conduct the analyses. The calorie-restricted diet was not significantly associated with a reduction in weight gain in participants who received any of the atypical antipsychotic agents except for olanzapine; therefore, findings indicate that the calorie-restricted diet may only be effective for patients receiving olanzapine.

  3. Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

    PubMed

    Kishi, Takuya; Hirooka, Yoshitaka; Nagayama, Tomomi; Isegawa, Kengo; Katsuki, Masato; Takesue, Ko; Sunagawa, Kenji

    2015-01-01

    In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

  4. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    USDA-ARS?s Scientific Manuscript database

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  5. Counting the calories: the role of specific nutrients in extension of life span by food restriction.

    PubMed

    Piper, Matthew D W; Mair, William; Partridge, Linda

    2005-05-01

    Reduction of food intake without malnourishment extends life span in many different organisms. The majority of work in this field has been performed in rodents where it has been shown that both restricting access to the entire diet and restricting individual dietary components can cause life-span extension. Thus, for insights into the mode of action of this intervention, it is of great interest to investigate the aspects of diet that are critical for life span extension. Further studies on the mechanisms of how food components modify life span are well suited to the model organism Drosophila melanogaster because of its short life span and ease of handling and containment. Therefore, we summarize practical aspects of implementing dietary restriction in this organism, as well as highlight the major advances already made. Delineation of the nutritional components that are critical for life-span extension will help to reveal the mechanisms by which it operates.

  6. Different gene expression of skin tissues between mice with weight controlled by either calorie restriction or physical exercise.

    PubMed

    Lu, Jia; Xie, Linglin; Sylvester, Jessica; Wang, Jiasong; Bai, Jianfa; Baybutt, Richard; Wang, Weiqun

    2007-04-01

    Cancer prevention by weight control via dietary calorie restriction (DCR) and/or exercise has been demonstrated in animal models. To understand the underlying mechanisms, we compared phorbol ester (TPA)-induced gene expression profiles in DCR- or exercise-treated mouse skin tissues. SENCAR mice were randomly assigned to one of the following groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AE), exercise but pair-fed at the amount of the control (PE), and 20% DCR. After 10 weeks, both body weight and fat composition significantly decreased in the DCR and PE groups compared with the controls. Weight loss was not observed in the AE group due, at least in part, to increased food intake. Among 39,000 transcripts with 45,101 probe sets measured by Affymetrix microarray, we identified 411, 110, and 67 genes that showed >or=1.5-fold and significant changes by DCR, AE, and PE, respectively. Gene ontology showed a profound impact on gene expression by DCR in 21 biologic process categories. Although PE and AE had a moderate impact on gene expression, the similarity of gene expression pattern altered by PE was relatively closer to DCR, whereas AE was closer to the control. The results of 22 cancer-related gene expression patterns, especially for certain oncogenes, further supported that PE appeared to be a better alternative than AE to DCR-like cancer prevention. The impact on gene expression pattern was associated with the effect on weight loss (i.e., DCR > PE > AE). Overall, this study demonstrated for the first time that weight control via decreasing energy intake or increasing energy expenditure resulted in the different modes of gene expression. DCR showed profound inhibitory impact on the expression of genes relevant to cancer risks. Furthermore, exercise along with limited calorie intake appears to be a better method for reducing weight and cancer risk compared with exercise alone.

  7. DISTINCT EFFECTS OF CALORIE RESTRICTION AND EXERCISE ON MAMMARY GLAND GENE EXPRESSION IN C57BL/6 MICE

    PubMed Central

    Padovani, Michela; Lavigne, Jackie A.; Chandramouli, Gadisetti V.R.; Perkins, Susan N.; Barrett, J. Carl; Hursting, Stephen D.; Bennett, L. Michelle; Berrigan, David

    2009-01-01

    Energy balance, including diet, weight, adiposity, and physical activity is associated with carcinogenesis. Epidemiological studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both pre-and postmenopausal breast cancer patients. Thus, understanding energy balance modulation’s influence on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms linking energy balance and breast cancer. In a six week long study, female C57BL/6 mice (9 weeks old) were randomized into four groups: 1) food consumed ad libitum (AL); 2) AL with access to running wheels (AL+EX); 3) 30% Calorie Restricted (CR); and 4) 30% CR with access to running wheels (CR+EX). CR mice received 70% of calories but 100% of all other nutrients compared to AL mice. Diet and exercise treatments individually and combined, had significant effects on body composition and physical activity. Affymetrix oligo-microarrays were used to explore changes in gene expression patterns in total RNA samples from excised whole mammary glands. Contrasting AL versus CR resulted in 425 statistically significant expression changes whereas AL versus AL +EX resulted in 45 changes, with only 3 changes included the same genes, indicating that CR and EX differentially influence expression patterns in non-cancerous mammary tissue. Differential expression was observed in genes related to breast cancer stem cells, the epithelial -mesenchymal transition, and the growth and survival of breast cancer cells. Thus, CR and EX appear to exert their effects on mammary carcinogenesis through distinct pathways. PMID:19952363

  8. Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.

    PubMed

    Padovani, Michela; Lavigne, Jackie A; Chandramouli, Gadisetti V R; Perkins, Susan N; Barrett, J Carl; Hursting, Stephen D; Bennett, L Michelle; Berrigan, David

    2009-12-01

    Energy balance, including diet, weight, adiposity, and physical activity, is associated with carcinogenesis. Epidemiologic studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both premenopausal and postmenopausal breast cancer patients. Thus, understanding the influence of energy balance modulation on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms linking energy balance and breast cancer. In a 6-week-long study, female C57BL/6 mice (9-week-old) were randomized into four groups: (a) food consumed ad libitum (AL), (b) AL with access to running wheels (AL+EX), (c) 30% calorie restricted (CR), and (d) 30% CR with access to running wheels (CR+EX). CR mice received 70% of calories but 100% of all other nutrients compared with AL mice. Diet and exercise treatments, individually and combined, had significant effects on body composition and physical activity. Affymetrix oligomicroarrays were used to explore changes in gene expression patterns in total RNA samples from excised whole mammary glands. Contrasting AL versus CR resulted in 425 statistically significant expression changes, whereas AL versus AL+EX resulted in 45 changes, with only 3 changes included among the same genes, indicating that CR and EX differentially influence expression patterns in noncancerous mammary tissue. Differential expression was observed in genes related to breast cancer stem cells, the epithelial-mesenchymal transition, and the growth and survival of breast cancer cells. Thus, CR and EX seem to exert their effects on mammary carcinogenesis through distinct pathways.

  9. Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials.

    PubMed

    Martin, Corby K; Das, Sai Krupa; Lindblad, Lauren; Racette, Susan B; McCrory, Megan A; Weiss, Edward P; Delany, James P; Kraus, William E

    2011-04-01

    The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5-29.9 kg/m² adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE - RMR - 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity.

  10. Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials

    PubMed Central

    Das, Sai Krupa; Lindblad, Lauren; Racette, Susan B.; McCrory, Megan A.; Weiss, Edward P.; DeLany, James P.; Kraus, William E.

    2011-01-01

    The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5–29.9 kg/m2) adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE − RMR − 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity. PMID:21292847

  11. Weight loss by calorie restriction versus bariatric surgery differentially regulates the HPA axis in male rats

    PubMed Central

    Grayson, Bernadette E.; Hakala-Finch, Andrew P.; Kekulawala, Melani; Laub, Holly; Egan, Ann E.; Ressler, Ilana B.; Woods, Stephen C.; Herman, James P.; Seeley, Randy J.; Benoit, Stephen C.; Ulrich-Lai, Yvonne M.

    2015-01-01

    Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in 5 groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n=7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n=11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n=11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n=11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n=12). Compared to Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentrations and increased hypothalamic corticotropin releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results suggest that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches. PMID:25238021

  12. Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan.

    PubMed

    Cai, Weijing; He, John C; Zhu, Li; Chen, Xue; Zheng, Feng; Striker, Gary E; Vlassara, Helen

    2008-08-01

    We previously showed that the content of advanced glycation end products (AGEs) in the diet correlates with serum AGE levels, oxidant stress (OS), organ dysfunction, and lifespan. We now show that the addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE mouse chow increased serum levels of AGEs and OS, demonstrating that dietary AGEs are oxidants that can induce systemic OS. OS predisposes to the development of cardiovascular and chronic kidney diseases; calorie restriction (CR) is the most studied means to decrease OS, increase longevity, and reduce OS-related organ damage in mammals. Because reduction of food intake also decreases oxidant AGE s intake, we asked whether the beneficial effects of CR in mammals are related to the restriction of oxidants or energy. Pair-fed mice were provided either a CR diet or a high-AGE CR diet in which AGEs were elevated by brief heat treatment (CR-high). Old CR-high mice developed high levels of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1 and GSH/GSSG levels, insulin resistance, marked myocardial and renal fibrosis, and shortened lifespan. In contrast, old CR mice had low OS, p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with longer lifespan. Therefore, the beneficial effects of a CR diet may be partly related to reduced oxidant intake, a principal determinant of oxidant status in aging mice, rather than decreased energy intake.

  13. Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro.

    PubMed

    de Cabo, Rafael; Liu, Lijuan; Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M

    2015-03-01

    The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.

  14. Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro

    PubMed Central

    Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M.

    2015-01-01

    The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes. (185 words). PMID:25855056

  15. Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer

    PubMed Central

    Devlin, Kaylyn L.; Sanford, Tiffany; Harrison, Lauren M.; LeBourgeois, Paul; Lashinger, Laura M.; Mambo, Elizabeth; Hursting, Stephen D.

    2016-01-01

    MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction. PMID:27433802

  16. Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer.

    PubMed

    Devlin, Kaylyn L; Sanford, Tiffany; Harrison, Lauren M; LeBourgeois, Paul; Lashinger, Laura M; Mambo, Elizabeth; Hursting, Stephen D

    2016-01-01

    MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction.

  17. A calorie-restriction diet supplemented with fish oil and high-protein powder is associated with reduced severity of metabolic syndrome in obese women.

    PubMed

    Su, H-Y; Lee, H-C; Cheng, W-Y; Huang, S-Y

    2015-03-01

    The prevalence of metabolic syndrome (MetS) and obesity has increased worldwide, as well as in Taiwan, particularly in women aged>40 years. The purpose of this study was to elucidate the effects of a calorie-restriction diet (CR) supplemented with protein and n-3 polyunsaturated fatty acids (PUFAs) on women with MetS. A total of 143 eligible female participants were recruited and assigned to four dietary interventions such as 1500-kcal CR, calorie-restriction meal-replacement diet (CRMR), calorie-restriction diet with fish oil supplementation (CRF) and calorie-restriction meal-replacement diet with fish oil supplementation (CRMRF). The changes in anthropometric measures, metabolic profiles, inflammatory response and the Z-score of severity of MetS were evaluated. Among 143 female MetS patients enrolled, 136 patients completed the 12-week study. After the 12-week dietary interventions, we observed reductions in body weight (BW), body mass index (BMI) and waist circumference (WC) in all groups. BMI and triglyceride (TG) levels decreased significantly in the CRMR, CRF and CRMRF groups, but not in the CR group. The homeostasis model assessment of insulin resistance (HOMA-IR) had significantly improved in all four groups, and the levels of interleukin-6 (IL-6) and C-reactive protein (CRP) had significantly decreased in the CRF and CRMRF groups. Following the interventions, the changes in waist circumference (WC), mean arterial pressure (MAP), fasting blood glucose (FBG), TGs, HOMA-IR, CRP and IL-6 significantly correlated with the reductions in Z-score of MetS severity. Our study results indicate that a calorie-restriction dietary intervention combined with various macronutrients can reduce the severity of MetS in women and increase recovery from MetS by almost twofold in comparison with a CR alone.

  18. Conjectures on some curious connections among social status, calorie restriction, hunger, fatness, and longevity.

    PubMed

    Kaiser, Kathryn A; Smith, Daniel L; Allison, David B

    2012-08-01

    Many animal and human studies show counterintuitive effects of environmental influences on energy balance and life span. Relatively low social and/or economic status seems to be associated with and produce greater adiposity, and reduced provision (e.g., caloric restriction) of food produces greater longevity. We suggest that a unifying factor may be perceptions of the environment as "energetically insecure" and inhospitable to reproduction, which may in turn provoke adiposity-increasing and longevity-extending mechanisms. We elaborate on two main aspects of resources (or the perceptions thereof) on body weight and longevity. We first discuss the effects of social dominance on body weight regulation in human and animal models. Second, we examine models of the interactions between caloric restriction, body composition, and longevity. Finally, we put forth a relational model of the influences of differing environmental cues on body composition and longevity. © 2012 New York Academy of Sciences.

  19. Conjectures on some curious connections among social status, calorie restriction, hunger, fatness, and longevity

    PubMed Central

    Kaiser, Kathryn A; Smith, Daniel L; Allison, David B

    2012-01-01

    Many animal and human studies show counterintuitive effects of environmental influences on energy balance and life span. Relatively low social and/or economic status seems to be associated with and produce greater adiposity, and reduced provision (e.g., caloric restriction) of food produces greater longevity. We suggest that a unifying factor may be perceptions of the environment as “energetically insecure” and inhospitable to reproduction, which may in turn provoke adiposity-increasing and longevity-extending mechanisms. We elaborate on two main aspects of resources (or the perceptions thereof) on body weight and longevity. We first discuss the effects of social dominance on body weight regulation in human and animal models. Second, we examine models of the interactions between caloric restriction, body composition, and longevity. Finally, we put forth a relational model of the influences of differing environmental cues on body composition and longevity. PMID:22834696

  20. Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias.

    PubMed

    MacDonald, Leah; Radler, Morgan; Paolini, Antonio G; Kent, Stephen

    2011-07-01

    Calorie restriction (CR) has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25% (CR25%) or restricted 50% (CR50%) in food intake for 28 days and injected with 50 μg/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50% for 28 days, and hypothalamic mRNA expression of inhibitory factor κB-α (IκB-α), cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50% mice did not develop fevers, whereas the CR25% mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25% and CR50% mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50% animals preinjection compared with controls. The CR50% mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and IκB-α expression in CR50% animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways.

  1. Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

    PubMed Central

    Larson-Meyer, D. Enette; Heilbronn, Leonie K.; Redman, Leanne M.; Newcomer, Bradley R.; Frisard, Madlyn I.; Anton, Steve; Smith, Steven R.; Maplstat, Anthony Alfonso; Ravussin, Eric

    2009-01-01

    OBJECTIVE The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intra-hepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (Si) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction +12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and Si were assessed at baseline and month 6. RESULTS At baseline, FCS was related to VAT and IHL (P < 0.05) but not to IMCL. FCS was also the strongest determinant of Si (P < 0.01). Weight loss at month 6 was 1 ± 1% (control, mean ± SE), 10 ± 1% (CR), 10 ± 1% (CREX), and 14 ± 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P < 0.01), but IMCL was unchanged. Si was increased at month 6 (P = 0.05) in the CREX (37 ± 18%) and LCD (70 ± 34%) groups (P < 0.05) and tended to increase in the CR group (40 ± 20%, P = 0.08). Together the improvements in Si were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS. CONCLUSIONS Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend. PMID:16732018

  2. Exercise with calorie restriction improves insulin sensitivity and glycogen synthase activity in obese postmenopausal women with impaired glucose tolerance

    PubMed Central

    Ortmeyer, Heidi K.; Sorkin, John D.

    2012-01-01

    Our objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in normal (NGT) vs. impaired glucose-tolerant (IGT) obese postmenopausal women and to determine whether an increase in insulin activation of GS is associated with an improvement in insulin sensitivity (M) following calorie restriction (CR) and/or aerobic exercise plus calorie restriction (AEX + CR) in women with NGT and IGT. We did a longitudinal, clinical intervention study of CR compared with AEX + CR. Overweight and obese women, 49–76 yr old, completed 6 mo of CR (n = 46) or AEX + CR (n = 50) with V̇o2 max, body composition, and glucose tolerance testing. Hyperinsulinemic euglycemic (80 mU·m−2·min−1) clamps (n = 73) and skeletal muscle biopsies (before and during clamp) (n = 58) were performed before and after the interventions (n = 50). After 120 min of hyperinsulinemia during the clamp, GS fractional activity and insulin's effect to increase GS fractional activity (insulin − basal) were significantly lower in IGT vs. NGT (P < 0.01) at baseline. GS total activity increased during the clamp in NGT (P < 0.05), but not IGT, at baseline. CR and AEX + CR resulted in a significant 8% weight loss with reductions in total fat mass, visceral fat, subcutaneous fat, and intramuscular fat. Overall, M increased (P < 0.01), and the change in M (postintervention − preintervention) was associated with the change in insulin-stimulated GS fractional activity (partial r = 0.44, P < 0.005). In IGT, the change (postintervention − preintervention) in insulin-stimulated GS total activity was greater following AEX + CR than CR alone (P < 0.05). In IGT, insulin-stimulated GS-independent (P < 0.005) and fractional activity (P = 0.06) increased following AEX + CR. We conclude that the greatest benefits at the whole body and cellular level (insulin activation of GS) in older women at highest risk for diabetes are derived from a lifestyle intervention that

  3. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    PubMed Central

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent. PMID:25895126

  4. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

    PubMed Central

    Fontana, Luigi; Meyer, Timothy E.; Klein, Samuel; Holloszy, John O.

    2004-01-01

    Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 ± 1.9 vs. 25.9 ± 3.2 kg/m2; percent body fat, 8.7 ± 7% vs. 24 ± 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was ≈40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT. PMID:15096581

  5. Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats

    PubMed Central

    Wang, Haiyan; Arias, Edward B.

    2016-01-01

    Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr309 and Ser474 along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642 and Ser588, filamin C on Ser2213 and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals. PMID:26739650

  6. Short-term calorie restriction protects against renal senescence of aged rats by increasing autophagic activity and reducing oxidative damage.

    PubMed

    Ning, Yi-Chun; Cai, Guang-Yan; Zhuo, Li; Gao, Jian-Jun; Dong, Dan; Cui, Shaoyuan; Feng, Zhe; Shi, Suo-Zhu; Bai, Xue-Yuan; Sun, Xue-Feng; Chen, Xiang-Mei

    2013-01-01

    To explore the effect of short-term calorie restriction (CR) on renal aging, 8-week CR with 60% of the food intake of the ad libitum group was administered in 25-month-old male Sprague-Dawley rats. Aged rats subjected to short-term CR had lower body weight, level of triglycerides and ratio of urine protein to urine creatinine, respectively. Short-term CR blunted the increased glomerular volume, the degree of fibrosis, p16 and the positive rate of senescence-associated β-galactosidase staining of the kidneys in old ad libitum group. Light chain 3/Atg8 as an autophagy marker exhibited a marked decline in aged kidneys, which was increased by short-term CR. The levels of p62/SQSTM1 and polyubiquitin aggregates, which were increased in older kidneys, were blunted by short-term CR. Short-term CR retarded the level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage. Moreover, we found an increased level of SIRT1 and AMPK, and a decreased level of mTOR in aged kidneys after short-term CR. These results suggested that short-term CR could be considered as a potential intervention for retardation of renal senescence by increasing autophagy and subsequently reducing oxidative damage. Three master regulators of energy metabolism, SIRT1, AMPK and mTOR are associated with these effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. The Influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction

    PubMed Central

    Chen, Yana; Hagopian, Kevork; Bibus, Douglas; Villalba, José M.; López-Lluch, Guillermo; Navas, Plácido; Kim, Kyoungmi; Ramsey, Jon J.

    2014-01-01

    Summary Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95% (control) or 60% (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H2O2production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CR-induced decreases in ROS production. PMID:24182343

  8. The Influence of Dietary Lipid Composition on Skeletal Muscle Mitochondria From Mice Following 1 Month of Calorie Restriction

    PubMed Central

    Chen, Yana; Hagopian, Kevork; McDonald, Roger B.; Bibus, Douglas; López-Lluch, Guillermo; Villalba, José M.; Navas, Plácido

    2012-01-01

    To investigate the role mitochondrial membrane lipids play in the actions of calorie restriction (CR), C57BL/6 mice were assigned to four groups (control and three 40% CR groups) and fed diets containing soybean oil (also in the control diet), fish oil, or lard. The fatty acid composition of the major mitochondrial phospholipid classes, proton leak, and H2O2 production were measured in muscle mitochondria following 1 month of CR. The results indicate that phospholipid fatty acids reflected the polyunsaturated fatty acid profile of the dietary lipid sources. Capacity for Complex I– and III–linked H2O2 production was decreased with CR, although there was no difference between CR groups. The CR lard group had lower proton leak than all other groups. The results indicate that a decreased degree of unsaturation in muscle mitochondrial membranes is not required for reduced H2O2 production with CR. However, dietary lipids do have some influence on proton leak with CR. PMID:22503990

  9. The Effect of Long Term Calorie Restriction on in Vivo Hepatic Proteostatis: A Novel Combination of Dynamic and Quantitative Proteomics

    PubMed Central

    Price, John C.; Khambatta, Cyrus F.; Li, Kelvin W.; Bruss, Matthew D.; Shankaran, Mahalakshmi; Dalidd, Marcy; Floreani, Nicholas A.; Roberts, Lindsay S.; Turner, Scott M.; Holmes, William E.; Hellerstein, Marc K.

    2012-01-01

    Calorie restriction (CR) promotes longevity. A prevalent mechanistic hypothesis explaining this effect suggests that protein degradation, including mitochondrial autophagy, is increased with CR, removing damaged proteins and improving cellular fitness. At steady state, increased catabolism must be balanced by increasing mitochondrial biogenesis and protein synthesis, resulting in faster protein replacement rates. To test this hypothesis, we measured replacement kinetics and relative concentrations of hundreds of proteins in vivo in long-term CR and ad libitum-fed mice using metabolic 2H2O-labeling combined with the Stable Isotope Labeling in Mammals protocol and LC-MS/MS analysis of mass isotopomer abundances in tryptic peptides. CR reduced absolute synthesis and breakdown rates of almost all measured hepatic proteins and prolonged the half-lives of most (∼80%), particularly mitochondrial proteins (but not ribosomal subunits). Proteins with related functions exhibited coordinated changes in relative concentration and replacement rates. In silico expression pathway interrogation allowed the testing of potential regulators of altered network dynamics (e.g. peroxisome proliferator-activated receptor gamma coactivator 1-alpha). In summary, our combination of dynamic and quantitative proteomics suggests that long-term CR reduces mitochondrial biogenesis and mitophagy. Our findings contradict the theory that CR increases mitochondrial protein turnover and provide compelling evidence that cellular fitness is accompanied by reduced global protein synthetic burden. PMID:22984287

  10. Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats

    PubMed Central

    Khraiwesh, Husam; López-Domínguez, José A.; del Río, Lucía Fernández; Gutierrez-Casado, Elena; López-Lluch, Guillermo; Navas, Plácido; de Cabo, Rafael; Ramsey, Jon J.; Burón, María I.; Villalba, José M.; González-Reyes, José A.

    2014-01-01

    In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18 months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls),fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice. PMID:24704714

  11. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.

    PubMed

    Catenacci, Victoria A; Pan, Zhaoxing; Ostendorf, Danielle; Brannon, Sarah; Gozansky, Wendolyn S; Mattson, Mark P; Martin, Bronwen; MacLean, Paul S; Melanson, Edward L; Troy Donahoo, William

    2016-09-01

    To evaluate the safety and tolerability of alternate-day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) with those produced by a standard weight loss diet, moderate daily caloric restriction (CR). Adults with obesity (BMI ≥30 kg/m(2) , age 18-55) were randomized to either zero-calorie ADF (n = 14) or CR (-400 kcal/day, n = 12) for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up. No adverse effects were attributed to ADF, and 93% completed the 8-week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between-group differences in change in weight (mean ± SE; ADF -8.2 ± 0.9 kg, CR -7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF. ADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids, and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention. © 2016 The Obesity Society.

  12. The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice.

    PubMed

    Wiesenborn, Denise S; Menon, Vinal; Zhi, Xu; Do, Andrew; Gesing, Adam; Wang, Zhihui; Bartke, Andrzej; Altomare, Deborah A; Masternak, Michal M

    2014-10-01

    Long-living Ames dwarf (df/df) mice are homozygous for a mutation of the Prop1(df) gene. As a result, mice are deficient in growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). In spite of the hormonal deficiencies, df/df mice live significantly longer and healthier lives compared to their wild type siblings. We studied the effects of calorie restriction (CR) on the expression of insulin signaling genes in skeletal muscle and adipose tissue of normal and df/df mice. The analysis of genes expression showed that CR differentially affects the insulin signaling pathway in these insulin target organs. Moreover, results obtained in both normal and Ames dwarf mice indicate more direct effects of CR on insulin signaling genes in adipose tissue than in skeletal muscle. Interestingly, CR reduced the protein levels of adiponectin in the epididymal adipose tissue of normal and Ames dwarf mice, while elevating adiponectin levels in skeletal muscle and plasma of normal mice only. In conclusion, our findings suggest that both skeletal muscle and adipose tissue are important mediators of insulin effects on longevity. Additionally, the results revealed divergent effects of CR on expression of genes in the insulin signaling pathway of normal and Ames dwarf mice.

  13. The antihypertensive effect of calorie restriction in obese adolescents: dissociation of effects on erythrocyte countertransport and cotransport.

    PubMed

    Weder, A B; Torretti, B A; Katch, V L; Rocchini, A P

    1984-10-01

    Measures of maximal rates of lithium-sodium countertransport and frusemide-sensitive sodium and potassium cotransport have been proposed as biochemical markers for human essential hypertension. The stability of these functions over time within the same individuals has led to the suggestion that maximal transport capacities are genetically determined. The present study confirms the reproducibility of functional assays of countertransport and cotransport in human erythrocytes after overnight storage and over a six-month period in normal volunteers and provides estimates of the magnitude of technical error for each assay. A long-term dietary intervention study in a group of obese adolescents demonstrated marked increases in erythrocyte sodium levels and maximal frusemide-sensitive sodium and potassium fluxes but no changes in cell potassium or water and no effect on lithium-sodium countertransport. A correlation between the decrease in percentage of body fat and the increase in cell sodium content suggests a link between the metabolic effects of dieting and control of erythrocyte cation handling. Although the mechanism linking dietary calorie restriction and changes in erythrocyte cation metabolism is unknown, evaluation of body weight, and especially recent weight loss, is important in studies of erythrocyte transport. Conclusions regarding genetic contributions to the activities of lithium-sodium countertransport and sodium-potassium cotransport systems will be strengthened by clarification of environmental regulators.

  14. The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension.

    PubMed

    Easlon, Erin; Tsang, Felicia; Dilova, Ivanka; Wang, Chen; Lu, Shu-Ping; Skinner, Craig; Lin, Su-Ju

    2007-03-02

    Calorie restriction (CR) extends life span in a wide variety of species. Recent studies suggest that an increase in mitochondrial metabolism mediates CR-induced life span extension. Here we present evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase complex, is a novel metabolic longevity factor in the CR pathway. Deleting the LAT1 gene abolishes life span extension induced by CR. Overexpressing Lat1 extends life span, and this life span extension is not further increased by CR. Similar to CR, life span extension by Lat1 overexpression largely requires mitochondrial respiration, indicating that mitochondrial metabolism plays an important role in CR. Interestingly, Lat1 overexpression does not require the Sir2 family to extend life span, suggesting that Lat1 mediates a branch of the CR pathway that functions in parallel to the Sir2 family. Lat1 is also a limiting longevity factor in nondividing cells in that overexpressing Lat1 extends cell survival during prolonged culture at stationary phase. Our studies suggest that Lat1 overexpression extends life span by increasing metabolic fitness of the cell. CR may therefore also extend life span and ameliorate age-associated diseases by increasing metabolic fitness through regulating central metabolic enzymes.

  15. Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging: A descriptive study

    PubMed Central

    Tomiyama, A. Janet; Milush, Jeffrey M.; Lin, Jue; Flynn, James M.; Kapahi, Pankaj; Verdin, Eric; Sinclair, Elizabeth; Melov, Simon; Epel, Elissa S.

    2017-01-01

    BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched “healthy” Body Mass Index (BMI) and “overweight”/“obese” BMI groups. RESULTS: Long-term human CR practitioners had lower BMI (p <  0.001) and fasting glucose (p <  0.001), as expected. They showed similar frequencies of pre-senescent cells (CD8+CD28– T cells and CD57 and PD-1 expressing T cells) to the comparison groups. Even after adjusting for covariates, including cytomegalovirus status, we observed shorter peripheral blood mononuclear cell telomeres in the CR group (p = 0.012) and no difference in granulocyte telomeres between groups (p = 0.42). CONCLUSIONS: We observed no clear evidence that CR as it is currently practiced in humans delays immune aging related to telomere length or T cell immunosenescent markers PMID:28447069

  16. Genomic lesions and colorectal carcinogenesis: the effects of protein-calorie restriction and inulin supplementation on deficiency statuses.

    PubMed

    Cantero, W B; Takahachi, N A; Mauro, M O; Pesarini, J R; Rabacow, A P M; Antoniolli, A C M B; Oliveira, R J

    2015-03-27

    The present study investigated the effects of restricting protein and calories and supplementation of inulin, a fiber comprising a linear type of polydisperse carbohydrates composed primarily of fructil-fructose bonds (β-(2→1), on the deficiency statuses of animals in which genomic lesion development and colorectal carcinogenesis had been induced. This experiment involved adult male Swiss mice (N = 11/group). The experimental groups were as follows: Negative Control (vehicle), Positive Control, 1,2-dimethylhydrazine (DMH), Inulin, and Associate. DMH, which promoted colorectal cancer, was administered intraperitoneally in 4 20-mg/kg body weight (bw) doses during a 2-week period; inulin was administered orally at a daily dose of 50 mg/kg bw. Each group was bifurcated; half of each group was fed a normal protein diet and the other half was fed a low-protein diet. The results indicated that a correlation existed between malnutrition and an increased frequency of genomic lesions but that malnutrition did not predispose animals to colorectal cancer development. Inulin exhibited genotoxic activity, which requires further investigation, and low anti-genotoxic activity. Moreover, inulin reduced the levels of intestinal carcinogenesis biomarkers in both malnourished and healthy animals. These data suggest that inulin holds therapeutic potential and is a strong candidate for inclusion among the functional foods used for cancer prevention in both properly nourished and malnourished individuals.

  17. The influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction.

    PubMed

    Chen, Y; Hagopian, K; Bibus, D; Villalba, J M; López-Lluch, G; Navas, P; Kim, K; Ramsey, J J

    2014-01-01

    Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95 % (control) or 60 % (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H(2)O(2) production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CR-induced decreases in ROS production.

  18. Hyperinsulinemia/Diabetes, Hearing, and Aging in the University of Wisconsin Calorie Restriction Monkeys

    PubMed Central

    Fowler, Cynthia G.; Chiasson, Kirstin Beach; Colman, Ricki; Kemnitz, Joseph W.; Beasley, T. Mark; Weindruch, Richard

    2015-01-01

    The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211–8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8–17 dB larger in the NL group than in the HID and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5–8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at risk

  19. Enhanced Energy Metabolism Contributes to the Extended Life Span of Calorie-restricted Caenorhabditis elegans*

    PubMed Central

    Yuan, Yiyuan; Kadiyala, Chandra S.; Ching, Tsui-Ting; Hakimi, Parvin; Saha, Sudipto; Xu, Hua; Yuan, Chao; Mullangi, Vennela; Wang, Liwen; Fivenson, Elayne; Hanson, Richard W.; Ewing, Rob; Hsu, Ao-Lin; Miyagi, Masaru; Feng, Zhaoyang

    2012-01-01

    Caloric restriction (CR) markedly extends life span and improves the health of a broad number of species. Energy metabolism fundamentally contributes to the beneficial effects of CR, but the underlying mechanisms that are responsible for this effect remain enigmatic. A multidisciplinary approach that involves quantitative proteomics, immunochemistry, metabolic quantification, and life span analysis was used to determine how CR, which occurs in the Caenorhabditis elegans eat-2 mutants, modifies energy metabolism of the worm, and whether the observed modifications contribute to the CR-mediated physiological responses. A switch to fatty acid metabolism as an energy source and an enhanced rate of energy metabolism by eat-2 mutant nematodes were detected. Life span analyses validated the important role of these previously unknown alterations of energy metabolism in the CR-mediated longevity of nematodes. As observed in mice, the overexpression of the gene for the nematode analog of the cytosolic form of phosphoenolpyruvate carboxykinase caused a marked extension of the life span in C. elegans, presumably by enhancing energy metabolism via an altered rate of cataplerosis of tricarboxylic acid cycle anions. We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in life span regulation; this mechanism may be conserved across phylogeny. PMID:22810224

  20. Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice.

    PubMed

    Varady, K A; Roohk, D J; McEvoy-Hein, B K; Gaylinn, B D; Thorner, M O; Hellerstein, M K

    2008-06-01

    Calorie restriction (CR) and alternate-day fasting (ADF) reduce cancer risk and reduce cell proliferation rates. Whether modified ADF regimens (i.e., allowing a portion of energy needs to be consumed on the fast day) work, as well as true ADF or CR to reduce global cell proliferation rates, remains unresolved. Here, we measured the effects of true ADF, modified ADF, and daily CR on cell proliferation rates in mice. Thirty female C57BL/6J mice were randomized to one of five interventions for 4 wk: 1) CR-25% (25% reduction in daily energy intake), 2) ADF-75% (75% reduction on fast day), 3) ADF-85% (85% reduction on fast day), 4) ADF-100% (100% reduction on fast day), and 5) control (ad libitum intake). Body weights of the ADF groups did not differ from controls, whereas the CR-25% group weighed less than all other groups posttreatment. Epidermal cell proliferation decreased (P<0.01) by 29, 20, and 31% in the CR-25%, ADF-85% and ADF-100% groups, respectively, relative to controls. Proliferation rates of splenic T cells were reduced (P<0.01) by 37, 32, and 31% in the CR-25%, ADF-85%, and ADF-100% groups, respectively, and mammary epithelial cell proliferation was 70, 65, and 62% lower (P<0.01), compared with controls. Insulin-like growth factor-1 levels were reduced (P<0.05) in the CR-25% and ADF-100% groups only. In summary, modified ADF, allowing the consumption of 15% of energy needs on the restricted intake day, decreases global cell proliferation similarly as true ADF and daily CR without reducing body weight.

  1. Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction.

    PubMed

    Chiba, Takuya; Tsuchiya, Tomoshi; Komatsu, Toshimitsu; Mori, Ryoichi; Hayashi, Hiroko; Shimano, Hitoshi; Spindler, Stephen R; Shimokawa, Isao

    2010-10-15

    Suppression of the growth hormone/insulin-like growth factor-I pathway in Ames dwarf (DF) mice, and caloric restriction (CR) in normal mice extends lifespan and delays the onset of age-related disorders. In combination, these interventions have an additive effect on lifespan in Ames DF mice. Therefore, common signaling pathways regulated by DF and CR could have additive effects on longevity. In this study, we tried to identity the signaling mechanism and develop a system to assess pro-longevity status in cells and mice. We previously identified genes up-regulated in the liver of DF and CR mice by DNA microarray analysis. Motif analysis of the upstream sequences of those genes revealed four major consensus sequence motifs, which have been named dwarfism and calorie restriction-responsive elements (DFCR-REs). One of the synthesized sequences bound to hepatocyte nuclear factor-4α (HNF-4α), an important transcription factor involved in liver metabolism. Furthermore, using this sequence information, we developed a highly sensitive bioassay to identify chemicals mimicking the anti-aging effects of CR. When the reporter construct, containing an element upstream of a secreted alkaline phosphatase (SEAP) gene, was co-transfected with HNF-4α and its regulator peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α), SEAP activity was increased compared with untransfected controls. Moreover, transient transgenic mice established using this construct showed increased SEAP activity in CR mice compared with ad libitum-fed mice. These data suggest that because of its rapidity, ease of use, and specificity, our bioassay will be more useful than the systems currently employed to screen for CR mimetics, which mimic the beneficial effects of CR. Our system will be particularly useful for high-throughput screening of natural and synthetic candidate molecules. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

    PubMed

    Larson-Meyer, D Enette; Newcomer, Bradley R; Heilbronn, Leonie K; Volaufova, Julia; Smith, Steven R; Alfonso, Anthony J; Lefevre, Michael; Rood, Jennifer C; Williamson, Donald A; Ravussin, Eric

    2008-06-01

    Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

  3. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women

    PubMed Central

    2012-01-01

    Background Intermittent fasting (IF; severe restriction 1 d/week) facilitates weight loss and improves coronary heart disease (CHD) risk indicators. The degree to which weight loss can be enhanced if IF is combined with calorie restriction (CR) and liquid meals, remains unknown. Objective This study examined the effects of IF plus CR (with or without a liquid diet) on body weight, body composition, and CHD risk. Methods Obese women (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet. The trial had two phases: 1) 2-week weight maintenance period, and 2) 8-week weight loss period. Results Body weight decreased more (P = 0.04) in the IFCR-L group (3.9 ± 1.4 kg) versus the IFCR-F group (2.5 ± 0.6 kg). Fat mass decreased similarly (P < 0.0001) in the IFCR-L and IFCR-F groups (2.8 ± 1.2 kg and 1.9 ± 0.7 kg, respectively). Visceral fat was reduced (P < 0.001) by IFCR-L (0.7 ± 0.5 kg) and IFCR-F (0.3 ± 0.5 kg) diets. Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01), while heart rate, glucose, insulin, and homocysteine decreased (P < 0.05), in the IFCR-L group only. Conclusion These findings suggest that IF combined with CR and liquid meals is an effective strategy to help obese women lose weight and lower CHD risk. PMID:23171320

  4. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women.

    PubMed

    Klempel, Monica C; Kroeger, Cynthia M; Bhutani, Surabhi; Trepanowski, John F; Varady, Krista A

    2012-11-21

    Intermittent fasting (IF; severe restriction 1 d/week) facilitates weight loss and improves coronary heart disease (CHD) risk indicators. The degree to which weight loss can be enhanced if IF is combined with calorie restriction (CR) and liquid meals, remains unknown. This study examined the effects of IF plus CR (with or without a liquid diet) on body weight, body composition, and CHD risk. Obese women (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet. The trial had two phases: 1) 2-week weight maintenance period, and 2) 8-week weight loss period. Body weight decreased more (P = 0.04) in the IFCR-L group (3.9 ± 1.4 kg) versus the IFCR-F group (2.5 ± 0.6 kg). Fat mass decreased similarly (P < 0.0001) in the IFCR-L and IFCR-F groups (2.8 ± 1.2 kg and 1.9 ± 0.7 kg, respectively). Visceral fat was reduced (P < 0.001) by IFCR-L (0.7 ± 0.5 kg) and IFCR-F (0.3 ± 0.5 kg) diets. Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01), while heart rate, glucose, insulin, and homocysteine decreased (P < 0.05), in the IFCR-L group only. These findings suggest that IF combined with CR and liquid meals is an effective strategy to help obese women lose weight and lower CHD risk.

  5. Glycine supplementation during calorie restriction accelerates fat loss and protects against further muscle loss in obese mice.

    PubMed

    Caldow, Marissa K; Ham, Daniel J; Godeassi, Daniel P; Chee, Annabel; Lynch, Gordon S; Koopman, René

    2016-10-01

    Calorie restriction (CR) reduces co-morbidities associated with obesity, but also reduces lean mass thereby predisposing people to weight regain. Since we demonstrated that glycine supplementation can reduce inflammation and muscle wasting, we hypothesized that glycine supplementation during CR would preserve muscle mass in mice. High-fat fed male C57BL/6 mice underwent 20 days CR (40% reduced calories) supplemented with glycine (1 g/kg/day; n = 15, GLY) or l-alanine (n = 15, ALA). Body composition and glucose tolerance were assessed and hindlimb skeletal muscles and epididymal fat were collected. Eight weeks of a high-fat diet (HFD) induced obesity and glucose intolerance. CR caused rapid weight loss (ALA: 20%, GLY: 21%, P < 0.01), reduced whole-body fat mass (ALA: 41%, GLY: 49% P < 0.01), and restored glucose tolerance to control values in ALA and GLY groups. GLY treated mice lost more whole-body fat mass (14%, p < 0.05) and epididymal fat mass (26%, P < 0.05), less lean mass (27%, P < 0.05), and had better preserved quadriceps muscle mass (4%, P < 0.01) than ALA treated mice after 20 d CR. Compared to the HFD group, pro-inflammatory genes were lower (P < 0.05), metabolic genes higher (P < 0.05) and S6 protein phosphorylation lower after CR, but not different between ALA and GLY groups. There were significant correlations between %initial fat mass (pre CR) and the mRNA expression of genes involved in inflammation (r = 0.51 to 0.68, P < 0.05), protein breakdown (r = -0.66 to -0.37, P < 0.05) and metabolism (r = -0.59 to -0.47, P < 0.05) after CR. Taken together, these findings suggest that glycine supplementation during CR may be beneficial for preserving muscle mass and stimulating loss of adipose tissue. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  6. Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice.

    PubMed

    Devlin, M J; Brooks, D J; Conlon, C; Vliet, M van; Louis, L; Rosen, C J; Bouxsein, M L

    2016-06-01

    Starvation induces low bone mass and high bone marrow adiposity in humans, but the underlying mechanisms are poorly understood. The adipokine leptin falls in starvation, suggesting that hypoleptinemia may be a link between negative energy balance, bone marrow fat accumulation, and impaired skeletal acquisition. In that case, treating mice with leptin during caloric restriction (CR) should reduce marrow adipose tissue (MAT) and improve bone mass. To test this hypothesis, female C57Bl/6J mice were fed a 30% CR or normal (N) diet from 5 to 10 weeks of age, with daily injections of vehicle (VEH), 1mg/kg leptin (LEP1), or 2mg/kg leptin (LEP2) (N=6-8/group). Outcomes included body mass, body fat percentage, and whole-body bone mineral density (BMD) via peripheral dual-energy X-ray absorptiometry, cortical and trabecular microarchitecture via microcomputed tomography (μCT), and MAT volume via μCT of osmium tetroxide-stained bones. Overall, CR mice had lower body mass, body fat percentage, BMD, and cortical bone area fraction, but more connected trabeculae, vs N mice (P<0.05 for all). Most significantly, although MAT was elevated in CR vs N overall, leptin treatment blunted MAT formation in CR mice by 50% vs VEH (P<0.05 for both leptin doses). CR LEP2 mice weighed less vs CR VEH mice at 9-10 weeks of age (P<0.05), but leptin treatment did not affect body fat percentage, BMD, or bone microarchitecture within either diet. These data demonstrate that once daily leptin bolus during CR inhibits bone marrow adipose expansion without affecting bone mass acquisition, suggesting that leptin has distinct effects on starvation-induced bone marrow fat formation and skeletal acquisition. © 2016 Society for Endocrinology.

  7. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    PubMed Central

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  8. A Comparative Genotoxicity Study of a Supraphysiological Dose of Triiodothyronine (T3) in Obese Rats Subjected to Either Calorie-Restricted Diet or Hyperthyroidism

    PubMed Central

    De Sibio, Maria Teresa; Luvizotto, Renata Azevedo Melo; Olimpio, Regiane Marques Castro; Corrêa, Camila Renata; Marino, Juliana; de Oliveira, Miriane; Conde, Sandro José; Ferreira, Ana Lúcia dos Anjos; Padovani, Carlos Roberto; Nogueira, Célia Regina

    2013-01-01

    This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. PMID:23468891

  9. Calorie restriction delays the progression of lesions to pancreatic cancer in the LSL-KrasG12D; Pdx-1/Cre mouse model of pancreatic cancer.

    PubMed

    Lanza-Jacoby, Susan; Yan, Guang; Radice, Glenn; LePhong, Christopher; Baliff, Jeffrey; Hess, Rachael

    2013-07-01

    Since pancreatic cancer is a lethal disease, developing prevention strategies is an important goal. We determined whether calorie restriction would prevent the development and delay progression of pancreatic intraepithelial neoplasms to pancreatic ductal adenocarcinoma (PDA) in LSL-KrasG12D/+; Pdx-1/Cre mice that develop all the precursor lesions that progress to PDA. Eight-week-old LSL-KrasG12D; Pdx-1/Cre mice were assigned to three groups: (1) ad libitum (AL) fed the AIN93M diet or (2) intermittently calorie restricted (ICR) a modified AIN93M at 50% of AL intake followed by one week intervals at 100% of AL intake, or (3) chronically calorie restricted (CCR) an AIN93M diet at 75% of AL intake. AL fed mice had a greater percentage of pancreatic ducts with PanIN-2 (13.6%) than did the ICR (1.0%) and CCR groups (1.6%), P < 0.0001. Calorie restriction (ICR [0%] and CCR [0.7%]) reduced the percentage of ducts with PanIN-3 lesions compared to the AL group (7.0%), P < 0.0001. The incidence of PanIN-2 or more lesions was significantly reduced in both ICR (27%; n = 16) and CCR (40%) mice (n = 15; P < 0.001) compared to AL (70%) fed mice (n = 11). The delayed progression of lesions in ICR and CCR mice was associated with reduced proliferation measured by proliferating cell nuclear antigen staining, reduced protein expression of Glut1, increased protein expression of Sirt1, increased serum adiponectin, and decreased serum leptin. CCR resulted in decreased phosphorylated mammalian target of rapamycin and decreased serum insulin-like growth factor-1. In summary, this is the first study to show in LSL-KrasG12D; Pdx-1/Cre mice that ICR and CCR delay the progression of lesions to PDA.

  10. Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane.

    PubMed

    Zanquetta, Melissa M; Seraphim, Patricia M; Sumida, Doris H; Cipolla-Neto, Jose; Machado, Ubiratan F

    2003-10-01

    The present study aimed to investigate insulin sensitivity and GLUT4 expression protein in pinealectomized rats, as well as to determining the effects of melatonin and calorie restriction on the changes induced by pinealectomy. Wistar rats were pinealectomized (Pinx) or sham operated (Sham), and studied 30 days later. Melatonin replacement treatment (50 g/100 g body weight) was continued for 30 days after pinealectomy. Calorie restriction was performed by offering 60% of the standard food intake. In vivo insulin sensitivity was evaluated using the glucose disappearance constant (kITT) during an insulin tolerance test, and GLUT4 mRNA and protein were assessed by Northern and Western blotting, respectively. The in vitro effect of melatonin on GLUT4 protein content in plasma membrane was investigated in adipocytes isolated from intact rats. Compared with Sham rats, Pinx rats showed decreased kITT (40%), GLUT4 expression in white adipose tissue (WAT, approximately 70%), and unchanged GLUT4 expression in skeletal muscle. Melatonin treatment in Pinx rats restored the kITT and GLUT4 protein to control values. No in vitro effects of melatonin (10-9 m) upon GLUT4 protein were observed. Calorie restriction of Pinx rats increased their kITT value ( approximately 40%), total GLUT4 protein content ( approximately 240%) and its translocation to the plasma membrane ( approximately 80%) in WAT. The results show that pinealectomy, for lack of melatonin, decreased insulin sensitivity as well as GLUT4 gene expression. Calorie restriction improved insulin sensitivity in Pinx rats, and this was related to increased GLUT4 gene expression and insulin-induced GLUT4 translocation to the plasma membrane in WAT.

  11. Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study.

    PubMed

    Sridharan, Aadhavi; Pehar, Mariana; Salamat, M Shahriar; Pugh, Thomas D; Bendlin, Barbara B; Willette, Auriel A; Anderson, Rozalyn M; Kemnitz, Joseph W; Colman, Ricki J; Weindruch, Richard H; Puglielli, Luigi; Johnson, Sterling C

    2013-05-01

    While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods. CR monkeys expressed significantly lower levels (∼30% on average) of GFAP than Controls in the CA region of the hippocampus and entorhinal cortex, suggesting a protective effect of CR in limiting astrogliosis. These results recapitulate the neuroprotective effects of CR seen in shorter-lived animal models. There was a significant positive association between age and average amyloid plaque pathology in these animals, but there was no significant difference in amyloid plaque distribution between the two groups. Two of the seven Control animals (28.6%) and one of the six CR animal (16.7%) did not express any amyloid plaques, five of seven Controls (71.4%) and four of six CR animals (66.7%) expressed minimal to moderate amyloid pathology, and one of six CR animals (16.7%) expressed severe amyloid pathology. That CR affects levels of GFAP expression but not amyloid plaque load provides some insight into the means by which CR is beneficial at the microstructural level, potentially by offsetting the increased load of oxidatively damaged proteins, in this non-human primate model of aging. The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms. Published by Elsevier B.V.

  12. Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study

    PubMed Central

    Sridharan, Aadhavi; Pehar, Mariana; Salamat, M Shahriar; Pugh, Thomas D; Bendlin, Barbara B; Willette, Auriel A; Anderson, Rozalyn M; Kemnitz, Joseph W; Colman, Ricki J; Weindruch, Richard H; Puglielli, Luigi; Johnson, Sterling C

    2013-01-01

    While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods. CR monkeys expressed significantly lower levels (∼30% on average) of GFAP than Controls in the CA region of the hippocampus and entorhinal cortex, suggesting a protective effect of CR in limiting astrogliosis. These results recapitulate the neuroprotective effects of CR seen in shorter-lived animal models. There was a significant positive association between age and average amyloid plaque pathology in these animals, but there was no significant difference in amyloid plaque distribution between the two groups. Two of the seven Control animals (28.6%) and one of the six CR animal (16.7%) did not express any amyloid plaques, five of seven Controls (71.4%) and four of six CR animals (66.7%) expressed minimal to moderate amyloid pathology, and one of six CR animals (16.7%) expressed severe amyloid pathology. That CR affects levels of GFAP expression but not amyloid plaque load provides some insight into the means by which CR is beneficial at the microstructural level, potentially by offsetting the increased load of oxidatively damaged proteins, in this non-human primate model of aging. The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms. PMID:23473840

  13. Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

    PubMed Central

    Sharov, Alexei A; Falco, Geppino; Piao, Yulan; Poosala, Suresh; Becker, Kevin G; Zonderman, Alan B; Longo, Dan L; Schlessinger, David; Ko, Minoru SH

    2008-01-01

    Background The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR). Results We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis. Conclusion Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary. PMID:18522719

  14. Effects of calorie restriction on reproductive and adrenal systems in Japanese quail: are responses similar to mammals, particularly primates?

    PubMed

    Ottinger, Mary Ann; Mobarak, Mohammed; Abdelnabi, Mahmoud; Roth, George; Proudman, John; Ingram, Donald K

    2005-09-01

    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.

  15. Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity

    PubMed Central

    Dutta, Debariya; Xu, Jinze; Dirain, Marvin L.S.; Leeuwenburgh, Christiaan

    2014-01-01

    The multiple beneficial effects of calorie restriction (CR) on several organs, including the heart, are widely known. Recently, the plant polyphenol resveratrol has been shown to possess beneficial effects similar to that of CR. Among the host of effects on cardiac muscle, a cellular self-eating process called autophagy has been shown to be induced by both CR and resveratrol. Autophagy is vital in removing dysfunctional organelles and damaged proteins from the cell, thereby maintaining cellular quality control. In this study, we explored whether short-term moderate CR (20%), either alone or in combination with resveratrol, can induce autophagy in the hearts of 26-month old Fischer 344 × Brown Norway (FBN) rats. Autophagy stimulation was investigated by measuring protein expression levels of autophagy proteins Beclin-1, Atg5, p62, and LC3-II/LC3-I ratio. We found that 20% CR or resveratrol alone for 6 weeks could not induce autophagy, but 20% CR in combination with 50 mg/kg/day resveratrol resulted in an induction of autophagy in the hearts of 26 month old rats. Although oxidative stress has been proposed to be an inducer of autophagy, treatment with the chemotherapeutic drug doxorubicin was unable to stimulate autophagy. The enhanced autophagy due to CR + resveratrol was associated with protection from doxorubicin-induced damage, as measured by cardiac apoptotic levels, serum creatine kinase (CK) and lactate dehydrogenase (LDH) activity. We propose that a combinatorial approach of low-dose CR and resveratrol has the potential to be used therapeutically to induce autophagy and provides protection against doxorubicin-mediated toxicity. PMID:24975655

  16. Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction.

    PubMed

    López-Domínguez, José Alberto; Cánovas, Ángela; Medrano, Juan F; Islas-Trejo, Alma; Kim, Kyoungmi; Taylor, Sandra L; Villalba, José Manuel; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon J

    2016-05-01

    Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil.

  17. Impact of moderate calorie restriction on testicular morphology and endocrine function in adult rhesus macaques (Macaca mulatta).

    PubMed

    Sitzmann, Brandon D; Brown, Donald I; Garyfallou, Vasilios T; Kohama, Steven G; Mattison, Julie A; Ingram, Donald K; Roth, George S; Ottinger, Mary Ann; Urbanski, Henryk F

    2014-02-01

    We previously reported that moderate calorie restriction (CR) has minimal impact on testicular gene expression in young adult rhesus macaques, and no obvious negative impact on semen quality or plasma testosterone levels. We now extend these findings by examining the influence of CR on various aspects of the reproductive axis of older males, including 24-h circulating testosterone levels, testicular gene expression, and testicular morphology. Young adult and old adult male rhesus macaques were subjected to either 30 % CR for 5-7 years, or were fed a standard control diet. Analysis of the 24-h plasma testosterone profiles revealed a significant age-associated decline, but no evidence for CR-induced suppression in either the young or old males. Similarly, expression profiling of key genes associated with testosterone biosynthesis and Leydig cell maintenance showed no significant CR-induced changes in either the young or old animals. The only evidence for CR-associated negative effects on the testis was detected in the old animals at the histological level; when old CR animals were compared with their age-matched controls, there was a modest decrease in seminiferous tubule diameter and epithelium height, with a concomitant increase in the number of depleted germ cell lines. Reassuringly, data from this study and our previous study suggest that moderate CR does not negatively impact 24-h plasma testosterone profiles or testicular gene expression. Although there appear to be some minor CR-induced effects on testicular morphology in old animals, it is unclear if these would significantly compromise fertility.

  18. Placental glucose and amino acid transport in calorie-restricted wild-type and Glut3 null heterozygous mice.

    PubMed

    Ganguly, Amit; Collis, Laura; Devaskar, Sherin U

    2012-08-01

    Calorie restriction (CR) decreased placenta and fetal weights in wild-type (wt) and glucose transporter (Glut) 3 heterozygous null (glut3(+/-)) mice. Because placental nutrient transport is a primary energy determinant of placentofetal growth, we examined key transport systems. Maternal CR reduced intra- and transplacental glucose and leucine transport but enhanced system A amino acid transport in wt mice. These transport perturbations were accompanied by reduced placental Glut3 and leucine amino acid transporter (LAT) family member 2, no change in Glut1 and LAT family member 1, but increased sodium coupled neutral amino acid transporter (SNAT) and SNAT2 expression. We also noted decreased total and active phosphorylated forms of mammalian target of rapamycin, which is the intracellular nutrient sensor, the downstream total P70S6 kinase, and pS6 ribosomal protein with no change in total and phosphorylated 4E-binding protein 1. To determine the role of placental Glut3 in mediating CR-induced placental transport changes, we next investigated the effect of gestational CR in glut3(+/-) mice. In glut3(+/-) mice, a key role of placental Glut3 in mediating transplacental and intraplacental glucose transport was established. In addition, reduced Glut3 results in a compensatory increase of leucine and system A transplacental transport. On the other hand, diminished Glut3-mediated intraplacental glucose transport reduced leucine transport and mammalian target of rapamycin and preserved LAT and enhancing SNAT. CR in glut3(+/-) mice further reduced transplacental glucose transport and enhanced system A amino acid transport, although the increased leucine transport was lost. In addition, increased Glut3 was seen and preserved Glut1, LAT, and SNAT. These placental changes collectively protect survival of wt and glut3(+/-) fetuses against maternal CR-imposed reduction of macromolecular nutrients.

  19. Placental Glucose and Amino Acid Transport in Calorie-Restricted Wild-Type and Glut3 Null Heterozygous Mice

    PubMed Central

    Ganguly, Amit; Collis, Laura

    2012-01-01

    Calorie restriction (CR) decreased placenta and fetal weights in wild-type (wt) and glucose transporter (Glut) 3 heterozygous null (glut3+/−) mice. Because placental nutrient transport is a primary energy determinant of placentofetal growth, we examined key transport systems. Maternal CR reduced intra- and transplacental glucose and leucine transport but enhanced system A amino acid transport in wt mice. These transport perturbations were accompanied by reduced placental Glut3 and leucine amino acid transporter (LAT) family member 2, no change in Glut1 and LAT family member 1, but increased sodium coupled neutral amino acid transporter (SNAT) and SNAT2 expression. We also noted decreased total and active phosphorylated forms of mammalian target of rapamycin, which is the intracellular nutrient sensor, the downstream total P70S6 kinase, and pS6 ribosomal protein with no change in total and phosphorylated 4E-binding protein 1. To determine the role of placental Glut3 in mediating CR-induced placental transport changes, we next investigated the effect of gestational CR in glut3+/− mice. In glut3+/− mice, a key role of placental Glut3 in mediating transplacental and intraplacental glucose transport was established. In addition, reduced Glut3 results in a compensatory increase of leucine and system A transplacental transport. On the other hand, diminished Glut3-mediated intraplacental glucose transport reduced leucine transport and mammalian target of rapamycin and preserved LAT and enhancing SNAT. CR in glut3+/− mice further reduced transplacental glucose transport and enhanced system A amino acid transport, although the increased leucine transport was lost. In addition, increased Glut3 was seen and preserved Glut1, LAT, and SNAT. These placental changes collectively protect survival of wt and glut3+/− fetuses against maternal CR-imposed reduction of macromolecular nutrients. PMID:22700768

  20. The effects of calorie restriction on operant-responding for alcohol in the alcohol preferring (iP) rat.

    PubMed

    Guccione, Lisa; Paolini, Antonio G; Penman, Jim; Djouma, Elvan

    2012-04-21

    Calorie restriction (CR) is well established in the research literature to have several beneficial effects on health and has also been found to induce anxiolytic effects in the rat. Heightened levels of stress and anxiety are often regarded as key precipitating factors of relapse to substance abuse and alcohol addiction. In this study, the potential implication of a 25% CR diet in altering drug-seeking and relapse like behaviour through its capacity to influence anxiolytic-like behavioural changes was investigated.Anxiety was assessed in all rats with the elevated plus maze (EPM) and open field test prior to being trained to operantly self-administer either 10% ethanol, or water. Differences were found between the groups in the percentage of open arm/total arm duration and open arm/total arm entries in the EPM,demonstrating the anxiolytic effects of CR25%. Both control and CR25% groups showed preference for alcohol vs. water, however, controls responded more for alcohol during the conditioning phase than the CR25% group. Controls exhibited an alcohol deprivation-effect (ADE) post abstinence, and a cue-induced reinstatement of alcohol-seeking post extinction however the CR25% did not. These results demonstrate that the anxiolytic effects of CR25% reduces operant responding for ethanol and inhibits relapse behaviour.Taken collectively, the results of this study suggest that in line with past research a CR25% dietary regime can induce anxiolytic effects in the alcohol preferring (iP) rat. Furthermore, it also reduces the intake of ethanol and inhibits the ADE and cue-induced relapse that is characteristic of addiction in this strain.

  1. Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction

    SciTech Connect

    Chiba, Takuya; Tsuchiya, Tomoshi; Komatsu, Toshimitsu; Mori, Ryoichi; Hayashi, Hiroko; Shimano, Hitoshi; Spindler, Stephen R.; Shimokawa, Isao

    2010-10-15

    Research highlights: {yields} We identified four sequence motifs lying upstream of putative pro-longevity genes. {yields} One of these motifs binds to HNF-4{alpha}. {yields} HNF-4{alpha}/PGC-1{alpha} could up-regulate the transcription of a reporter gene linked to this motif. {yields} The reporter system described here could be used to screen candidate anti-aging molecules. -- Abstract: Suppression of the growth hormone/insulin-like growth factor-I pathway in Ames dwarf (DF) mice, and caloric restriction (CR) in normal mice extends lifespan and delays the onset of age-related disorders. In combination, these interventions have an additive effect on lifespan in Ames DF mice. Therefore, common signaling pathways regulated by DF and CR could have additive effects on longevity. In this study, we tried to identity the signaling mechanism and develop a system to assess pro-longevity status in cells and mice. We previously identified genes up-regulated in the liver of DF and CR mice by DNA microarray analysis. Motif analysis of the upstream sequences of those genes revealed four major consensus sequence motifs, which have been named dwarfism and calorie restriction-responsive elements (DFCR-REs). One of the synthesized sequences bound to hepatocyte nuclear factor-4{alpha} (HNF-4{alpha}), an important transcription factor involved in liver metabolism. Furthermore, using this sequence information, we developed a highly sensitive bioassay to identify chemicals mimicking the anti-aging effects of CR. When the reporter construct, containing an element upstream of a secreted alkaline phosphatase (SEAP) gene, was co-transfected with HNF-4{alpha} and its regulator peroxisome proliferator-activated receptor (PPAR) {gamma} coactivator-1{alpha} (PGC-1{alpha}), SEAP activity was increased compared with untransfected controls. Moreover, transient transgenic mice established using this construct showed increased SEAP activity in CR mice compared with ad libitum-fed mice. These data

  2. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    PubMed Central

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  3. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

    PubMed Central

    2012-01-01

    Background Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR). Methods Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. Results In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice. Conclusions CR exerts

  4. Hypothalamic Npy mRNA is correlated with increased wheel running and decreased body fat in calorie-restricted rats.

    PubMed

    Ruegsegger, Gregory N; Speichinger, Katherine R; Manier, Jacob B; Younger, Kyle M; Childs, Thomas E; Booth, Frank W

    2016-04-08

    The neuro-molecular mechanisms that regulate the relationship between physical activity level, energy homeostasis regulation, and body fat are unclear. Thus, we aimed to investigate the relationship between mRNAs in the hypothalamic arcuate nucleus (ARC) related to energy homeostasis, wheel running distance, and body fat in ad lib (AL) and calorie-restricted (CR) growing rats. We hypothesized that changes in select mRNAs (Pomc, Cart, Agrp, Npy, Lepr, Insr, Mc4r, Ampk, Sirt1, Sirt3) in CR would be associated with decreases in body fat percentage and increased wheel running behavior. Male Wistar rats were given access to voluntary running wheels at 4 weeks of age and randomized into AL (n=8) and CR (70% of AL; n=7) groups at 5 weeks of age until study termination at 12 weeks of age. Body composition, serum leptin, insulin, and adiponectin, and ARC mRNA expression in AL and CR rats were assessed and correlated with week-12 running distance to examine potential relationships that may exist. By 12 weeks of age, wheel running was increased ∼3.3-fold (p=0.03) while body fat percentage was ∼2-fold lower in CR compared to AL (p=0.001). Compared to AL, ARC Npy mRNA expression was ∼2-fold greater in CR (p=0.02), while Lepr, Insr, Ampk, and Sirt1 mRNA were additionally increased in CR (p<0.05). Significant correlations existed between ARC Npy mRNA levels versus week-12 wheel running distance (r=0.81, p=0.03), body fat (r=-0.93, p<0.01), and between body fat and wheel running (r=-0.83, p=0.02) in CR, but not in AL. These results reveal possible mechanisms by which fat-brain crosstalk may influence physical activity during energy deficit. These data suggest that below a 'threshold' fat content, body fat may drive activity levels, potentially through hypothalamic Npy action. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Calorie restriction increases lipopolysaccharide-induced neuropeptide Y immunolabeling and reduces microglial cell area in the arcuate hypothalamic nucleus.

    PubMed

    Radler, M E; Wright, B J; Walker, F R; Hale, M W; Kent, S

    2015-01-29

    Calorie restriction (CR) increases longevity and elicits many health promoting benefits including delaying immunosenescence and reducing the incidence of age-related diseases. Although the mechanisms underlying the health-enhancing effects of CR are not known, a likely contributing factor is alterations in immune system functioning. CR suppresses lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines, blocks LPS-induced fever, and shifts hypothalamic signaling pathways to an anti-inflammatory bias. Furthermore, we have recently shown that CR attenuates LPS-stimulated microglial activation in the hypothalamic arcuate nucleus (ARC), a brain region containing neurons that synthesize neuropeptide Y (NPY), an orexigenic neuropeptide that is upregulated by a CR diet and has anti-inflammatory properties. To determine if increased NPY expression in the ARC following CR was associated with changes in microglial activation, a set of brain sections from mice that were exposed to 50% CR or ad libitum feeding for 28 days before being injected with LPS were immunostained for NPY. The density of NPY-immunolabeling was assessed across the rostrocaudal extent of the ARC and hypothalamic paraventricular nucleus (PVN). An adjacent set of sections were immunostained for ionized calcium-binding adapter molecule-1 (Iba1) and immunostained microglia in the ARC were digitally reconstructed to investigate the effects of CR on microglial morphology. We demonstrated that exposure to CR increased NPY expression in the ARC, but not the PVN. Digital reconstruction of microglia revealed that LPS increased Iba1 intensity in ad libitum fed mice but had no effect on Iba1 intensity in CR mice. CR also decreased the size of ARC microglial cells following LPS. Correlational analyses revealed strong associations between NPY and body temperature, and body temperature and microglia area. Together these results suggest that CR-induced changes in NPY are not directly involved in the

  6. Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects.

    PubMed

    Lips, Mirjam A; Pijl, Hanno; van Klinken, Jan B; de Groot, Gerrit H; Janssen, Ignace M; Van Ramshorst, Bert; Van Wagensveld, Bart A; Swank, Dingeman J; Van Dielen, Fracois; Smit, Johannes W A

    2013-09-01

    Obesity and weight loss influence thyroid hormone physiology. The effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) in obese subjects have not been studied in parallel. We hypothesized that differences in transient systemic inflammation and catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology. We recruited 12 lean and 27 obese females with normal fasting glucose (normal glucose tolerant (NGT)) and 27 obese females with type 2 diabetes mellitus (T2DM) for this study. Weight loss was achieved by restrictive treatment (gastric banding or high-protein-low-calorie diet) or by RYGB. Fasting serum leptin, TSH, triiodothyronine (T₃), reverse T₃ (rT₃), and free thyroxine (fT₄) concentrations were measured at baseline and 3 weeks and 3 months after the start of the interventions. Obesity was associated with higher TSH, T₃, and rT₃ levels and normal fT₄ levels in all the subjects when compared with the controls. After 3 weeks, calorie restriction and RYGB induced a decline in TSH levels and a rise in rT₃ and fT₄ levels. The increase in rT₃ levels correlated with serum interleukin 8 (IL8) and IL6 levels. After 3 months, fT₄ and rT₃ levels returned to baseline levels, whereas TSH and T₃ levels were persistently decreased when compared with baseline levels. No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM subjects were observed at any time point. In summary, weight loss directly influences thyroid hormone regulation, independently of the weight loss strategy used. The effects may be explained by a combination of decreased leptin levels and transient changes in peripheral thyroid hormone metabolism.

  7. Inhibition of Akt2 phosphorylation abolishes the calorie restriction-induced improvement in insulin-stimulated glucose uptake by rat soleus muscle

    PubMed Central

    Sharma, Naveen; Arias, Edward B.; Cartee, Gregory D.

    2017-01-01

    Calorie restriction (CR; ~60–65% of ad libitum, AL, consumption) can enhance insulin-stimulated glucose uptake (ISGU) in predominantly slow-twitch skeletal muscles (e.g., soleus) by an incompletely understood mechanism. We used an Akt inhibitor (MK-2206) to eliminate CR’s effect on insulin-stimulated Akt2 phosphorylation in isolated rat soleus muscles. We found long-term CR-enhanced ISGU was abolished by eliminating the CR-effect on Akt2 phosphorylation, suggesting the CR-induced benefit on ISGU in the predominantly slow-twitch soleus relies on enhanced Akt2 phosphorylation. PMID:27786542

  8. Calorie restriction prevents the occlusive coronary vascular disease of autoimmune (NZW x BXSB)F1 mice.

    PubMed

    Mizutani, H; Engelman, R W; Kinjoh, K; Kurata, Y; Ikehara, S; Matsuzawa, Y; Good, R A

    1994-05-10

    Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease (CVD) with myocardial infarction. To determine whether this murine lupus-associated CVD can be prevented by the reduction of dietary calories, male W/BF1 mice were separated into five experimental groups and fed either ad libitum (designated group A, n = 50), fed 32% fewer calories of an otherwise comparable diet (designated group B6, n = 20), or initially fed ad libitum and then switched to reduced calorie intake (RCI) feeding at ages 14, 17, or 22 weeks (designated B14, n = 10; B17, n = 20; or B22, n = 20). Occlusive CVD was prevented by RCI. Life-span was significantly extended among the early onset RCI cohorts, B6 and B14 (P = 0.0001 and P = 0.005), compared to group A mice. Mean anti-cardiolipin autoantibody titers and mean levels of circulating immune complexes were also lowered in RCI mice when all RCI mice were compared to ad libitum fed group A mice. Histological grades of both coronary vascular and glomerular lesions were significantly less than those of group A mice (P < 0.001). Immunoprecipitates indicative of immunoglobulin deposition within coronary or glomerular vascular walls were also substantially less than those of group A mice. These findings indicate a possible causal role for anti-cardiolipin autoantibody in development of autoimmune CVD in W/BF1 mice and suggest that regulating dietary calories can influence the mechanism involved in pathogenesis of autoimmune-associated CVD development.

  9. Protection against cisplatin in calorie-restricted Saccharomyces cerevisiae is mediated by the nutrient-sensor proteins Ras2, Tor1, or Sch9 through its target glutathione.

    PubMed

    Mariani, Diana; Castro, Frederico A V; Almeida, Luciana G; Fonseca, Fernanda L; Pereira, Marcos D

    2014-12-01

    There is substantial interest in developing alternative strategies for cancer chemotherapy aiming to increase drug specificity and prevent tumor resistance. Calorie restriction (CR) has been shown to render human cancer cells more susceptible to drugs than normal cells. Indeed, deficiency of nutrient signaling proteins mimics CR, which is sufficient to improve oxidative stress response and life expectancy only in healthy cells. Thus, although CR and reduction of nutrient signaling may play an important role in cellular response to chemotherapy, the full underlying mechanisms are still not completely understood. Here, we investigate the relationship between the nutrient sensor proteins Ras2, Sch9, or Tor1 and the response of calorie-restricted Saccharomyces cerevisiae cells to cisplatin. Using wild-type and nutrient-sensing mutant strains, we show that deletion of any of these proteins mimics CR and is sufficient to increase cell protection. Moreover, we show that glutathione (GSH) is essential for proper CR protection of yeast cells under cisplatin chemotherapy. By measuring the survival rates and GSH levels, we found that cisplatin cytotoxicity leads to a decrease in GSH content reflecting in an increase of oxidative damage. Finally, investigating DNA fragmentation and apoptosis, we conclude that GSH contributes to CR-mediated cell survival.

  10. Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans

    PubMed Central

    Bilet, Lena; Houtkooper, Riekelt H.; van de Weijer, Tineke; Goossens, Gijs H.; Hoeks, Joris; van der Krieken, Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Hesselink, Matthijs K.C.; Kunz, Iris; Schrauwen-Hinderling, Vera B.; Blaak, Ellen; Auwerx, Johan; Schrauwen, Patrick

    2013-01-01

    Summary Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. PMID:22055504

  11. Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study.

    PubMed

    Merra, G; Miranda, R; Barrucco, S; Gualtieri, P; Mazza, M; Moriconi, E; Marchetti, M; Chang, T F M; De Lorenzo, A; Di Renzo, L

    2016-07-01

    Obesity plays a relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional and metabolic factors. We conducted a dietary intervention case-control randomized trial, to compare the effectiveness on body composition of two nutritional protocols: a very-low-carbohydrate ketogenic diet (VLCKD), integrated by an aminoacid supplement with whey protein, and very low restricted-calorie diet (VLCD). The clinical study was conducted with a randomized case-control in which twenty-five healthy subjects gave informed consent to participate in the interventional study and were evaluated for their health and nutritional status, by anthropometric, and body composition evaluation. The results of this pilot study show that a diet low in carbohydrates, associated with a decreased caloric intake, is effective in weight loss. After VLCKD, versus VLCD, no significant differences in body lean of the trunk, body lean distribution (android and gynoid), total body lean were observed (p > 0.05). After VLCKD, no increasing of sarcopenia frequency, according ASSMI, was observed. Many studies have shown the effectiveness of the ketogenic diet on weight loss; even if not know how to work effectively, as some researchers believe that the weight loss is due to reduced calorie intake, satiety could also be induced by the effect of the proteins, rather than the low-carbohydrates. Our pilot study showed that a VLCKD was highly effective in terms of body weight reduction without to induce lean body mass loss, preventing the risk of sarcopenia. Further clinical trials are needed on a larger population and long-term body weight maintenance and risk factors management effects of VLCKD. There is no doubt, however, that a proper dietary approach would impact significantly on the reduction of public expenditure costs, in view of prospective data on increasing the percentage of obese people in our nation.

  12. Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat.

    PubMed

    Kim, Jong-Hee; Kwak, Hyo-Bum; Leeuwenburgh, Christiaan; Lawler, John M

    2008-04-01

    Muscle atrophy is a highly prevalent condition among older adults, and results from reduced muscle mass and fiber cross-sectional area. Resistive exercise training and moderate (30-40%) caloric restriction may reduce the rate of sarcopenia in animal models. We tested the hypothesis that lifelong, voluntary exercise combined with mild (8%) caloric restriction would attenuate the reduction of muscle fiber cross-sectional area in the rat plantaris. Fischer-344 rats were divided into: young adults (6 mo) fed ad libitum (YAL); 24 mo old fed ad libitum (OAL); 24 mo old on 8% caloric restriction (OCR); lifelong wheel running with 8% CR (OExCR). Plantaris fiber cross-sectional area was significantly lower in OAL than YAL (-27%), but protected in OCR and OExCR, while mass/body mass ratio was preserved in OExCR only. Furthermore, 8% CR and lifelong wheel running attenuated the age-induced increases in extramyocyte space and connective tissue. Citrate synthase activity decreased with age, but was not significantly protected in OCR and OExCR. Total hydroperoxides were higher in OAL than YAL, but were not elevated in OExCR, with out a change in MnSOD. IGF-1 levels were lower in OAL (-57%) than YAL, but partially protected in the OExCR group (+51%).

  13. Lifelong wheel running exercise and mild caloric restriction attenuate nuclear EndoG in the aging plantaris muscle.

    PubMed

    Kim, Jong-Hee; Lee, Yang; Kwak, Hyo-Bum; Lawler, John M

    2015-09-01

    Apoptosis plays an important role in atrophy and sarcopenia in skeletal muscle. Recent evidence suggests that insufficient heat shock proteins (HSPs) may contribute to apoptosis and muscle wasting. In addition, long-term caloric restriction (CR) and lifelong wheel running exercise (WR) with CR provide significant protection against caspase-dependent apoptosis and sarcopenia. Caspase-independent mediators (endonuclease G: EndoG; apoptosis-inducing factor: AIF) of apoptosis are also linked to muscles wasting with disuse and aging. However, the efficacy of CR and WR with CR to attenuate caspase-independent apoptosis and preserve HSPs in aging skeletal muscle are unknown. Therefore, we tested the hypothesis that CR and WR with CR would ameliorate age-induced elevation of EndoG and AIF while protecting HSP27 and HSP70 levels in the plantaris. Male Fischer-344 rats were divided into 4 groups at 11weeks: ad libitum feeding until 6months (YAL); fed ad libitum until 24months old (OAL); 8%CR to 24months (OCR); WR+8%CR to 24months (OExCR). Nuclear EndoG levels were significantly higher in OAL (+153%) than in YAL, while CR (-38%) and WR with CR (-46%) significantly attenuated age-induced increment in nuclear EndoG. HSP27 (-63%) protein content and phosphorylation at Ser82 (-49%) were significantly lower in OAL than in YAL, while HSP27 protein content was significantly higher in OCR (+136%) and OExCR (+155%) and p-HSP27 (+254%) was significantly higher in OExCR compared with OAL, respectively. In contrast, AIF and HSP70 were unaltered by CR or WR with CR in aging muscle. These data indicate that CR and WR with CR attenuate age-associated upregulation of EndoG translocation in the nucleus, potentially involved with HSP27 signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Lifelong Wheel Running Exercise and Mild Caloric Restriction Attenuate Nuclear EndoG in the Aging Plantaris Muscle

    PubMed Central

    Kim, Jong-Hee; Lee, Yang; Kwak, Hyo-Bum; Lawler, John M.

    2016-01-01

    Apoptosis plays an important role in atrophy and sarcopenia in skeletal muscle. Recent evidence suggests that insufficient heat shock proteins (HSPs) may contribute to apoptosis and muscle wasting. In addition, long-term caloric restriction (CR) and lifelong wheel running exercise (WR) with CR provide significant protection against caspase-dependent apoptosis and sarcopenia. Caspase-independent mediators (endonuclease G: EndoG; apoptosis-inducing factor: AIF) of apoptosis are also linked to muscles wasting with disuse and aging. However, the efficacy of CR and WR with CR to attenuate caspase-independent apoptosis and preserve HSPs in aging skeletal muscle are unknown. Therefore, we tested the hypothesis that CR and WR with CR would ameliorate age-induced elevation of EndoG and AIF while protecting HSP27 and HSP70 levels in the plantaris. Male Fischer-344 rats were divided into 4 groups at 11 weeks: ad libitum feeding until 6 mo. (YAL); fed ad libitum until 24 mo. old (OAL); 8%CR to 24 mo. (OCR); WR + 8%CR to 24 mo. (OExCR). Nuclear EndoG levels were significantly higher in OAL (+153%) than in YAL, while CR (−38%) and WR with CR (−46%) significantly attenuated age-induced increment in nuclear EndoG. HSP27 (−63%) protein content and phosphorylation at Ser82 (−49%) were significantly lower in OAL than in YAL, while HSP27 protein content was significantly higher in OCR (+136%) and OExCR (+155%) and p-HSP27 (+254%) was significantly higher in OExCR compared with OAL, respectively. In contrast, AIF and HSP70 were unaltered by CR or WR with CR in aging muscle. These data indicate that CR and WR with CR attenuate age-associated upregulation of EndoG translocation in the nucleus, potentially involved with HSP27 signaling. PMID:26055450

  15. Phylloquinone and Menaquinone-4 Tissue Distribution at Different Life Stages in Male and Female Sprague–Dawley Rats Fed Different VK Levels Since Weaning or Subjected to a 40% Calorie Restriction since Adulthood

    PubMed Central

    Ferland, Guylaine; Doucet, Isabelle; Mainville, Dominique

    2016-01-01

    Whether through the vitamin K-dependent proteins or the individual K vitamers, vitamin K (VK) is associated with a number of age-related conditions (e.g., osteoporosis, atherosclerosis, insulin resistance, cognitive decline). In light of this, we investigated the influence of lifetime dietary VK exposure on the tissue distribution of phylloquinone (K1) and menaquinone-4 (MK-4) vitamers in 3-, 12- and 22-month-old male and female rats fed different K1 diets since weaning or subjected to a 40% calorie restricted diet (CR) since adulthood. Dietary K1 intakes around the minimal amount required for normal blood coagulation had no significant influence on body weights of both male and female rats at different life stages. Tissue contents of the K vitamers differed according to organs, were generally higher in females than in males, and increased with K1 intake. The MK-4/total VK ratios tended to be increased in old age possibly reflecting an increased physiological demand for MK-4 during aging. Our study also confirmed the greater susceptibility of male rats to low VK containing diet, notably at a younger age. Despite lifelong higher K1 intakes per unit body weight, tissue K1 and MK-4 contents at 20 months were generally lower in CR rats compared to their ad libitum (AL) counterparts. Whether the lower tissue MK-4 content is the result of lower synthesis from K1 or greater tissue utilization remains to be determined. However, the more youthful coagulation profile observed in old CR rats (vs. AL rats) tends to support the notion that CR is associated with greater utilization of the K vitamers to sustain physiological functions. PMID:26959054

  16. Phylloquinone and Menaquinone-4 Tissue Distribution at Different Life Stages in Male and Female Sprague-Dawley Rats Fed Different VK Levels Since Weaning or Subjected to a 40% Calorie Restriction since Adulthood.

    PubMed

    Ferland, Guylaine; Doucet, Isabelle; Mainville, Dominique

    2016-03-04

    Whether through the vitamin K-dependent proteins or the individual K vitamers, vitamin K (VK) is associated with a number of age-related conditions (e.g., osteoporosis, atherosclerosis, insulin resistance, cognitive decline). In light of this, we investigated the influence of lifetime dietary VK exposure on the tissue distribution of phylloquinone (K₁) and menaquinone-4 (MK-4) vitamers in 3-, 12- and 22-month-old male and female rats fed different K₁ diets since weaning or subjected to a 40% calorie restricted diet (CR) since adulthood. Dietary K₁ intakes around the minimal amount required for normal blood coagulation had no significant influence on body weights of both male and female rats at different life stages. Tissue contents of the K vitamers differed according to organs, were generally higher in females than in males, and increased with K₁ intake. The MK-4/total VK ratios tended to be increased in old age possibly reflecting an increased physiological demand for MK-4 during aging. Our study also confirmed the greater susceptibility of male rats to low VK containing diet, notably at a younger age. Despite lifelong higher K₁ intakes per unit body weight, tissue K₁ and MK-4 contents at 20 months were generally lower in CR rats compared to their ad libitum (AL) counterparts. Whether the lower tissue MK-4 content is the result of lower synthesis from K₁ or greater tissue utilization remains to be determined. However, the more youthful coagulation profile observed in old CR rats (vs. AL rats) tends to support the notion that CR is associated with greater utilization of the K vitamers to sustain physiological functions.

  17. Early leptin intervention reverses perturbed energy balance regulating hypothalamic neuropeptides in the pre- and postnatal calorie-restricted female rat offspring.

    PubMed

    Gibson, Leena Caroline; Shin, Bo-Chul; Dai, Yun; Freije, William; Kositamongkol, Sudatip; Cho, John; Devaskar, Sherin U

    2015-06-01

    Pre- and postnatal calorie restriction is associated with postnatal growth restriction, reduced circulating leptin concentrations, and perturbed energy balance. Hypothalamic regulation of energy balance demonstrates enhanced orexigenic (NPY, AgRP) and diminished anorexigenic (POMC, CART) neuropeptide expression (PN21), setting the stage for subsequent development of obesity in female Sprague-Dawley rats. Leptin replenishment during the early postnatal period (PN2-PN8) led to reversal of the hypothalamic orexigenic:anorexigenic neuropeptide ratio at PN21 by reducing only the orexigenic (NPY, AgRP), without affecting the anorexigenic (POMC, CART) neuropeptide expression. This hypothalamic effect was mediated via enhanced leptin receptor (ObRb) signaling that involved increased pSTAT3/STAT3 but reduced PTP1B. This was further confirmed by an increase in body weight at PN21 in response to intracerebroventricular administration of antisense ObRb oligonucleotides (PN2-PN8). The change in the hypothalamic neuropeptide balance in response to leptin administration was associated with increased oxygen consumption, carbon dioxide production, and physical activity, which resulted in increased milk intake (PN14) with no change in body weight. This is in contrast to the reduction in milk intake with no effect on energy expenditure and physical activity observed in controls. We conclude that pre- and postnatal calorie restriction perturbs hypothalamic neuropeptide regulation of energy balance, setting the stage for hyperphagia and reduced energy expenditure, hallmarks of obesity. Leptin in turn reverses this phenotype by increasing hypothalamic ObRb signaling (sensitivity) and affecting only the orexigenic arm of the neuropeptide balance. © 2015 Wiley Periodicals, Inc.

  18. Protein and Calorie Restriction Contribute Additively to Protection from Renal Ischemia Reperfusion Injury Partly via Leptin Reduction in Male Mice123

    PubMed Central

    Robertson, Lauren T; Treviño-Villarreal, J Humberto; Mejia, Pedro; Grondin, Yohann; Harputlugil, Eylul; Hine, Christopher; Vargas, Dorathy; Zheng, Hanqiao; Ozaki, C Keith; Kristal, Bruce S; Simpson, Stephen J; Mitchell, James R

    2015-01-01

    Background: Short-term dietary restriction (DR) without malnutrition preconditions against surgical stress in rodents; however, the nutritional basis and underlying nutrient/energy-sensing pathways remain poorly understood. Objectives: We investigated the relative contribution of protein restriction (PR) vs. calorie restriction (CR) to protection from renal ischemia reperfusion injury (IRI) and changes in organ-autonomous nutrient/energy-sensing pathways and hormones underlying beneficial effects. Methods: Mice were preconditioned on experimental diets lacking total calories (0–50% CR) or protein/essential amino acids (EAAs) vs. complete diets consumed ad libitum (AL) for 1 wk before IRI. Renal outcome was assessed by serum markers and histology and integrated over a 2-dimensional protein/energy landscape by geometric framework analysis. Changes in renal nutrient/energy-sensing signal transduction and systemic hormones leptin and adiponectin were also measured. The genetic requirement for amino acid sensing via general control non-derepressible 2 (GCN2) was tested with knockout vs. control mice. The involvement of the hormone leptin was tested by injection of recombinant protein vs. vehicle during the preconditioning period. Results: CR-mediated protection was dose dependent up to 50% with maximal 2-fold effect sizes. PR benefits were abrogated by EAA re-addition and additive with CR, with maximal benefits at any given amount of CR occurring with a protein-free diet. GCN2 was not required for functional benefits of PR. Activation and repression of nutrient/energy-sensing kinases, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1), respectively, on PR reflected a state of negative energy balance, paralleled by 13% weight loss and an 87% decrease in leptin, independent of calorie intake. Recombinant leptin administration partially abrogated benefits of dietary preconditioning against renal IRI. Conclusions: In male mice, PR

  19. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

    PubMed Central

    2012-01-01

    Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle) mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy) in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. This review evaluates the relationship between the macronutrient composition of calorie restricted diets and weight loss using metabolic indicators. Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP) and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1. PMID:22974011

  20. Blood cell transcriptomic-based early biomarkers of adverse programming effects of gestational calorie restriction and their reversibility by leptin supplementation

    PubMed Central

    Konieczna, Jadwiga; Sánchez, Juana; Palou, Mariona; Picó, Catalina; Palou, Andreu

    2015-01-01

    The challenge of preventing major chronic diseases requires reliable, early biomarkers. Gestational mild undernutrition in rats is enough to program the offspring to develop later pathologies; the intake of leptin, a breastmilk component, during lactation may reverse these programming effects. We used these models to identify, in peripheral blood mononuclear cells (PBMCs), transcriptomic-based early biomarkers of programmed susceptibility to later disorders, and explored their response to neonatal leptin intake. Microarray analysis was performed in PBMCs from the offspring of control and 20% gestational calorie-restricted dams (CR), and CR-rats supplemented with physiological doses of leptin throughout lactation. Notably, leptin supplementation normalised 218 of the 224 mRNA-levels identified in PBMCs associated to undernutrition during pregnancy. These markers may be useful for early identification and subsequent monitoring of individuals who are at risk of later diseases and would specifically benefit from the intake of appropriate amounts of leptin during lactation. PMID:25766068

  1. Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction.

    PubMed

    Esquifino, Ana I; Cano, Pilar; Jiménez-Ortega, Vanesa; Fernández-Mateos, Pilar; Cardinali, Daniel P

    2007-08-01

    Virtually all neuroendocrine and immunological variables investigated in animals and humans display biological periodicity. Circadian rhythmicity is revealed for every hormone in circulation as well as for circulating immune cells, lymphocyte metabolism and transformability, cytokines, receptors, and adhesion molecules. Clock genes, notably the three Period (Per1/Per2/Per3) genes and two Cryptochrome (Cry1/Cry2) genes, are present in immune and endocrine cells and are expressed in a circadian manner in human cells. This review discusses the circadian disruption of hormone release and immune-related mechanisms in several animal models in which circulating cytokines are modified including rat adjuvant arthritis, social isolation in rats and rabbits and alcoholism, the aging process and calorie restriction in rats. In every case the experimental manipulation used perturbed the temporal organization by affecting the shape and amplitude of a rhythm or by modifying the intrinsic oscillatory mechanism itself.

  2. Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression.

    PubMed

    Pirat, Celine; Dacquet, Catherine; Leclerc, Veronique; Hennuyer, Nathalie; Beucher-Gaudin, Monique; Zanirato, Ghislaine; Géant, Anne; Staels, Bart; Ktorza, Alain; Farce, Amaury; Caignard, Daniel-Henri; Berthelot, Pascal; Lebegue, Nicolas

    2017-09-08

    A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC50 = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Leptin intake in suckling rats restores altered T3 levels and markers of adipose tissue sympathetic drive and function caused by gestational calorie restriction.

    PubMed

    Konieczna, J; Palou, M; Sánchez, J; Picó, C; Palou, A

    2015-06-01

    Maternal calorie restriction during gestation in rats has been associated with altered white adipose tissue (WAT) sympathetic innervation and function in offspring. Here, we aimed to investigate whether supplementation with oral leptin (a breast milk component) throughout the lactation period may revert the aforementioned adverse programming effects. Three groups of male and female rats were studied at the postnatal day 25: the offspring of control dams, the offspring of 20% calorie-restricted dams during pregnancy (CR) and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Tyrosine hydroxylase (TH) levels and its immunoreactive area, and mRNA expression levels of lipid metabolism-related genes and of deiodinase iodothyronine type II (Dio2) were determined in WAT. Triiodothyronine (T3) levels were determined in the blood. In CR males, leptin treatment restored the decreased TH levels and its immunoreactive area in WAT, and partially normalized expression levels of genes related to lipolysis and fatty acid oxidation (adipose triglyceride lipase, hormone-sensitive lipase, carnitine palmitoyltransferase 1b and peroxisome proliferator-activated receptor gamma coactivator 1-alpha). Leptin treatment also reverted the decreased T3 plasma levels and WAT lipoprotein lipase mRNA levels occurring in CR males and females, and the decreased Dio2 mRNA levels in CR females. Leptin supplementation throughout the lactation period reverts the malprogrammed effects on WAT structure and function induced by undernutrition during pregnancy. These findings support the relevance of the intake of leptin during lactation, bearing clear characteristics of essential nutrient, and provide a strategy to treat and/or prevent the programmed trend to obesity acquired by inadequate fetal nutrition.

  4. Prolonged Calorie Restriction Downregulates Skeletal Muscle mTORC1 Signaling Independent of Dietary Protein Intake and Associated microRNA Expression

    PubMed Central

    Margolis, Lee M.; Rivas, Donato A.; Berrone, Maria; Ezzyat, Yassine; Young, Andrew J.; McClung, James P.; Fielding, Roger A.; Pasiakos, Stefan M.

    2016-01-01

    Short-term (5–10 days) calorie restriction (CR) downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1), however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR). Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or calorie restricted (CR; 40%) adequate (10%, AIN-93M) or high (32%) protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P < 0.05) in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6, and p70S6K were lower (P < 0.05) in CR vs. AL, and total rpS6 was associated with muscle protein content (r = 0.64, r2 = 0.36). Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein. PMID:27761114

  5. Alternate Day Calorie Restriction Improves Clinical Findings and Reduces Markers of Oxidative Stress and Inflammation in Overweight Adults with Moderate Asthma

    PubMed Central

    Johnson, James B.; Summer, Warren; Cutler, Roy G.; Martin, Bronwen; Hyun, Dong-Hoon; Dixit, Vishwa D.; Pearson, Michelle; Nassar, Matthew; Maudsley, Stuart; Carlson, Olga; John, Sujit; Laub, Donald R.; Mattson, Mark P.

    2007-01-01

    Background Asthma is an increasingly common disorder responsible for considerable morbidity and mortality. Although obesity is a risk factor for asthma and weight loss can improve symptoms, many patients do not adhere to low calorie diets and the impact of dietary restriction on the disease process is unknown. Objective A study was designed to determine if overweight asthma patients would adhere to an alternate day calorie restriction (ADCR) dietary regimen, and to establish the effects of the diet on their symptoms, pulmonary function and markers of oxidative stress and inflammation. Methods Ten subjects with BMI>30 were maintained for 8 weeks on a dietary regimen in which they ate ad libitum every other day, while consuming less than 20% of their normal calorie intake on the intervening days. At baseline, and at designated time points during the 8 week study, asthma control, symptoms and Quality of Life questionnaires (ACQ,ASUI, mini-AQLQ) were assessed and blood was collected for analyses of markers of general health, oxidative stress and inflammation. Peak Expiratory Flow (PEF) was measured daily on awakening. Pre and post bronchodilator spirometry was obtained at baseline and 8 weeks. Results Nine of the subjects adhered to the diet and lost an average of 8% of their initial weight during the study. Their asthma related symptoms, control and QOL improved significantly, and PEF increased significantly, within 2 weeks of diet initiation; these changes persisted for the duration of the study. Spirometery was unaffected by ADCR. Levels of serum β-hydroxybutyrate were increased and levels of leptin were decreased on CR days indicating a shift in energy metabolism towards utilization of fatty acids and confirming compliance with the diet. The improved clinical findings were associated with decreased levels of serum cholesterol and triglycerides, striking reductions in markers of oxidative stress (8-isoprostane, nitrotyrosine, protein carbonyls, and 4-hydroxynonenal

  6. Calorie Counter

    MedlinePlus

    ... Get an estimate of the Calories Burned During Exercise and in daily activities. See if you're at a healthy weight with our BMI Calculator . Use our Target Heart Rate Calculator . to get the most out of your ...

  7. Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

    USDA-ARS?s Scientific Manuscript database

    Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition. We evaluated the effect of a 2-year CR regimen on body composition including the influence of sex and body...

  8. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in non-obese men and women: a randomized clinical trial

    USDA-ARS?s Scientific Manuscript database

    Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anti-cancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and c...

  9. System Model Network for Adipose Tissue Signatures Related to Weight Changes in Response to Calorie Restriction and Subsequent Weight Maintenance

    PubMed Central

    Montastier, Emilie; Villa-Vialaneix, Nathalie; Caspar-Bauguil, Sylvie; Hlavaty, Petr; Tvrzicka, Eva; Gonzalez, Ignacio; Saris, Wim H. M.; Langin, Dominique; Kunesova, Marie; Viguerie, Nathalie

    2015-01-01

    Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial

  10. Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1.

    PubMed

    Nogueira, Leticia M; Lavigne, Jackie A; Chandramouli, Gadisetti V R; Lui, Huaitian; Barrett, J Carl; Hursting, Stephen D

    2012-10-01

    The prevalence of obesity, an established risk and progression factor for breast and many other cancer types, remains very high in the United States and throughout the world. Calorie restriction (CR), a reduced-calorie dietary regimen typically involving a 20-40% reduction in calorie consumption, prevents or reverses obesity, and inhibits mammary and other types of cancer in multiple tumor model systems. Unfortunately, the mechanisms underlying the tumor inhibitory effects of CR are poorly understood, and a better understanding of these mechanisms may lead to new intervention targets and strategies for preventing or controlling cancer. We have previously shown that the anticancer effects of CR are associated with decreased systemic levels of insulin-like growth factor-1 (IGF-1), the primary source of which is liver. We have also reported that CR strongly suppresses tumor development and growth in multiple mammary cancer models. To identify CR-responsive genes and pathways, and to further characterize the role of IGF-1 as a mediator of the anticancer effects of CR, we assessed hepatic and mammary gland gene expression, hormone levels and growth of orthotopically transplanted mammary tumors in control and CR mice with and without exogenous IGF-1. C57BL/6 mice were fed either control AIN-76A diet ad libitum (AL), subjected to 20%, 30%, or 40% CR plus placebo timed-release pellets, or subjected to 30% or 40% CR plus timed-release pellets delivering murine IGF-1 (mIGF-1, 20 μg/day). Compared with AL-fed controls, body weights were decreased 14.3% in the 20% CR group, 18.5% in the 30% CR group, and 38% in the 40% CR group; IGF-1 infusion had no effect on body weight. Hepatic transcriptome analyses indicated that compared with 20% CR, 30% CR significantly modulated more than twice the number of genes and 40% CR more than seven times the number of genes. Many of the genes specific to the 40% CR regimen were hepatic stress-related and/or DNA damage-related genes. Exogenous

  11. Genetic Reduction of Insulin-like Growth Factor-1 Mimics the Anticancer Effects of Calorie Restriction on Cyclooxygenase-2–Driven Pancreatic Neoplasia

    PubMed Central

    Lashinger, Laura M.; Malone, Lauren M.; McArthur, Mark J.; Goldberg, Jason A.; Daniels, Elizabeth A.; Pavone, Amy; Colby, Jennifer K.; Smith, Nicole C.; Perkins, Susan N.; Fischer, Susan M.; Hursting, Stephen D.

    2011-01-01

    Risk of pancreatic cancer, the fourth deadliest cancer in the U.S., is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of insulin-like growth factor (IGF)-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing cyclooxygenase (COX)-2 (BK5.COX-2). These findings in CR mice correlated with reductions in Ki-67-positive cells, vascular luminal size, vascular endothelial growth factor expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1-deficient (LID) mice. The ~65% reduction of serum IGF-1 in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy. PMID:21593196

  12. Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial1234

    PubMed Central

    Nicklas, Barbara J; Wang, Xuewen; You, Tongjian; Lyles, Mary F; Demons, Jamehl; Easter, Linda; Berry, Michael J; Lenchik, Leon; Carr, J Jeffrey

    2009-01-01

    Background: Exercise intensity may affect the selective loss of abdominal adipose tissue. Objective: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. Design: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m2): 25–40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (≈400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45–50% (moderate-intensity) or 70–75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. Results: Average weight loss for the 95 women who completed the study was 12.1 kg (±4.5 kg) and was not significantly different across groups. Maximal oxygen uptake (O2max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (≈25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O2max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. Conclusion: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was

  13. Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents.

    PubMed Central

    Lane, M A; Baer, D J; Rumpler, W V; Weindruch, R; Ingram, D K; Tilmont, E M; Cutler, R G; Roth, G S

    1996-01-01

    Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximately 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents. PMID:8633033

  14. A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys

    PubMed Central

    Kastman, EK; Willette, AA; Coe, CL; Bendlin, BB; Kosmatka, KJ; McLaren, DG; Xu, G; Canu, E; Field, AS; Alexander, AL; Voytko, ML; Beasley, TM; Colman, RJ; Weindruch, R; Johnson, SC

    2010-01-01

    Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24, 13 males, 11 females) and standard diets (n= 17, 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus and temporal cortex. A Diet x Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species. PMID:20534842

  15. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile

    PubMed Central

    Mercken, Evi M.; Crosby, Seth D.; Lamming, Dudley W.; JeBailey, Lellean; Krzysik-Walker, Susan; Villareal, Dennis; Capri, Miriam; Franceschi, Claudio; Zhang, Yongqing; Becker, Kevin; Sabatini, David M.; de Cabo, Rafael; Fontana, Luigi

    2013-01-01

    Summary Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR-induced dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation. Furthermore, our data identifies promising pathways for therapeutic targets to combat age-related diseases and promote health in humans. PMID:23601134

  16. Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR).

    PubMed

    Brzęk, Paweł; Gębczyński, Andrzej K; Książek, Aneta; Konarzewski, Marek

    2016-07-01

    Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR.

  17. Artemisinin mimics calorie restriction to extend yeast lifespan via a dual-phase mode: a conclusion drawn from global transcriptome profiling.

    PubMed

    Wang, DaTing; Wu, Ming; Li, SiMing; Gao, Qian; Zeng, QingPing

    2015-05-01

    Calorie restriction (CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for accelerated energy consumption regardless of insufficient nutrient intake. In reconciling the contradiction of less food supply versus much metabolite dispense, we revealed a CR-based mode of dual-phase responses that encompass a phase of mitochondrial enhancement (ME) and a phase of post-mitochondrial enhancement (PME), which can be distinguished by the expression patterns and activity dynamics of mitochondrial signatures. ME is characterized by global antioxidative activation, and PME is denoted by systemic metabolic modulation. CR-mediated aging-delaying effects are replicated by artesunate, a semi-synthetic derivative of the antimalarial artemisinin that can alkylate heme-containing proteins, suggesting artesunate-heme conjugation functionally resembles nitric oxide-heme interaction. A correlation of artesunate-heme conjugation with cytochrome c oxidase activation has been established from adduct formation and activity alteration. Exogenous hydrogen peroxide also mimics CR to trigger antioxidant responses, affect signaling cascades, and alter respiratory rhythms, implying hydrogen peroxide is engaged in lifespan extension. Conclusively, artesunate mimics CR-triggered nitric oxide and hydrogen peroxide to induce antioxidative networks for scavenging reactive oxygen species and mitigating oxidative stress, thereby directing metabolic conversion from anabolism to catabolism, maintaining essential metabolic functionality, and extending life expectancy in yeast.

  18. The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

    PubMed Central

    Villalba, José Manuel; López-Domínguez, José Alberto; Chen, Yana; Khraiwesh, Husam; González-Reyes, José Antonio; del Río, Lucía Fernández; Gutiérrez-Casado, Elena; del Río, Mercedes; Calvo-Rubio, Miguel; Ariza, Julia; de Cabo, Rafael; López-Lluch, Guillermo; Navas, Plácido; Hagopian, Kevork; Burón, María Isabel; Ramsey, Jon Jay

    2015-01-01

    The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95% of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40% less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H+ leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40% CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging. PMID:25860863

  19. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans

    PubMed Central

    Meydani, Simin N.; Das, Sai K.; Pieper, Carl F.; Lewis, Michael R.; Klein, Sam; Dixit, Vishwa D.; Gupta, Alok K.; Villareal, Dennis T.; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J.; Roberts, Susan B.; Holloszy, John O.; Fontana, Luigi

    2016-01-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID:27410480

  20. The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast.

    PubMed

    Easlon, Erin; Tsang, Felicia; Skinner, Craig; Wang, Chen; Lin, Su-Ju

    2008-04-01

    Recent studies suggest that increased mitochondrial metabolism and the concomitant decrease in NADH levels mediate calorie restriction (CR)-induced life span extension. The mitochondrial inner membrane is impermeable to NAD (nicotinamide adenine dinucleotide, oxidized form) and NADH, and it is unclear how CR relays increased mitochondrial metabolism to multiple cellular pathways that reside in spatially distinct compartments. Here we show that the mitochondrial components of the malate-aspartate NADH shuttle (Mdh1 [malate dehydrogenase] and Aat1 [aspartate amino transferase]) and the glycerol-3-phosphate shuttle (Gut2, glycerol-3-phosphate dehydrogenase) are novel longevity factors in the CR pathway in yeast. Overexpressing Mdh1, Aat1, and Gut2 extend life span and do not synergize with CR. Mdh1 and Aat1 overexpressions require both respiration and the Sir2 family to extend life span. The mdh1Deltaaat1Delta double mutation blocks CR-mediated life span extension and also prevents the characteristic decrease in the NADH levels in the cytosolic/nuclear pool, suggesting that the malate-aspartate shuttle plays a major role in the activation of the downstream targets of CR such as Sir2. Overexpression of the NADH shuttles may also extend life span by increasing the metabolic fitness of the cells. Together, these data suggest that CR may extend life span and ameliorate age-associated metabolic diseases by activating components of the NADH shuttles.

  1. The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice.

    PubMed

    Villalba, José Manuel; López-Domínguez, José Alberto; Chen, Yana; Khraiwesh, Husam; González-Reyes, José Antonio; Del Río, Lucía Fernández; Gutiérrez-Casado, Elena; Del Río, Mercedes; Calvo-Rubio, Miguel; Ariza, Julia; de Cabo, Rafael; López-Lluch, Guillermo; Navas, Plácido; Hagopian, Kevork; Burón, María Isabel; Ramsey, Jon Jay

    2015-10-01

    The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40 % less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H(+) leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40 % CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.

  2. Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction.

    PubMed

    Dhahbi, Joseph M; Spindler, Stephen R; Atamna, Hani; Yamakawa, Amy; Guerrero, Noel; Boffelli, Dario; Mote, Patricia; Martin, David I K

    2013-02-01

    MicroRNAs (miRNAs) function to modulate gene expression, and through this property they regulate a broad spectrum of cellular processes. They can circulate in blood and thereby mediate cell-to-cell communication. Aging involves changes in many cellular processes that are potentially regulated by miRNAs, and some evidence has implicated circulating miRNAs in the aging process. In order to initiate a comprehensive assessment of the role of circulating miRNAs in aging, we have used deep sequencing to characterize circulating miRNAs in the serum of young mice, old mice, and old mice maintained on calorie restriction (CR). Deep sequencing identifies a set of novel miRNAs, and also accurately measures all known miRNAs present in serum. This analysis demonstrates that the levels of many miRNAs circulating in the mouse are increased with age, and that the increases can be antagonized by CR. The genes targeted by this set of age-modulated miRNAs are predicted to regulate biological processes directly relevant to the manifestations of aging including metabolic changes, and the miRNAs themselves have been linked to diseases associated with old age. This finding implicates circulating miRNAs in the aging process, raising questions about their tissues of origin, their cellular targets, and their functional role in metabolic changes that occur with aging.

  3. Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis.

    PubMed

    Hayashi, Hiroko; Yamaza, Haruyoshi; Komatsu, Toshimitsu; Park, Seongjoon; Chiba, Takuya; Higami, Yoshikazu; Nagayasu, Takeshi; Shimokawa, Isao

    2008-09-01

    Calorie restriction (CR) may modulate insulin signaling in response to energy intake through suppression of the growth hormone (GH)-IGF-1 axis. We investigated the glucose-stimulated serum insulin response and subsequent alterations in insulin receptor (IR), Akt, and FoxO1 in the rat liver and quadriceps femoris muscle (QFM). Nine-month-old wild-type (W) male Wistar rats fed ad libitum (AL) or a 30% CR diet initiated at 6 weeks of age and GH-suppressed transgenic (Tg) rats fed AL were killed 15 min after intraperitoneal injection of glucose or saline. In W-AL rats, the serum insulin concentration was elevated by glucose injection. Concomitantly, the phosphorylated (p)-IR and p-Akt levels were increased in both tissues. The active FoxO1 level was decreased in the liver, but not significantly in the QFM. In W-CR and Tg-AL rats, the serum insulin response was lower, and no significant changes were noted for the p-IR, p-Akt, or active FoxO1 levels in the liver. In the QFM, the p-Akt level was increased in W-CR and Tg-AL rats with an insignificant elevation of p-IR levels. The phenotypic similarity of W-CR and Tg-AL rats suggest that CR minimizes activation of insulin signaling in response to energy intake mostly through the GH-IGF-1 axis.

  4. Acute stress response modified by modest inhibition of growth hormone axis: a potential machinery of the anti-aging effect of calorie restriction.

    PubMed

    Komatsu, Toshimitsu; Trindade, Lucas S; Chiba, Takuya; Hayashi, Hiroko; Henmi, Tomoko; Ushiroda, Yoko; Mori, Ryoichi; Shimokawa, Isao

    2011-03-01

    Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.

  5. Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice.

    PubMed

    Calvo-Rubio, Miguel; Burón, M Isabel; López-Lluch, Guillermo; Navas, Plácido; de Cabo, Rafael; Ramsey, Jon J; Villalba, José M; González-Reyes, José A

    2016-06-01

    Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age-related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents.

  6. A screening strategy for the discovery of drugs that reduce C/EBPβ-LIP translation with potential calorie restriction mimetic properties

    PubMed Central

    Zaini, Mohamad A.; Müller, Christine; Ackermann, Tobias; Reinshagen, Jeanette; Kortman, Gertrud; Pless, Ole; Calkhoven, Cornelis F.

    2017-01-01

    An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA. We showed before that suppression of LIP in mice, reflecting reduced mTORC1-signaling at the C/EBPβ level, results in CR-type of metabolic improvements. Hence, we aim to find possibilities to pharmacologically down-regulate LIP in order to induce CR-mimetic effects. We engineered a luciferase-based cellular reporter system that acts as a surrogate for C/EBPβ-mRNA translation, emulating uORF-dependent C/EBPβ-LIP expression under different translational conditions. By using the reporter system in a high-throughput screening (HTS) strategy we identified drugs that reduce LIP. The drug Adefovir Dipivoxil passed all counter assays and increases fatty acid β-oxidation in a hepatoma cell line in a LIP-dependent manner. Therefore, these drugs that suppress translation into LIP potentially exhibit CR-mimetic properties. PMID:28198412

  7. Modulation of oxidative phosphorylation machinery signifies a prime mode of anti-ageing mechanism of calorie restriction in male rat liver mitochondria.

    PubMed

    Dani, Diksha; Shimokawa, Isao; Komatsu, Toshimitsu; Higami, Yoshikazu; Warnken, Uwe; Schokraie, Elham; Schnölzer, Martina; Krause, Frank; Sugawa, Michiru D; Dencher, Norbert A

    2010-06-01

    Mitochondria being the major source and target of reactive oxygen species (ROS) play a crucial role during ageing. We analyzed ageing and calorie restriction (CR)-induced changes in abundance of rat liver mitochondrial proteins to understand key aspects behind the age-retarding mechanism of CR. The combination of blue-native (BN) gel system with fluorescence Difference Gel Electrophoresis (DIGE) facilitated an efficient analysis of soluble and membrane proteins, existing as monomers or multi-protein assemblies. Changes in abundance of specific key subunits of respiratory chain complexes I, IV and V, critical for activity and/or assembly of the complexes were identified. CR lowered complex I assembly and complex IV activity, which is discussed as a molecular mechanism to minimize ROS production at mitochondria. Notably, the antioxidant system was found to be least affected. The GSH:GSSG couple could be depicted as a rapid mean to handle the fluctuations in ROS levels led by reversible metabolic shifts. We evaluated the relative significance of ROS generation against quenching. We also observed parallel and unidirectional changes as effect of ageing and CR, in subunits of ATP synthase, cytochrome P450 and glutathione S-transferase. This is the first report on such 'putatively hormetic' ageing-analogous effects of CR, besides the age-retarding ones.

  8. Caloris Basin

    NASA Image and Video Library

    1999-12-07

    Caloris Basin on Mercury, is one of the largest basins in the solar system, its diameter exceeds 1300 kilometers and is in many ways similar to the great Imbrium basin on the Moon. This image is from NASA Mariner 10 spacecraft which launched in 1974.

  9. Alcohol Calorie Calculator

    MedlinePlus

    ... Alcohol Calorie Calculator Find out the number of beer and hard alcohol calories you are consuming. Simply ... calories) Average Drinks Per Week Monthly Subtotal Calories Beer Regular 12 149 Regular Beer Light 12 110 ...

  10. Calorie restriction down-regulates expression of the iron regulatory hormone hepcidin in normal and D-galactose-induced aging mouse brain.

    PubMed

    Wei, Shougang; Shi, Wenli; Li, Man; Gao, Qian

    2014-02-01

    It has been shown that iron progressively accumulates in the brain with age. Calorie restriction (CR) may allay many of the adverse effects of aging on the brain, yet the underlying mechanisms, in particular in relation to brain iron metabolism, remain unclear. This study aimed to investigate the role of CR in the regulation of cerebral cellular iron homeostasis. C57BL/6 mice were randomly divided into four groups of eight. The control group was fed a conventional diet ad libitum; the CR group received 70% of the calories of the control mouse intake per day; the D-galactose (D-gal) group received subcutaneous injection of D-gal at a dose of 100 mg/kg once daily to produce mouse model of aging; the D-gal plus CR group received both of the two interventions for 14 weeks. The Morris water maze (MWM) was employed to test the cognitive performance of all animals, and the expression of iron regulatory genes, ferroportin and hepcidin, in the cortex and hippocampus were detected by quantitative real-time PCR. Compared to the controls, the D-gal group mice showed significant spatial reference memory deficits in the MWM test, whereas the D-gal-CR group mice exhibited almost normal cognitive function, indicating that CR protects against D-gal-induced learning and memory impairment. Hepcidin mRNA expression was increased in the D-gal group, decreased in the CR group, and was basically unchanged in the D-gal-CR group. There was no statistical difference in the transmembrane iron exporter ferroportin expression between control and any of the experimental groups. The results suggest that the anti-aging effects of CR might partially lie in its capacity to reduce or avoid age-related iron accumulation in the brain through down-regulating expression of brain hepcidin--the key negative regulator for intracellular iron efflux--and that facilitating the balance of brain iron metabolism may be a promising anti-aging measure.

  11. Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in the rhesus monkeys

    PubMed Central

    Yamada, Yosuke; Colman, Ricki J; Kemnitz, Joseph W.; Baum, Scott T.; Anderson, Rozalyn M.; Weindruch, Richard; Schoeller, Dale A.

    2013-01-01

    Background Short-term (<1 year) calorie restriction (CR) has been reported to decrease physical activity and metabolic rate in humans and non-human primate models; however, studies examining the very long-term (>10 year) effect of CR on these parameters are lacking. Objective The objective of this study was to examine metabolic and behavioral adaptations to long-term CR longitudinally in rhesus macaques. Design Eighteen (10 male, 8 female) control (C) and 24 (14 male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old were examined after 13 and 18 years of moderate adult-onset CR. Energy expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory chamber (24hrEE). Physical activity was assessed both by metabolic equivalent (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of movements during 24h were also calculated. Age and fat-free mass were included as covariates. Results Adjusted total and 24hr EE were not different between C and CR. Sleeping metabolic rate was significantly lower, and physical activity level was higher in CR than in C independent from the CR-induced changes in body composition. The duration of physical activity above 1.6 METs was significantly higher in CR than in C, and CR had significantly higher accelerometer activity counts than C. Metabolic cost of movements during 24h were significantly lower in CR than in C. The accelerometer activity counts were significantly decreased after seven years in C animals, but not in CR animals. Conclusions The results suggest that long-term CR decreases basal metabolic rate, but maintains higher physical activity with lower metabolic cost of movements compared with C. PMID:23954367

  12. Identification of the dichotomous role of age-related LCK in calorie restriction revealed by integrative analysis of cDNA microarray and interactome.

    PubMed

    Park, Daeui; Lee, Eun Kyeong; Jang, Eun Jee; Jeong, Hyoung Oh; Kim, Byoung-Chul; Ha, Young Mi; Hong, Seong Eui; Yu, Byung Pal; Chung, Hae Young

    2013-08-01

    Among the many experimental paradigms used for the investigation of aging, the calorie restriction (CR) model has been proven to be the most useful in gerontological research. Exploration of the mechanisms underlying CR has produced a wealth of data. To identify key molecules controlled by aging and CR, we integrated data from 84 mouse and rat cDNA microarrays with a protein-protein interaction network. On the basis of this integrative analysis, we selected three genes that are upregulated in aging but downregulated by CR and two genes that are downregulated in aging but upregulated by CR. One of these key molecules is lymphocyte-specific protein tyrosine kinase (LCK). To further confirm this result on LCK, we performed a series of experiments in vitro and in vivo using kidneys obtained from aged ad libitum-fed and CR rats. Our major significant findings are as follows: (1) identification of LCK as a key molecule using integrative analysis; (2) confirmation that the age-related increase in LCK was modulated by CR and that protein tyrosine kinase activity was decreased using a LCK-specific inhibitor; and (3) upregulation of LCK leads to NF-κB activation in a ONOO(-) generation-dependent manner, which is modulated by CR. These results indicate that LCK could be considered a target attenuated by the anti-aging effects of CR. Integrative analysis of cDNA microarray and interactome data are powerful tools for identifying target molecules that are involved in the aging process and modulated by CR.

  13. Mechanisms for independent and combined effects of calorie restriction and acute exercise on insulin-stimulated glucose uptake by skeletal muscle of old rats.

    PubMed

    Sharma, Naveen; Wang, Haiyan; Arias, Edward B; Castorena, Carlos M; Cartee, Gregory D

    2015-04-01

    Either calorie restriction [CR; consuming 60-65% of ad libitum (AL) intake] or acute exercise can independently improve insulin sensitivity in old age, but their combined effects on muscle insulin signaling and glucose uptake have previously been unknown. Accordingly, we assessed the independent and combined effects of CR (beginning at 14 wk old) and acute exercise (3-4 h postexercise) on insulin signaling and glucose uptake in insulin-stimulated epitrochlearis muscles from 30-mo-old rats. Either CR alone or exercise alone vs. AL sedentary controls induced greater insulin-stimulated glucose uptake. Combined CR and exercise vs. either treatment alone caused an additional increase in insulin-stimulated glucose uptake. Either CR or exercise alone vs. AL sedentary controls increased Akt Ser(473) and Akt Thr(308) phosphorylation. Combined CR and exercise further elevated Akt phosphorylation on both sites. CR alone, but not exercise alone, vs. AL sedentary controls significantly increased Akt substrate of 160 kDa (AS160) Ser(588) and Thr(642) phosphorylation. Combined CR and exercise did not further enhance AS160 phosphorylation. Exercise alone, but not CR alone, modestly increased GLUT4 abundance. Combined CR and exercise did not further elevate GLUT4 content. These results suggest that CR or acute exercise independently increases insulin-stimulated glucose uptake via overlapping (greater Akt phosphorylation) and distinct (greater AS160 phosphorylation for CR, greater GLUT4 for exercise) mechanisms. Our working hypothesis is that greater insulin-stimulated glucose uptake in the combined CR and exercise group vs. CR or exercise alone relies on greater Akt activation, leading to greater phosphorylation of one or more Akt substrates other than AS160.

  14. Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine

    PubMed Central

    Salvatore, Michael F.; Terrebonne, Jennifer; Fields, Victoria; Nodurft, Danielle; Runfalo, Cori; Latimer, Brian; Ingram, Donald K.

    2015-01-01

    Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging. PMID:26610387

  15. Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.

    PubMed

    Briggs, Dana I; Lockie, Sarah H; Wu, Qunli; Lemus, Moyra B; Stark, Romana; Andrews, Zane B

    2013-02-01

    Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

  16. A re-evaluation of life-long severe galactose restriction for the nutrition management of classic galactosemia.

    PubMed

    Van Calcar, Sandra C; Bernstein, Laurie E; Rohr, Frances J; Scaman, Christine H; Yannicelli, Steven; Berry, Gerard T

    2014-07-01

    The galactose-restricted diet is life-saving for infants with classic galactosemia. However, the benefit and extent of dietary galactose restriction required after infancy remain unclear and variation exists in practice. There is a need for evidence-based recommendations to better standardize treatment for this disorder. This paper reviews the association between diet treatment and outcomes in classic galactosemia and evaluates the contribution of food sources of free galactose in the diet. Recommendations include allowing all fruits, vegetables, legumes, soy products that are not fermented, various aged cheeses and foods containing caseinates. Further research directions are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Calorie Restriction and Matched Weight Loss From Exercise: Independent and Additive Effects on Glucoregulation and the Incretin System in Overweight Women and Men.

    PubMed

    Weiss, Edward P; Albert, Stewart G; Reeds, Dominic N; Kress, Kathleen S; Ezekiel, Uthayashanker R; McDaniel, Jennifer L; Patterson, Bruce W; Klein, Samuel; Villareal, Dennis T

    2015-07-01

    It is not known whether calorie restriction (CR) has additive benefits to those from exercise (EX)-induced weight loss. We hypothesized that weight loss from CR and EX (CREX) improves insulin sensitivity more than matched weight loss induced by EX or CR alone and that the incretin system may be involved in adaptations to CR. Sedentary, overweight men and women (n = 52, 45-65 years of age) were randomized to undergo 6-8% weight loss by using CR, EX, or CREX. Glucose, insulin, C-peptide, insulin sensitivity, and incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) were measured during frequently sampled oral glucose tolerance tests (FSOGTTs). Incretin effects on insulin secretion were measured by comparing insulin secretion rates from the FSOGTTs to those from a glycemia-matched glucose infusion. Despite similar weight losses in all groups, insulin sensitivity index values increased twofold more in the CREX group (2.09 ± 0.35 μM/kg/pM × 100) than in the CR (0.89 ± 0.39 μM/kg/pM × 100) and EX (1.04 ± 0.39 μM/kg/pM × 100) groups. Postprandial GLP-1 concentrations decreased only in the CR group (P = 0.04); GIP concentrations decreased in all groups. Incretin effects on insulin secretion were unchanged. CR and EX have additive beneficial effects on glucoregulation. Furthermore, the adaptations to CR may involve reductions in postprandial GLP-1 concentrations. These findings underscore the importance of promoting both CR and EX for optimal health. However, because data from participants who withdrew from the study and from those who did not adhere to the intervention were excluded, the results may be limited to individuals who are capable of adhering to a healthy lifestyle intervention. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  18. Effects of Calorie Restriction and Diet-Induced Obesity on Murine Colon Carcinogenesis, Growth and Inflammatory Factors, and MicroRNA Expression

    PubMed Central

    Olivo-Marston, Susan E.; Hursting, Stephen D.; Perkins, Susan N.; Schetter, Aaron; Khan, Mohammed; Croce, Carlo; Harris, Curtis C.; Lavigne, Jackie

    2014-01-01

    Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse azoxymethane (AOM) model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group) after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), adipokines, proliferation, apoptosis, and expression of microRNAs (miRs) were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat), while CR induced a lean phenotype (∼14% body fat); controls were intermediate (∼26% body fat). Relative to controls, DIO increased (and CR decreased) the number of colon tumors (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation (p<0.001). DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs. PMID:24732966

  19. Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats.

    PubMed

    Sharma, Naveen; Arias, Edward B; Bhat, Abhijit D; Sequea, Donel A; Ho, Steve; Croff, Kelsey K; Sajan, Mini P; Farese, Robert V; Cartee, Gregory D

    2011-06-01

    Calorie restriction [CR; ~65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[(3)H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr(308) and Ser(473)) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser(588) and Thr(642)) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses.

  20. Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2014-01-01

    Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. - Highlights: • Utilized a graded CR model in male mice • The mRNA profiles of xenobiotic processing genes (XPGs) in liver were investigated. • CR up-regulates many phase-II enzymes. • CR tends to feminize the mRNA profiles of XPGs.

  1. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

    PubMed

    Olivo-Marston, Susan E; Hursting, Stephen D; Perkins, Susan N; Schetter, Aaron; Khan, Mohammed; Croce, Carlo; Harris, Curtis C; Lavigne, Jackie

    2014-01-01

    Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse azoxymethane (AOM) model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group) after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), adipokines, proliferation, apoptosis, and expression of microRNAs (miRs) were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat), while CR induced a lean phenotype (∼14% body fat); controls were intermediate (∼26% body fat). Relative to controls, DIO increased (and CR decreased) the number of colon tumors (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation (p<0.001). DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs.

  2. Roux-en-Y gastric bypass versus calorie restriction: support for surgery per se as the direct contributor to altered responses of insulin and incretins to a mixed meal.

    PubMed

    Berggren, Johan; Lindqvist, Andreas; Hedenbro, Jan; Groop, Leif; Wierup, Nils

    2017-02-01

    To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR). University-affiliated bariatric surgery clinic. RYGB induces remission of type 2 diabetes (T2D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2D is unknown. Nine normoglycemic patients and 10 T2D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on a very low calorie diet regimen (MMT-1 d), on the morning of the first day after surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. CR lowered insulin in T2D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB. RYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  3. Research Advances: Calorie Restriction and Increased Longevity Linked to Metabolic Changes; Isotope Ratios Reveal Trickery in the Produce Aisle; An Ancient Inca Tax and Metallurgy in Peru

    ERIC Educational Resources Information Center

    King, Angela G.

    2007-01-01

    The different lifelong patterns related to different levels of energy metabolism and the activities of the microbes in various animals are described. The analysis shows that many important beneficial changes occur due to the activities of symbiotic bacteria living in the intestinal tract.

  4. Research Advances: Calorie Restriction and Increased Longevity Linked to Metabolic Changes; Isotope Ratios Reveal Trickery in the Produce Aisle; An Ancient Inca Tax and Metallurgy in Peru

    ERIC Educational Resources Information Center

    King, Angela G.

    2007-01-01

    The different lifelong patterns related to different levels of energy metabolism and the activities of the microbes in various animals are described. The analysis shows that many important beneficial changes occur due to the activities of symbiotic bacteria living in the intestinal tract.

  5. Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes.

    PubMed

    Steven, S; Hollingsworth, K G; Small, P K; Woodcock, S A; Pucci, A; Aribasala, B; Al-Mrabeh, A; Batterham, R L; Taylor, R

    2016-12-01

    To compare directly the impact of glucagon-like peptide-1 secretion on glucose metabolism in individuals with Type 2 diabetes listed for Roux-en-Y gastric bypass surgery, randomized to be studied before and 7 days after undergoing Roux-en-Y gastric bypass or after following a very-low-calorie diet. A semi-solid meal test was used to investigate glucose, insulin and glucagon-like peptide-1 response. Insulin secretion in response to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using magnetic resonance imaging. The decrease in fat mass was almost identical in the Roux-en-Y gastric bypass and the very-low-calorie diet groups (3.0±0.3 and 3.0±0.7kg). The early rise in plasma glucose level and in acute insulin secretion were greater after Roux-en-Y gastric bypass than after a very-low-calorie diet; however, the early rise in glucagon-like peptide-1 was disproportionately greater (sevenfold) after Roux-en-Y gastric bypass than after a very-low-calorie diet. This did not translate into a greater improvement in fasting glucose level or area under the curve for glucose. The reduction in liver fat was greater after Roux-en-Y gastric bypass (29.8±3.7 vs 18.6±4.0%) and the relationships between weight loss and reduction in liver fat differed between the Roux-en-Y gastric bypass group and the very-low-calorie diet group. This study shows that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise in insulin level; however, there was no association with the large post-meal rise in glucagon-like peptide-1, and post-meal glucose homeostasis was similar in the Roux-en-Y gastric bypass and very-low-calorie diet groups. (Clinical trials registry number: ISRCTN11969319.). © 2016 Diabetes UK.

  6. Caloric Restriction

    PubMed Central

    Bales, Connie W.; Kraus, William E.

    2013-01-01

    PURPOSE While the impact of caloric restriction on human health is not fully understood, there is strong evidence to support further studies of its influence on cardiovascular health. The purpose of this review is to update the state of the science by examining the relevant literature regarding calorie restriction effects on aging and cardiovascular health and to discuss the possible role(s) of calorie restriction in preserving cardiovascular function in humans. METHODS For purpose of this review, we have defined calorie restriction as a reduction in energy intake well below the amount of calories that would be consumed ad libitum (≥ 10% in humans, ≥20% in animals). We examined the relevant literature on calorie restriction effects on longevity and cardiovascular health, with an emphasis on the state of the science regarding calorie restriction in humans. We have emphasized the importance of the preliminary and expected findings from the Comprehensive Assessment of the Long-term Effect of Reducing Intake of Energy (CALERIE) trial. RESULTS Evidence from animal studies and a limited number of human trials indicates that calorie restriction has the potential to both delay cardiac aging and help prevent atherosclerotic cardiovascular disease via beneficial effects on blood pressure, lipids, inflammatory processes, and potentially other mechanisms. CONCLUSIONS Based upon its known benefits to cardiometabolic health, including modest calorie restriction in a combined lifestyle program is likely to improve heart health and prevent subsequent cardiovascular events in overweight and obese individuals. Additional study is needed to further illuminate its long-term applicability for older adults and for those with significant comorbidities such as heart failure. PMID:23748374

  7. Burning Questions about Calories.

    ERIC Educational Resources Information Center

    Keller, J. David; Berry, Kimberly A.

    2001-01-01

    Uses questioning techniques to teach about caloric consumption and weight gain. Starts with defining questions about calories and includes the stages of measuring calories, analyzing data, and conducting inquiry research. Includes directions for the experiment. (YDS)

  8. Lifelong Learning

    ERIC Educational Resources Information Center

    Berry, Mary F.

    1977-01-01

    The Lifelong Learning Project (established under the U.S. Department of Health, Education, and Welfare) and possible approaches toward the development of effective and efficient Federal-State relationships in carrying out adult learning programs in communities are discussed along with other implications of the project. (TA)

  9. Lifelong Readers.

    ERIC Educational Resources Information Center

    Sorba, Barbara

    A brief review of the literature on the various approaches which have been used to help children formulate their emerging attitudes towards reading and literature helps clarify the goal of creating lifelong readers. Samway (1991), discussing literature study circles, relates that students read the book they have selected, answer assigned…

  10. Atypical hematological response to combined calorie restriction and chronic hypoxia in Biosphere 2 crew: a possible link to latent features of hibernation capacity.

    PubMed

    Paglia, Donald E; Walford, Roy L

    2005-01-01

    Eight humans were isolated for 2 years in Biosphere 2, a sealed airtight habitat with recycled air, food, water, and wastes. A combination of conditions led to selective decline of oxygen (O2) in the internal atmosphere from 21% to 14%, inducing symptoms of high-altitude sickness but with little or no compensatory increase in red cell production. All crew members exhibited significant decreases in both erythrocyte 2,3-bisphosphoglycerate (2,3-BPG) concentrations and P50 [partial pressure of O2 for 50% hemoglobin (Hb) saturation] values, changes opposite those expected in adaptation to high-altitude hypoxia. Lower P50 with increased Hb-O2 affinity induced by low 2,3-BPG is a characteristic of hibernating species and could be advantageous in O2-impoverished environments. The mechanisms underlying these changes in the Biosphere 2 crew remain obscure but could be related to low-calorie diet (1750-2100 kcal/day). Because the combination of hypoxia and limited caloric intake is also characteristic of hibernation, this unusual response may represent a cross-adaptation phenomenon in which certain features of hibernation capability are expressed in humans.

  11. Differential effects of calorie restriction and involuntary wheel running on body composition and bone structure in diet-induced obese rats

    USDA-ARS?s Scientific Manuscript database

    Weight reduction is recommended to reduce obesity-related health disorders. This study investigated the differential effects of weight reduction through caloric restriction and/or physical activity on bone structure and molecular characteristics of bone metabolism in an obese rat model. We tested th...

  12. Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes.

    PubMed

    Lips, Mirjam A; Van Klinken, Jan B; van Harmelen, Vanessa; Dharuri, Harish K; 't Hoen, Peter A C; Laros, Jeroen F J; van Ommen, Gert-Jan; Janssen, Ignace M; Van Ramshorst, Bert; Van Wagensveld, Bart A; Swank, Dingeman J; Van Dielen, Francois; Dane, Adrie; Harms, Amy; Vreeken, Rob; Hankemeier, Thomas; Smit, Johannes W A; Pijl, Hanno; Willems van Dijk, Ko

    2014-12-01

    Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels. We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention. BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced. Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Perceptions of university students regarding calories, food healthiness, and the importance of calorie information in menu labelling.

    PubMed

    Fernandes, Ana Carolina; de Oliveira, Renata Carvalho; Rodrigues, Vanessa Mello; Fiates, Giovanna Medeiros Rataichesck; da Costa Proença, Rossana Pacheco

    2015-08-01

    This study investigated Brazilian university students' perceptions of the concept of calories, how it relates to food healthiness, and the role of calorie information on menus in influencing food choices in different restaurant settings. Focus groups were conducted with 21 undergraduate students from various universities. Transcriptions were analysed for qualitative content, by coding and grouping words and phrases into similar themes. Two categories were obtained: Calorie concept and connection to healthiness; and Calorie information and food choices in restaurants. Calories were understood as energy units, and their excessive intake was associated with weight gain or fat gain. However, food healthiness was not associated to calorie content, but rather to food composition as a whole. Calorie information on restaurant menus was not considered enough to influence food choices, with preferences, dietary restrictions, food composition, and even restaurant type mentioned as equally or more important. Only a few participants mentioned using calorie information on menus to control food intake or body weight. Students' discussions were suggestive of an understanding of healthy eating as a more complex issue than calorie-counting. Discussions also suggested the need for more nutrition information, besides calorie content, to influence food choices in restaurants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Differential expression of hypothalamic, metabolic and inflammatory genes in response to short-term calorie restriction in juvenile obese- and lean-prone JCR rats

    PubMed Central

    Diane, A; Pierce, W D; Mangat, R; Borthwick, F; Nelson, R; Russell, J C; Heth, C D; Jacobs, R L; Vine, D F; Proctor, S D

    2015-01-01

    Background: Childhood obesity is an important early predictor of adult obesity and associated comorbidities. Common forms of obesity are underpinned by both environmental and genetic factors. However, the rising prevalence of obesity in genetically stable populations strongly suggests that contemporary lifestyle is a premier factor to the disease. In pediatric population, the current treatment/prevention options for obesity are lifestyle interventions such as caloric restriction (CR) and increase physical activity. In obese individuals, CR improves many metabolic parameters in peripheral tissues. Little is known about the effect of CR on the hypothalamus. This study aimed to assess the effect of CR on hypothalamic metabolic gene expression of young obese- and lean-prone animals. Methods: Male juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese-FR rats. Results: In free-feeding conditions, obese-prone rats consumed more energy than lean-prone rats (P<0.001) and showed greater increases in body weight, fat mass, plasma glucose, insulin and lipids (P<0.01). These metabolic differences were associated with alterations of feeding-related neuropeptides expression in the hypothalamus, as well as pro-inflammatory cytokines and oxidative stress markers. When submitted to the same degree of CR, the two genotypes responded differently; hypothalamic inflammatory and oxidative stress gene expression was improved in Obese-FR, while it was worsened in Lean-FR rats. Conclusions: We demonstrate in JCR rats that the metabolic and inflammatory response of the brain to CR is genotype dependent. PMID:26302065

  15. Differential expression of hypothalamic, metabolic and inflammatory genes in response to short-term calorie restriction in juvenile obese- and lean-prone JCR rats.

    PubMed

    Diane, A; Pierce, W D; Mangat, R; Borthwick, F; Nelson, R; Russell, J C; Heth, C D; Jacobs, R L; Vine, D F; Proctor, S D

    2015-08-24

    Childhood obesity is an important early predictor of adult obesity and associated comorbidities. Common forms of obesity are underpinned by both environmental and genetic factors. However, the rising prevalence of obesity in genetically stable populations strongly suggests that contemporary lifestyle is a premier factor to the disease. In pediatric population, the current treatment/prevention options for obesity are lifestyle interventions such as caloric restriction (CR) and increase physical activity. In obese individuals, CR improves many metabolic parameters in peripheral tissues. Little is known about the effect of CR on the hypothalamus. This study aimed to assess the effect of CR on hypothalamic metabolic gene expression of young obese- and lean-prone animals. Male juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese-FR rats. In free-feeding conditions, obese-prone rats consumed more energy than lean-prone rats (P<0.001) and showed greater increases in body weight, fat mass, plasma glucose, insulin and lipids (P<0.01). These metabolic differences were associated with alterations of feeding-related neuropeptides expression in the hypothalamus, as well as pro-inflammatory cytokines and oxidative stress markers. When submitted to the same degree of CR, the two genotypes responded differently; hypothalamic inflammatory and oxidative stress gene expression was improved in Obese-FR, while it was worsened in Lean-FR rats. We demonstrate in JCR rats that the metabolic and inflammatory response of the brain to CR is genotype dependent.

  16. Meal replacements and fibre supplement as a strategy for weight loss. Proprietary PGX® meal replacement and PGX® fibre supplement in addition to a calorie-restricted diet to achieve weight loss in a clinical setting.

    PubMed

    Reichert, Ronald G; Reimer, Raylene A; Kacinik, Veronica; Pal, Sebely; Gahler, Roland J; Wood, Simon

    2013-01-01

    Meal replacements and viscous soluble fibre represent safe and sustainable aids for weight loss. Our purpose was to determine if PGX® meal replacements and PGX(®) fibre complex in combination with a calorie-restricted diet would aid in weight loss in a clinical setting. Fifty-two overweight and obese participants (49 women, 3 men; average age 47.1 years) with a mean body mass index (BMI) of 33.8 ± 6.4 kg/m(2) consumed 57 g of proprietary PGX® meal replacement product at breakfast and another 57 g at lunch for 12 weeks. In addition to the meal replacements, they were also asked to consume 5 g/day of PGX® fibre in the form of granules, powder or capsules together with 250 mlwater. A registered dietician recommended low-fat, low-glycaemic-index foods for snacks and the dinner menus such that each volunteer was consuming a total of 1200 kcal/day. All participants (n = 52) lost a significant amount of weight from baseline (-4.69 ± 3.73 kg), which was further reflected in the reductions in their waist (-7.11 ± 6.35 cm) and hip circumference (-5.59 ± 3.58 cm) over the 12-week study (p < 0.0001). BMI scores (n = 51) were reduced by 1.6 ± 1.4 kg/m(2). The use of PGX® meal replacements and PGX(®) fibre along with a controlled dietary caloric intake is of benefit for short-term weight loss.

  17. Reduced signaling of PI3K-Akt and RAS-MAPK pathways are the key targets for weight loss-induced cancer prevention by dietary calorie restriction and/or physical activity

    PubMed Central

    Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

    2014-01-01

    Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics, and lipidomics were employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into 4 groups for 10 weeks: ad lib-fed sedentary control, ad lib-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE), and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics, and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67, and 110 genes were significantly changed in DCR, PE, and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including upregulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears the reduction of both Ras-MAPK and PI3K-Akt signaling pathways are cancer preventive targets that have been consistently demonstrated by three bioinformatics approaches. PMID:25283328

  18. Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity.

    PubMed

    Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

    2014-12-01

    Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics and lipidomics was employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into four groups for 10 weeks: ad-libitum-fed sedentary control, ad-libitum-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE) and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67 and 110 genes were significantly changed in DCR, PE and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including up-regulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears that the reduction of both Ras-MAPK and PI3K-Akt signaling pathways is a cancer preventive target that has been consistently demonstrated by three bioinformatics approaches.

  19. The Lifelong Learner.

    ERIC Educational Resources Information Center

    Gross, Ronald

    Designed to provide a general guide and stimuli for lifelong learning, this book examines all the positive factors of independent study. Lifelong learning is defined as self-directed growth free from the traditional schooling procedures. Chapters discuss the following: the lifelong learner; profiles of such learners in action; how to be…

  20. Integrating Lifelong Learning Perspectives.

    ERIC Educational Resources Information Center

    Medel-Anonuevo, Carolyn, Ed.

    This publication is comprised of 43 papers on the topic of promoting lifelong learning. The papers in Part 1, Overcoming False Dichotomies, are "Lifelong Learning in the North, Education for All in the South" (Torres); "Practice of Lifelong Learning in Indigenous Africa" (Omolewa); "Gender and Information Societies"…

  1. The Lifelong Learner.

    ERIC Educational Resources Information Center

    Gross, Ronald

    Designed to provide a general guide and stimuli for lifelong learning, this book examines all the positive factors of independent study. Lifelong learning is defined as self-directed growth free from the traditional schooling procedures. Chapters discuss the following: the lifelong learner; profiles of such learners in action; how to be…

  2. The Mighty Caloris

    NASA Image and Video Library

    2015-02-23

    This is an MDIS mosaic of the mighty Caloris basin, Mercury's youngest large impact basin. Caloris has been filled by volcanic plains that are distinctive in color from the surrounding terrain. Subsequent craters have excavated low-reflectance material from beneath these volcanic plains, possibly giving clues to the composition of the basin floor. The basin interior has a complex tectonic history. The interior smooth plains have an area approximately the area of Alaska! Over 640 Rhode Islands would fit inside of this massive basin. http://photojournal.jpl.nasa.gov/catalog/PIA19213

  3. Very Low-Calorie Diets

    MedlinePlus

    ... list of resources ​​. Alternate Language URL Very Low-calorie Diets Page Content What is a VLCD? Should ... weight? Research ​ Clinical Trials Resources​ A very low-calorie diet (VLCD) is not just any diet that ...

  4. Calories and fat per serving (image)

    MedlinePlus

    ... and stores the rest in the form of fat. A calorie is a calorie, whether it comes ... between them is the number of calories, nutrients, fat, and other ingredients in a typical serving . Calories ...

  5. Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

    PubMed

    Das, Sai Krupa; Roberts, Susan B; Bhapkar, Manjushri V; Villareal, Dennis T; Fontana, Luigi; Martin, Corby K; Racette, Susan B; Fuss, Paul J; Kraus, William E; Wong, William W; Saltzman, Edward; Pieper, Carl F; Fielding, Roger A; Schwartz, Ann V; Ravussin, Eric; Redman, Leanne M

    2017-02-22

    Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m(2)) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM

  6. Fibroblast Growth Factor 21 Is Not Required for the Reductions in Circulating Insulin-Like Growth Factor-1 or Global Cell Proliferation Rates in Response to Moderate Calorie Restriction in Adult Mice

    PubMed Central

    Nag, Nitish; Kharitonenkov, Alexei; Adams, Andrew C.; Hellerstein, Marc K.

    2014-01-01

    Calorie restriction (CR) delays aging and extends lifespan in numerous organisms, including mice. Down-regulation of the somatotropic axis, including a reduction in insulin-like growth factor-1 (IGF-1), likely plays an important role in CR-induced lifespan extension, possibly by reducing cell proliferation rates, thereby delaying replicative senescence and inhibiting tumor promotion. Accordingly, elucidating the mechanism(s) by which IGF-1 is reduced in response to CR holds therapeutic potential in the fight against age-related diseases. Up-regulation of fibroblast growth factor 21 (FGF21) is one possible mechanism given that FGF21 expression is induced in response to nutritional deprivation and has been implicated as a negative regulator of IGF-1 expression. Here we investigated alterations in hepatic growth hormone (GH)-mediated IGF-1 production and signaling as well as the role of FGF21 in the regulation of IGF-1 levels and cell proliferation rates in response to moderate CR in adult mice. We found that in response to moderate CR, circulating GH and hepatic janus kinase 2 (JAK2) phosphorylation levels are unchanged but that hepatic signal transducer and activator of transcription 5 (STAT5) phosphorylation levels are reduced, identifying STAT5 phosphorylation as a potential key site of CR action within the somatotropic axis. Circadian measurements revealed that the relative level of FGF21 expression is both higher and lower in CR vs. ad libitum (AL)-fed mice, depending on the time of measurement. Employing FGF21-knockout mice, we determined that FGF21 is not required for the reduction in IGF-1 levels or cell proliferation rates in response to moderate CR. However, compared to AL-fed WT mice, AL-fed FGF21-knockout mice exhibited higher basal rates of cell proliferation, suggesting anti-mitotic effects of FGF21. This work provides insights into both GH-mediated IGF-1 production in the context of CR and the complex network that regulates FGF21 and IGF-1 expression

  7. The inclusion of a partial meal replacement with or without inulin to a calorie restricted diet contributes to reach recommended intakes of micronutrients and decrease plasma triglycerides: A randomized clinical trial in obese Mexican women.

    PubMed Central

    2012-01-01

    Background Obesity is a major public health problem in many poor countries where micronutrient deficiencies are prevalent. A partial meal replacement may be an effective strategy to decrease obesity and increase micronutrient intake in such populations. The objective was to evaluate the efficacy of a partial meal replacement with and without inulin on weight reduction, blood lipids and micronutrients intake in obese Mexican women. Methods In a randomized controlled clinical trial 144 women (18–50 y) with BMI ≥ 25 kg/m2, were allocated into one of the following treatments during 3 months: 1) Two doses/d of a partial meal replacement (PMR), 2) Two doses/d of PMR with inulin (PMR + I) , 3) Two doses/d of 5 g of inulin (INU) and 4) Control group (CON). All groups received a low calorie diet (LCD). Weight, height, hip and waist circumference were measured every 2 weeks and body composition, lipids and glucose concentration and nutrient intake were assessed at baseline and after 3 months. Results All groups significantly reduced weight, BMI, waist and hip circumference. Differences between groups were only observed in BMI and weight adjusted changes: At 45 days PMR group lost more weight than INU and CON groups by 0.9 and 1.2Kg, respectively. At 60 days, PMR + I and PMR groups lost more weight than in INU by 0.7 and 1Kg, respectively. Subjects in PMR, PMR + I and INU significantly decreased triglycerides. Energy intake was reduced in all groups. Fiber intake increased in PMR + I and INU groups. Some minerals and vitamins intakes were higher in PMR and PMR + I compared with INU and CON groups. Conclusion Inclusion of PMR with and without inulin to a LCD had no additional effect on weight reduction than a LCD alone but reduced triglycerides and improved intake of micronutrients during caloric restriction. PMR could be a good alternative for obese populations with micronutrient deficiencies. ClinicalTrials.Gov ID NCT01505023 PMID

  8. Orientale and Caloris

    USGS Publications Warehouse

    McCauley, J.F.

    1977-01-01

    Applications of experimental explosion-crater data to Orientale and recent geologic mapping of the basin have produced a new stratigraphy and genetic model for Orientale that are also applicable to Caloris. The inner-basin scarp of Orientale is thought to be a bench separating the upper parts of the basin from its deep bowl-shaped interior. The elongated and complexly fractured domes of the basin floor formed by inward compression in the terminal stages of the cratering sequence. The Inner Montes Rook are considered a central peak ring. The Montes Rook and the nonlineated knobby and associated smoother materials that overlie the Cordillera scarp around much of its circumference are the uppermost parts of the overturned rim flap which formed early in the cratering event. The knobs and smaller massifs are probably coherent blocks quarried from deep within the moon. They were among the last materials to leave the basin and had little radial momentum unlike the lineated Hevelius which formed earlier by disaggregation of the rim flap, secondary cratering, and the ground surge. The Cordillera scarp, best seen on the east side of the basin but poorly developed and discontinuous on the west, is a primary feature formed early in the crater excavation process by basinward motions of the walls and the fractured zone beyond the rim of the expanding cavity. The Cordillera scarp is overlain by ejecta over most of its extent, and post-basin internal slumping, previously thought to be important, must be a subordinate process in development of the scarp. The basin fill in Caloris has no counterpart in Orientale but the materials between the most prominent scarp and the weakly developed outer scarp appear to be the degraded and possibly mantled equivalents of the massifs and knobs associated with the Montes Rook. The radially lineated terrain that generally lies beyond the outer scarp of Caloris is considered the subdued counterpart of the Hevelius Formation, which generally shows

  9. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study

    PubMed Central

    Dessein, P; Shipton, E; Stanwix, A; Joffe, B; Ramokgadi, J

    2000-01-01

    OBJECTIVES—Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout.
METHODS—Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrolment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD).
RESULTS—At onset, the body mass index (BMI) was 30.5 (8.1) kg/m2. Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0.9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0.004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05).

  10. Lifelong Learning: Emergent Enactments

    ERIC Educational Resources Information Center

    Edwards, Richard

    2010-01-01

    This article represents four emergences through which to explore the significance of lifelong learning. Drawing in particular on complexity theory and actor-network theory, it seeks to develop an understanding of the reductions and emergences, and purifications and translations to which lifelong learning is subject. To do this, the article also…

  11. Lifelong Learning: Emergent Enactments

    ERIC Educational Resources Information Center

    Edwards, Richard

    2010-01-01

    This article represents four emergences through which to explore the significance of lifelong learning. Drawing in particular on complexity theory and actor-network theory, it seeks to develop an understanding of the reductions and emergences, and purifications and translations to which lifelong learning is subject. To do this, the article also…

  12. Nurturing Lifelong Readers

    ERIC Educational Resources Information Center

    Judkins, Gerri

    2010-01-01

    In this paper the author relates how the thing he enjoys most about his job as a school librarian is nurturing lifelong readers, in particular readers of children's literature. In talking about nurturing lifelong readers and, referring to students, staff and school librarians, the author discusses: (1) The Southwell Library Programme; (2) The Lit…

  13. Very Low-Calorie Diets

    MedlinePlus

    ... calorie Diets Related Topics Section Navigation Weight Management Bariatric Surgery Definition & Facts Types of Bariatric Surgery Bariatric Surgery Benefits Bariatric Surgery Side Effects Potential ...

  14. Predictors of total calories purchased at fast-food restaurants: restaurant characteristics, calorie awareness, and use of calorie information.

    PubMed

    Brissette, Ian; Lowenfels, Ann; Noble, Corina; Spicer, Deborah

    2013-01-01

    To examine purchase patterns at fast-food restaurants and their relation to restaurant characteristics, customer characteristics, and use of calorie information. Cross-sectional survey. Fast-food restaurants in New York State. Adult fast-food restaurant customers (n = 1,094). Restaurant characteristics (fast-food chain type, presence of calorie labels, and poverty of location), participant characteristics (demographics, calorie knowledge, awareness, and use), and customer purchasing patterns (ordering low-calorie or no beverage, small or no fries, or < 3 items) were used as predictors of total calories purchased. Multiple regression. In a regression model including restaurant and customer characteristics, fast-food chain customer age, sex, calorie use, and calorie awareness were independently associated with total calories purchased (all P < .05; model R2 = .19). When 3 purchasing patterns were added to the model, calorie use (P = .005), but not calorie awareness, remained associated with total calories purchased. The 3 purchase patterns collectively accounted for the majority of variance in calorie totals (Δ model R2 = .40). Promoting use of calorie information, purchase strategies, and calorie awareness represents complementary ways to support lower-calorie choices at fast-food chains. Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  15. Lifelong Qualifications. Developing Qualifications To Support Lifelong Learners.

    ERIC Educational Resources Information Center

    Wilson, Peter

    If Britain is to deliver a genuine framework for lifelong learning in the 21st century, a qualifications system must be developed to support this framework. The National Qualifications Framework may not be fit for the purpose of supporting lifelong learning. A policy on lifelong learning must explicitly connect with qualifications reform to have…

  16. The Next Step: Lifelong Learning

    ERIC Educational Resources Information Center

    Mondale, Walter F.

    1976-01-01

    Schools do not exist in a vacuum and neither do people. That fact is propelling the U.S. toward a national policy on lifelong learning. Provisions of the Senate Lifelong Learning Bill are included. (LBH)

  17. Lifelong Learning and Prosperity.

    ERIC Educational Resources Information Center

    Couture, Pauline

    1993-01-01

    Discusses the need for lifelong learning to maintain a presence in a world economy. Looks at the widening gap between rich and poor and its relation to educational level and suggests that more emphasis must be placed on upgrading the skills of blue collar workers. (JOW)

  18. Death and Lifelong Learning

    ERIC Educational Resources Information Center

    Schuller, Tom

    2011-01-01

    Lifelong learning has a crucial role in enabling individuals to handle key transition points in their lives, but what can education do to prepare them for the final, inevitable transition. Some of the educational contribution to managing the final transition is very broad, a matter of general enlightenment. But there are some more specific…

  19. Loans for Lifelong Learning.

    ERIC Educational Resources Information Center

    Fletcher, Mick, Ed.

    This collection of eight papers looks at how a system of loans for lifelong learning in Great Britain and New Zealand might be positioned. It examines where such loans might work best and where they seem inappropriate. In particular, the collection assembles the available evidence about the role and impact of loans in the world of education and…

  20. Invitation to Lifelong Learning.

    ERIC Educational Resources Information Center

    Gross, Ronald, Ed.

    In this anthology of readings, 28 scholars and educators consider the theoretical and practical forces that shape the concept of lifelong learning. After Ronald Gross's introduction, the first section begins its consideration of the Western tradition in adult learning with Plato's metaphor of the cave and includes Pico della Mirandola's essay on…

  1. Invitation to Lifelong Learning.

    ERIC Educational Resources Information Center

    Gross, Ronald, Ed.

    In this anthology of readings, 28 scholars and educators consider the theoretical and practical forces that shape the concept of lifelong learning. After Ronald Gross's introduction, the first section begins its consideration of the Western tradition in adult learning with Plato's metaphor of the cave and includes Pico della Mirandola's essay on…

  2. Pakistan: Lifelong Literacy Project

    ERIC Educational Resources Information Center

    Literacy Work, 1974

    1974-01-01

    The article reports on progress towards lifelong literacy education in Pakistan, covering the project's introduction in 1972 and reviewing current activities in brief but concrete sketches of such topics as materials, operation of projects, and student drop-outs. Appendixes include a map and occupational breakdowns of teachers and students. (AJ)

  3. Lifelong Learning and Politics.

    ERIC Educational Resources Information Center

    Richardson, Penelope L.

    1979-01-01

    States that community colleges are in a good position to be centers of lifelong education and that adult educators must engage in politics in order to promote learning opportunities for adults. Suggests legislative, administrative, judicial, and electoral strategies for adult educators to use in influencing policymakers to support lifelong…

  4. Lifelong Learning: Capabilities and Aspirations

    ERIC Educational Resources Information Center

    Ilieva-Trichkova, Petya

    2016-01-01

    The present paper discusses the potential of the capability approach in conceptualizing and understanding lifelong learning as an agency process, and explores its capacity to guide empirical studies on lifelong learning. It uses data for 20 countries from the Adult Education Survey (2007; 2011) and focuses on aspirations for lifelong learning. The…

  5. New Technology and Lifelong Learning.

    ERIC Educational Resources Information Center

    Thorpe, Mary

    Key issues related to the relationship between new technology and lifelong learning in the United Kingdom and elsewhere were identified through reviews of the literature on information and communications technology (ICT) and the literature on lifelong learning. Two overarching issues related to the interplay of new technology and lifelong learning…

  6. Calorie Underestimation When Buying High-Calorie Beverages in Fast-Food Contexts.

    PubMed

    Franckle, Rebecca L; Block, Jason P; Roberto, Christina A

    2016-07-01

    We asked 1877 adults and 1178 adolescents visiting 89 fast-food restaurants in New England in 2010 and 2011 to estimate calories purchased. Calorie underestimation was greater among those purchasing a high-calorie beverage than among those who did not (adults: 324 ±698 vs 102 ±591 calories; adolescents: 360 ±602 vs 198 ±509 calories). This difference remained significant for adults but not adolescents after adjusting for total calories purchased. Purchasing high-calorie beverages may uniquely contribute to calorie underestimation among adults.

  7. Adaptations of intestinal nutrient transport to chronic caloric restriction in mice.

    PubMed

    Casirola, D M; Rifkin, B; Tsai, W; Ferraris, R P

    1996-07-01

    Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.

  8. Soluble CD163 is associated with CD163 mRNA expression in adipose tissue and with insulin sensitivity in steady-state condition but not in response to calorie restriction.

    PubMed

    Kračmerová, Jana; Rossmeislová, Lenka; Kováčová, Zuzana; Klimčáková, Eva; Polák, Jan; Tencerová, Michaela; Mališová, Lucia; Štich, Vladimír; Langin, Dominique; Šiklová, Michaela

    2014-03-01

    Soluble CD163 (sCD163) was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Two cohorts of subjects were examined in the study. Cohort 1 included 42 women with a wide range of body mass index (17-48 kg/m(2)); cohort 2 included 27 obese women who followed a dietary intervention consisting of 1 month of a very low-calorie diet and 5 months of a weight-stabilization period. Serum levels of CD163 and mRNA expression of CD163 and CD68 in sc and visceral (visc) AT were determined, and insulin sensitivity [expressed as glucose disposal rate (GDR)] was measured in cohort 1. In cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors [TNF-α-converting enzyme (TACE) and tissue inhibitor of metalloproteinase (TIMP3)] in sc AT were examined and GDR was measured before and during dietary intervention. In cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both sc and visc AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD68, TACE, and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR, there was no correlation between the changes of these two variables. sCD163 correlates with CD163 mRNA expression in sc and visc AT and with whole-body insulin sensitivity in the steady-state condition. These associations are not observed with respect to the diet-induced changes during a weight-reducing hypocaloric diet.

  9. Leading Through Lifelong Learning.

    PubMed

    Lambert, Dawn

    2016-07-01

    School nurses, as leaders, are able to exhibit leadership skills through embracing, advocating for, and demonstrating a commitment to lifelong learning. With the continual changes in healthcare and technology, ongoing education is essential to maintain a high standard of expertise and practice. School nurses have many opportunities for continuing education. This article will briefly explore various levels of continuing education, as well as relating ongoing learning to leadership principles. © 2016 The Author(s).

  10. Who Is the Lifelong Learner? Globalization, Lifelong Learning and Hermeneutics

    ERIC Educational Resources Information Center

    Uggla, Bengt Kristensson

    2008-01-01

    The aim of this essay is to elaborate on the inner connection between three such diverse entities as lifelong learning, globalization and hermeneutics. After placing lifelong learning in a societal context framed by globalization, my intention is to reflect on the prerequisites for introducing a hermeneutical contribution to the understanding of…

  11. Who Is the Lifelong Learner? Globalization, Lifelong Learning and Hermeneutics

    ERIC Educational Resources Information Center

    Uggla, Bengt Kristensson

    2008-01-01

    The aim of this essay is to elaborate on the inner connection between three such diverse entities as lifelong learning, globalization and hermeneutics. After placing lifelong learning in a societal context framed by globalization, my intention is to reflect on the prerequisites for introducing a hermeneutical contribution to the understanding of…

  12. Long-term, calorie-restricted intake of a high-fat diet in rats reduces impulse control and ventral striatal D2 receptor signalling - two markers of addiction vulnerability.

    PubMed

    Adams, Wendy K; Sussman, Jacob L; Kaur, Sukhbir; D'souza, Anna M; Kieffer, Timothy J; Winstanley, Catharine A

    2015-12-01

    High impulsivity, mediated through ventral striatal dopamine signalling, represents an established risk factor for substance abuse, and may likewise confer vulnerability to pathological overeating. Mechanistically, the assumption is that trait impulsivity facilitates the initiation of maladaptive eating styles or choices. However, whether consumption of appetitive macronutrients themselves causes deficits in impulse control and striatal signalling, thereby contributing to cognitive changes permissive of overeating behaviour, has yet to be considered. We examined the effects of chronic maintenance on restricted equicaloric, but high-fat or high-sugar, diets (48 kcal/day; 60 kcal% fat or sucrose) on rats' performance in the five-choice serial reaction time task, indexing impulsivity and attention. Markers of dopamine signalling in the dorsal and ventral striatum, and plasma insulin and leptin levels, were also assessed. Rats maintained on the high-fat diet (HFD) were more impulsive, whereas the high-sugar diet (HSD) did not alter task performance. Importantly, body weight and hormone levels were similar between groups when behavioural changes were observed. Maintenance on HFD, but not on HSD, reduced the levels of dopamine D2 receptor (D2 R), cAMP response element-binding protein (CREB) and phosphophorylated CREB (Ser133) proteins in the ventral, but not dorsal, striatum. D2 R expression in the ventral striatum also negatively correlated with impulsive responding, independently of diet. These data indicate that chronic exposure to even limited amounts of high-fat foods may weaken impulse control and alter neural signalling in a manner associated with vulnerability to addictions - findings that have serious implications for the propagation of uncontrolled eating behaviour in obesity and binge-eating disorder.

  13. Explorations of Lifelong Learning Ethics

    ERIC Educational Resources Information Center

    Igbinomwanhia, John

    2009-01-01

    The methodological approaches that were used in this research were ethnographic, quantitative and analysis of post-compulsory education policy documents 1945-2007. The article aims to explore the issues of ethics in lifelong learning, and an alternative approach to the analysis of the impact of lifelong learning policy, by focusing research…

  14. Lifelong Learning on the Web.

    ERIC Educational Resources Information Center

    Brown, Brian

    As a medium for delivering lifelong learning, the Internet makes it possible to customize education to individual needs, deliver education anywhere and anytime, and enable learners to interact with other learners and teachers collaboratively to solve problems and learn new skills. Nevertheless, as a medium for delivering lifelong learning, the…

  15. International Perspectives on Lifelong Learning.

    ERIC Educational Resources Information Center

    Holford, John, Ed.; Jarvis, Peter, Ed.; Griffin, Colin, Ed.

    This book contains 30 papers providing international perspectives on lifelong learning. The following papers are included: "Edgar Faure after 25 Years" (Roger Boshier); "Public Rhetoric and Public Policy" (Colin Griffin); "Lifelong Learning and the European Union" (Barry J. Hake); "Critical Perspectives and New…

  16. International Perspectives on Lifelong Learning.

    ERIC Educational Resources Information Center

    Holford, John, Ed.; Jarvis, Peter, Ed.; Griffin, Colin, Ed.

    This book contains 30 papers providing international perspectives on lifelong learning. The following papers are included: "Edgar Faure after 25 Years" (Roger Boshier); "Public Rhetoric and Public Policy" (Colin Griffin); "Lifelong Learning and the European Union" (Barry J. Hake); "Critical Perspectives and New…

  17. Online Education for Lifelong Learning

    ERIC Educational Resources Information Center

    Inoue, Yukiko, Ed.

    2007-01-01

    Distance education is rapidly becoming the global trend for lifelong learning. This book emphasizes the importance of conceptual understanding of online distance learning and focuses on theoretical and practical challenges of online teaching and learning. It illustrates lifelong learning strategies and how technology can support the course…

  18. Who Pays for Lifelong Learning?

    ERIC Educational Resources Information Center

    Watson, Louise

    Structural change in the economy has seen the emergence of human resource skills as an important intangible input to the value-adding process. The fastest growing sectors of the economy employ workers with high levels of skill. This has led to the development of a lifelong learning policy agenda that argues lifelong learning is the key to economic…

  19. Online Education for Lifelong Learning

    ERIC Educational Resources Information Center

    Inoue, Yukiko, Ed.

    2007-01-01

    Distance education is rapidly becoming the global trend for lifelong learning. This book emphasizes the importance of conceptual understanding of online distance learning and focuses on theoretical and practical challenges of online teaching and learning. It illustrates lifelong learning strategies and how technology can support the course…

  20. Federal Programs Supporting Lifelong Learning.

    ERIC Educational Resources Information Center

    Christoffel, Pam, Comp.

    Approximately 275 Federal programs support some form of lifelong learning. While the majority of the lifelong learning programs are administered by the various agencies within HEW, a significant number of programs are run by such Federal agencies as the Department of Justice, the National Foundation on the Arts and Humanities, and the Smithsonian…

  1. Macronutrients and obesity: revisiting the calories in, calories out framework.

    PubMed

    Riera-Crichton, Daniel; Tefft, Nathan

    2014-07-01

    Recent clinical research has studied weight responses to varying diet composition, but the contribution of changes in macronutrient intake and physical activity to rising population weight remains controversial. Research on the economics of obesity typically assumes a "calories in, calories out" framework, but a weight production model separating caloric intake into carbohydrates, fat, and protein, has not been explored in an economic framework. To estimate the contributions of changes in macronutrient intake and physical activity to changes in population weight, we conducted dynamic time series and structural VAR analyses of U.S. data between 1974 and 2006 and a panel analysis of 164 countries between 2001 and 2010. Findings from all analyses suggest that increases in carbohydrates are most strongly and positively associated with increases in obesity prevalence even when controlling for changes in total caloric intake and occupation-related physical activity. Our structural VAR results suggest that, on the margin, a 1% increase in carbohydrates intake yields a 1.01 point increase in obesity prevalence over 5 years while an equal percent increase in fat intake decreases obesity prevalence by 0.24 points.

  2. Stratigraphy of the Caloris basin, Mercury

    USGS Publications Warehouse

    McCauley, J.F.; Guest, J.E.; Schaber, G.G.; Trask, N.J.; Greeley, R.

    1981-01-01

    The 1300-km-diameter Caloris impact basin is surrounded by well-defined ejecta units that can be recognized from more than 1000 km, radially outward from the basin edge. A formal rock stratigraphic nomenclature is proposed for the Caloris ejecta units, which are collectively called the Caloris Group. Each of the individual formations within the Group are described and compared to similar rock units associated with the lunar Imbrium and Orientale basins. A crater degradation chronology, linked the the Caloris event, is also proposed to assist in stratigraphic correlation on a Mercury-wide basis. ?? 1981.

  3. Calorie Changes in Large Chain Restaurants

    PubMed Central

    Bleich, Sara N.; Wolfson, Julia A.; Jarlenski, Marian P.

    2015-01-01

    Introduction Large chain restaurants reduced the number of calories in newly introduced menu items in 2013 by about 60 calories (or 12%) relative to 2012. This paper describes trends in calories available in large U.S. chain restaurants to understand whether previously documented patterns persist. Methods Data (a census of items for included restaurants) were obtained from the MenuStat project. This analysis included 66 of the 100 largest U.S. restaurants that are available in all three 3 of the data (2012–2014; N=23,066 items). Generalized linear models were used to examine: (1) per-item calorie changes from 2012 to 2014 among items on the menu in all years; and (2) mean calories in new items in 2013 and 2014 compared with items on the menu in 2012 only. Data were analyzed in 2014. Results Overall, calories in newly introduced menu items declined by 71 (or 15%) from 2012 to 2013 (p=0.001) and by 69 (or 14%) from 2012 to 2014 (p=0.03). These declines were concentrated mainly in new main course items (85 fewer calories in 2013 and 55 fewer calories in 2014; p=0.01). Although average calories in newly introduced menu items are declining, they are higher than items common to the menu in all 3 years. No differences in mean calories among items on menus in 2012, 2013, or 2014 were found. Conclusions The previously observed declines in newly introduced menu items among large restaurant chains have been maintained, which suggests the beginning of a trend toward reducing calories. PMID:26163168

  4. Protein requirements with very low calorie diets.

    PubMed

    Blackburn, G L

    1984-01-01

    The goal of the dietary treatment of obesity is to reduce the patient's weight with minimum risk. This is accomplished by a dietary regimen which allows a preferential loss of body fat with a preservation of lean body mass. Total fasting leads to a loss of 150 grams of nitrogen in the first month alone. In a study by Hoffer et al. reported below, two levels of dietary protein were compared for their effects on nitrogen balance in 17 obese women on a low calorie (500 cal) weight reduction diet. After three weeks of adaptation to the diets, the group given 0.8 grams protein/kg were in -2 grams nitrogen balance while the group given 1.5 grams protein/kg were at zero nitrogen balance. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted. While weight loss is the obvious goal for obese persons, a careful examination of the composition of the weight loss (protein, fat, water) is essential in defining the optimal dietary regimen.

  5. Protein and calorie effects on progression of induced chronic renal failure in cats.

    PubMed

    Finco, D R; Brown, S A; Brown, C A; Crowell, W A; Sunvold, G; Cooper, T L

    1998-05-01

    To determine effects of dietary protein and calories on progression of induced chronic renal failure in cats. 28 young adult female cats. Renal mass was reduced surgically, and glomerular filtration rate (GFR) was determined. Cats were alloted to 4 groups of 7 with similar mean GFR (1.52 to 1.55 ml/min/kg of body weight). Diets were formulated to provide: low protein and calorie (diet A), low protein and high calorie (diet B), high protein and low calorie (diet C), and high protein and calorie (diet D) intakes. Cats were fed their prescribed diet for 12 months, then blood and urine biochemical variables were measured, after which kidney specimens were examined microscopically. Protein intake by cats of groups C and D (9.0 g/d/kg) was substantially greater than that by cats of groups A and B (5.3 and 5.2 g/d/kg, respectively). Caloric intake by cats of groups B and D (73 and 71 calories/d/kg, respectively) was greater than that by cats of groups A and C (58 and 55 calories/d/kg, respectively). Renal glomerular lesions were mild and not affected by protein, calories or their interactions. Nonglomerular lesions, though mild, were significantly influenced by calorie intake, but not by protein or calorie-protein interactions. The GFR did not decrease in any group. Urine protein-to-creatinine ratio increased significantly in all groups after reduction of renal mass, but values from all groups remained within the reference range (0 to 0.3). Diets replete in protein were not associated with increased severity of glomerular or nonglomerular renal lesions, increased proteinuria, or decreased GFR. Diets replete in calories were not associated with increased severity of glomerular lesions, but were associated with mild increase of nonglomerular lesions. Factors other than protein and calorie intake must be considered potential causes of progression of renal failure in cats. Results raise questions about the practice of restricting quantity of protein in the diet of cats with

  6. Methionine restriction and lifespan control

    PubMed Central

    Lee, Byung Cheon; Kaya, Alaattin; Gladyshev, Vadim N.

    2016-01-01

    Dietary restriction (DR) without malnutrition is associated with longevity in various organisms. However, it has also been shown that reduced calorie intake is often ineffective in extending lifespan. Selecting optimal dietary regimens for DR studies is complicated, as the same regimen may lead to different outcomes depending on genotype and environmental factors. Recent studies suggested that interventions such as moderate protein restriction with/without adequate nutrition (e.g. particular amino acids or carbohydrates) may have additional beneficial effects mediated by certain metabolic and hormonal factors implicated in the biology of aging, regardless of total calorie intake. In particular, it was shown that restriction of a single amino acid, methionine, can mimic the effects of DR and extend lifespan in various model organisms. We discuss beneficial effects of methionine-restricted (MR) diet, the molecular pathways involved, and the use of this regimen in longevity interventions. PMID:26663138

  7. Knowledge of Recommended Calorie Intake and Influence of Calories on Food Selection Among Canadians.

    PubMed

    McCrory, Cassondra; Vanderlee, Lana; White, Christine M; Reid, Jessica L; Hammond, David

    2016-03-01

    To examine knowledge of recommended daily calorie intake, use of calorie information, and sociodemographic correlates between knowledge and use. Population-based, random digit-dialed phone surveys. Canadian adults (n = 1,543) surveyed between October and December, 2012. Knowledge of recommended calorie intake and use of calorie information when purchasing food. Regression models, adjusting for sociodemographics and diet-related measures. Overall, 24% of participants correctly stated their recommended daily calorie intake; the majority (63%) underestimated it, whereas few (4%) overestimated it. Females, younger participants, those with a higher income and more education, and those who consumed fruits and vegetables at least 5 times daily were significantly more likely to state recommended intake correctly. Most respondents (82%) reported considering calories when selecting foods. Respondents considered calories more often if they were female, had a higher income and more education, perceived themselves to be overweight, were actively trying to control their weight, reported a healthier diet, or consumed fruits and vegetables at least 5 times daily. Although most Canadians reported using calorie information to guide their food choices, few knew their daily recommended calorie intake. To promote healthy weights, policy initiatives, including education regarding daily calorie intake and changes to the Nutrition Facts table, may help consumers make better choices about food. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  8. Social media for lifelong learning.

    PubMed

    Kind, Terry; Evans, Yolanda

    2015-04-01

    Learning is ongoing, and can be considered a social activity. In this paper we aim to provide a review of the use of social media for lifelong learning. We start by defining lifelong learning, drawing upon principles of continuous professional development and adult learning theory. We searched Embase and MEDLINE from 2004-2014 for search terms relevant to social media and learning. We describe examples of lifelong learners using social media in medical education and healthcare that have been reported in the peer-reviewed literature. Medical or other health professions students may have qualities consistent with being a lifelong learner, yet once individuals move beyond structured learning environments they will need to recognize their own gaps in knowledge and skills over time and be motivated to fill them, thereby incorporating lifelong learning principles into their day-to-day practice. Engagement with social media can parallel engagement in the learning process over time, to the extent that online social networking fosters feedback and collaboration. The use of social media and online networking platforms are a key way to continuously learn in today's information sharing society. Additional research is needed, particularly rigorous studies that extend beyond learner satisfaction to knowledge, behaviour change, and outcomes.

  9. The effects of calorie information on food selection and intake.

    PubMed

    Girz, L; Polivy, J; Herman, C P; Lee, H

    2012-10-01

    To examine the effects of calorie labeling on food selection and intake in dieters and non-dieters, and to explore whether expectations about food healthfulness moderate these effects. Participants were presented with a menu containing two items, a salad and a pasta dish. The menu had (a) no calorie information, (b) information that the salad was low in calories and the pasta was high in calories, (c) information that the salad was high in calories and the pasta was low in calories or (d) information that both were high in calories (study 2 only). Calorie labels influenced food selection for dieters, but not for non-dieters. Dieters were more likely to order salad when the salad was labeled as low in calories and more likely to order pasta, even high-calorie pasta, when the salad was labeled as high in calories. Participants who chose high-calorie foods over low-calorie foods did not eat less in response to calorie information, although non-dieters reduced their intake somewhat when calorie labels were put in the context of recommended daily calories. The results suggest that the rush to provide calorie information may not prove to be the best approach to fighting the obesity epidemic.

  10. Lifelong exposure to dietary isoflavones reduces risk of obesity in ovariectomized Wistar rats.

    PubMed

    Kurrat, Anne; Blei, Tina; Kluxen, Felix M; Mueller, Dennis R; Piechotta, Marion; Soukup, Sebastian T; Kulling, Sabine E; Diel, Patrick

    2015-12-01

    Traditional Asian diet rich in soy isoflavones (ISOs) is discussed to be linked to a lower obesity prevalence. In lifelong and short-term exposure scenarios we investigated effects of an ISO-rich diet on the body composition and development of obesity in female rats. Female Wistar rats grew up on ISO-free or ISO-rich control diet (CON ISO: 467 mg/kg diet). Starting postnatal day 83, ovariectomized and intact animals received high calorie Western diet (WD) in the absence or presence of ISO (WD ISO: 431 mg/kg diet) for 12 weeks to induce obesity or maintained on respective control diet (CON). One group starting ISO exposure after ovariectomy mimics short-term ISO exposure in postmenopausal Western women. Lifelong but not short-term ISO exposure resulted in reduced body weight, visceral fat mass, serum leptin, and smaller adipocytes. ISO decreased hepatic SREBP-1c, ACC, FAS, and PPARγ mRNA expression in nonobese animals. Moreover, ovariectomy reduced skeletal muscle weight, which was antagonized by both short-term and lifelong ISO exposure. Our results indicate that in female rats lifelong but not short-term ISO intake reduces the risk to develop obesity. Furthermore, lifelong and short-term ISO exposure may antagonize loss of skeletal muscle mass induced by ovariectomy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Calorie count - sodas and energy drinks

    MedlinePlus

    ... ency/patientinstructions/000888.htm Calorie count - sodas and energy drinks To use the sharing features on this ... to have a few servings of soda or energy drinks a day without thinking about it. Like ...

  12. Restaurants With Calories Displayed On Menus Had Lower Calorie Counts Compared To Restaurants Without Such Labels

    PubMed Central

    Bleich, Sara N.; Wolfson, Julia A.; Jarlenski, Marian P.; Block, Jason P.

    2016-01-01

    Beginning in December 2016, calorie labeling on menus will be mandatory for US chain restaurants and many other establishments that serve food, such as ice cream shops and movie theaters. But before the federal mandate kicks in, several large chain restaurants have begun to voluntarily display information about the calories in the items on their menus. This increased transparency may be associated with lower overall calorie content of offered items. This study used data for the period 2012–14 from the MenuStat project, a data set of menu items at sixty-six of the largest US restaurant chains. We compared differences in calorie counts of food items between restaurants that voluntarily implemented national menu labeling and those that did not. We found that the mean per item calorie content in all years was lower for restaurants that voluntarily posted information about calories (the differences were 139 calories in 2012, 136 in 2013, and 139 in 2014). New menu items introduced in 2013 and 2014 showed a similar pattern. Calorie labeling may have important effects on the food served in restaurants by compelling the introduction of lower-calorie items. PMID:26526245

  13. Restaurants With Calories Displayed On Menus Had Lower Calorie Counts Compared To Restaurants Without Such Labels.

    PubMed

    Bleich, Sara N; Wolfson, Julia A; Jarlenski, Marian P; Block, Jason P

    2015-11-01

    Beginning in December 2016, calorie labeling on menus will be mandatory for US chain restaurants and many other establishments that serve food, such as ice cream shops and movie theaters. But before the federal mandate kicks in, several large chain restaurants have begun to voluntarily display information about the calories in the items on their menus. This increased transparency may be associated with lower overall calorie content of offered items. This study used data for the period 2012-14 from the MenuStat project, a data set of menu items at sixty-six of the largest US restaurant chains. We compared differences in calorie counts of food items between restaurants that voluntarily implemented national menu labeling and those that did not. We found that the mean per item calorie content in all years was lower for restaurants that voluntarily posted information about calories (the differences were 139 calories in 2012, 136 in 2013, and 139 in 2014). New menu items introduced in 2013 and 2014 showed a similar pattern. Calorie labeling may have important effects on the food served in restaurants by compelling the introduction of lower-calorie items. Project HOPE—The People-to-People Health Foundation, Inc.

  14. How to Choose a Lifelong Sport.

    ERIC Educational Resources Information Center

    Regin, Chuck

    1983-01-01

    Stresses the benefits of lifelong sports including self-expression, wholeness, relaxation, and physical health. Suggests methods of determining physical fitness status, setting goals, and selecting appropriate activities. Internal and external motivation for pursuing lifelong sports are discussed. (JAC)

  15. Height and calories in early childhood.

    PubMed

    Griffen, Andrew S

    2016-03-01

    This paper estimates a height production function using data from a randomized nutrition intervention conducted in rural Guatemala from 1969 to 1977. Using the experimental intervention as an instrument, the IV estimates of the effect of calories on height are an order of magnitude larger than the OLS estimates. Information from a unique measurement error process in the calorie data, counterfactuals results from the estimated model and external evidence from migration studies suggest that IV is not identifying a policy relevant average marginal impact of calories on height. The preferred, attenuation bias corrected OLS estimates from the height production function suggest that, averaging over ages, a 100 calorie increase in average daily calorie intake over the course of a year would increase height by 0.06 cm. Counterfactuals from the model imply that calories gaps in early childhood can explain at most 16% of the height gap between Guatemalan children and the US born children of Guatemalan immigrants. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Gender, Masculinities and Lifelong Learning

    ERIC Educational Resources Information Center

    Bowl, Marion, Ed.; Tobias, Robert, Ed.; Leahy, Jennifer, Ed.; Ferguson, Graeme, Ed.; Gage, Jeffrey, Ed.

    2012-01-01

    "Gender, Masculinities and Lifelong Learning" reflects on current debates and discourses around gender and education, in which some academics, practitioners and policy-makers have referred to a crisis of masculinity. This book explores questions such as: Are men under-represented in education? Are women outstripping men in terms of…

  17. Gender, Masculinities and Lifelong Learning

    ERIC Educational Resources Information Center

    Bowl, Marion, Ed.; Tobias, Robert, Ed.; Leahy, Jennifer, Ed.; Ferguson, Graeme, Ed.; Gage, Jeffrey, Ed.

    2012-01-01

    "Gender, Masculinities and Lifelong Learning" reflects on current debates and discourses around gender and education, in which some academics, practitioners and policy-makers have referred to a crisis of masculinity. This book explores questions such as: Are men under-represented in education? Are women outstripping men in terms of…

  18. Sustainable Assessment for Lifelong Learning

    ERIC Educational Resources Information Center

    Nguyen, Tham T. H.; Walker, Melanie

    2016-01-01

    This paper explores the alignment of assessment practices in universities and lifelong learning as a key process and outcome for expansive student development. It outlines Boud's approach to assessment, operationalises this to analyse practices in two contrasting national contexts: the sociology departments of the Midlands University in the UK and…

  19. Self directed and lifelong learning.

    PubMed

    Alexander, Sylvia; Kernohan, George; McCullagh, Paul

    2004-01-01

    Given the many changes that occur in medicine, health care and information technologies we need to prepare all our students to engage in self directed and life long learning. There is considerable opportunity for self-directed and lifelong learning in health informatics bringing together students in exciting global learning environments, where they have much greater freedom and flexibility in their studies and potentially a wider variety of resources available to them. Self-directed learning focuses on the process by which adults take control of their own learning, in particular how they set their own learning goals, locate appropriate resources, decide on which learning methods to use and evaluate their progress. Lifelong learning happens in a variety of formal and informal settings building on both intentional and incidental learning experiences. In a lifelong learning situation the tutor must relinquish the role of expert and assume the role of facilitator, guiding learners to uncover their own knowledge. Against a back drop of rapid advances in technology which can be used to both deliver course materials and provide enhanced learning opportunities, this chapter outlines the pedagogic principles and practices which underpin self-directed and lifelong learning.

  20. The Promise of Lifelong Learning

    ERIC Educational Resources Information Center

    Gouthro, Patricia A.

    2017-01-01

    This paper explores how Peter Jarvis's work offers a comprehensive grounding in many of the key principles and insights offered through the field of adult education. His work directs us to the different factors--psychological, social, economic and political required for understanding lifelong learning contexts. As scholars and educators, he…

  1. What's Become of Lifelong Learning?

    ERIC Educational Resources Information Center

    Dainton, Sheila

    2009-01-01

    The author's father left school aged 13 at the start of the Great Depression. When he finally found work the wealth of educational opportunity he encountered inspired him with a lifelong love of learning. He signed up for evening classes and loved anything and everything to do with what he proudly called self-improvement. As a novice to retirement…

  2. Lifelong Learning, Policy and Desire

    ERIC Educational Resources Information Center

    Lynch, Heather

    2008-01-01

    Recent lifelong learning policies have been criticized for creating an illusion of freedom whilst simultaneously reducing choice. The concept of desire permits engagement with the conscious and unconscious drives that underpin individual decision-making, which direct the life course. Utilizing the ideas of Hume and Spinoza, the present article…

  3. Re-Thinking Lifelong Learning

    ERIC Educational Resources Information Center

    Hinchliffe, Geoff

    2006-01-01

    The current dominant concept of lifelong learning has arisen from the pressures of globalisation, economic change and the needs of the "knowledge economy". Its importance is not disputed in this paper. However, its proponents often advocate it in a form which places unrealistic demands on the individual without at the same time addressing their…

  4. Lifelong Learning and Welfare Reform.

    ERIC Educational Resources Information Center

    Griffin, Colin

    1999-01-01

    An alternative perspective on lifelong learning locates it in culture, civil society, and leisure/consumption lifestyles. Distinctions between education and learning and markets and quasi-markets are used to explore policy models. The relationship to welfare reform policies is discussed. (Author/SK)

  5. Developing Local Lifelong Guidance Strategies.

    ERIC Educational Resources Information Center

    Watts, A. G.; Hawthorn, Ruth; Hoffbrand, Jill; Jackson, Heather; Spurling, Andrea

    1997-01-01

    Outlines the background, rationale, methodology, and outcomes of developing local lifelong guidance strategies in four geographic areas. Analyzes the main components of the strategies developed and addresses a number of issues relating to the process of strategy development. Explores implications for parallel work in other localities. (RJM)

  6. Fiction, Empathy and Lifelong Learning

    ERIC Educational Resources Information Center

    Jarvis, Christine

    2012-01-01

    The article aims to demonstrate that the impact of fiction on adult learning could be illuminated by a deeper engagement with research into empathy. It recognises that the lifelong learning literature acknowledges the importance of empathy in adult learning and that discussions of the role of fiction in adult learning often refer to fiction's…

  7. Lifelong Learning as Transitional Learning

    ERIC Educational Resources Information Center

    Glastra, Folke J.; Hake, Barry J.; Schedler, Petra E.

    2004-01-01

    Globalization and individualization have radically changed both the economic system and the personal life world in industrial or postindustrial nation-states. To survive hypercompetition and volatile consumer choice, learning organizations and a workforce engaged in lifelong learning are needed. Constructing "the good life" has become an…

  8. Fiction, Empathy and Lifelong Learning

    ERIC Educational Resources Information Center

    Jarvis, Christine

    2012-01-01

    The article aims to demonstrate that the impact of fiction on adult learning could be illuminated by a deeper engagement with research into empathy. It recognises that the lifelong learning literature acknowledges the importance of empathy in adult learning and that discussions of the role of fiction in adult learning often refer to fiction's…

  9. What's Become of Lifelong Learning?

    ERIC Educational Resources Information Center

    Dainton, Sheila

    2009-01-01

    The author's father left school aged 13 at the start of the Great Depression. When he finally found work the wealth of educational opportunity he encountered inspired him with a lifelong love of learning. He signed up for evening classes and loved anything and everything to do with what he proudly called self-improvement. As a novice to retirement…

  10. Toward Life-Long Reading.

    ERIC Educational Resources Information Center

    Duquette, Raymond J.

    Developing life-long reading habits is a process that should begin in elementary school. Children should be encouraged not only to read what has been approved for classroom use but also to look beyond classroom walls to read for interest and enjoyment. "Looking beyond the walls" is a parable that suggests that school curriculum go beyond the…

  11. Lifelong Learning in Hong Kong.

    ERIC Educational Resources Information Center

    Lee, Grace O. M.

    Despite recent attempts at implementation, the government must play a more active role in promoting lifelong learning in Hong Kong. They did little until 1989, when the Open Learning Institute (OLI) was established. The OLI was innovative because it provided degree level courses for adults, without concern for prerequisite academic qualifications.…

  12. A Look at Lifelong Learning.

    ERIC Educational Resources Information Center

    Dutton, Donnie

    Adults must continue to learn. The accelerating pace of cultural change has made today's knowledge and skills tomorrow's obsolescence. A society that makes its educational investment almost entirely in children and youth is on the way to becoming obsolete and is reducing its survival chances. To promote the cause of lifelong learning, we need to…

  13. Sustainable Assessment for Lifelong Learning

    ERIC Educational Resources Information Center

    Nguyen, Tham T. H.; Walker, Melanie

    2016-01-01

    This paper explores the alignment of assessment practices in universities and lifelong learning as a key process and outcome for expansive student development. It outlines Boud's approach to assessment, operationalises this to analyse practices in two contrasting national contexts: the sociology departments of the Midlands University in the UK and…

  14. International Concepts and Agendas of Lifelong Learning

    ERIC Educational Resources Information Center

    Schuetze, Hans G.

    2006-01-01

    International organisations were the main proponents of Lifelong Learning when the concept was first developed in the early 1970s. Although different organisations used different labels--Lifelong Learning, recurrent education, education permanente--they all emphasised that learning is a lifelong process and that all education should be organised…

  15. Lifelong Education: A Stocktaking. UIE Monographs, 8.

    ERIC Educational Resources Information Center

    Cropley, A. J., Ed.; And Others

    Seven internationally known educators were asked to assess lifelong learning especially in relation to lifelong education and (1) revision of educational thinking and (2) educational practice. The authors addressed several key questions on lifelong education: For and by whom? Of and for what? How can it be achieved? The editor's overview and…

  16. The Routledge International Handbook of Lifelong Learning

    ERIC Educational Resources Information Center

    Jarvis, Peter, Ed.

    2010-01-01

    As lifelong learning grows in popularity, few comprehensive pictures of the phenomenon have emerged. The "Routledge International Handbook of Lifelong Learning" provides a disciplined and complete overview of lifelong learning internationally. The theoretical structure puts the learner at the centre and the book emanates from there,…

  17. The Routledge International Handbook of Lifelong Learning

    ERIC Educational Resources Information Center

    Jarvis, Peter, Ed.

    2010-01-01

    As lifelong learning grows in popularity, few comprehensive pictures of the phenomenon have emerged. The "Routledge International Handbook of Lifelong Learning" provides a disciplined and complete overview of lifelong learning internationally. The theoretical structure puts the learner at the centre and the book emanates from there,…

  18. Lifelong Learning--A Public Library Perspective.

    ERIC Educational Resources Information Center

    Kahlert, Maureen

    This paper presents a public library perspective on lifelong learning. The first section discusses the lifelong learning challenge, including the aims of the Australian National Marketing Strategy for Skills and Lifelong Learning, and findings of a national survey related to the value of and barriers to learning. The second section addresses the…

  19. Lifelong Learning: Policies, Practices, and Programs.

    ERIC Educational Resources Information Center

    Hatton, Michael J., Ed.

    The 26 articles in this book focus on lifelong learning policies, practices, and programs in 13 Asia Pacific countries. The following papers are included: "Half a Revolution: A Brief Survey of Lifelong Learning in New Zealand" (P. Methven and J. Hansen); "HRD in a Multicultural Workplace: The Need for Lifelong Learning" (M.…

  20. Lifelong Learning Policies, Paradoxes and Possibilities

    ERIC Educational Resources Information Center

    Tett, Lyn

    2014-01-01

    This paper argues that there are many ways of conceptualising lifelong learning and examines EU and Scottish lifelong learning policies in order to identify their underlying assumptions. Through an analysis of these policies, it is demonstrated that they draw on a number of inter-related fallacies that prioritise lifelong learning mainly in…

  1. Theoretical Analysis of Canadian Lifelong Education Development

    ERIC Educational Resources Information Center

    Mukan, Natalia; Barabash, Olena; Busko, Maria

    2014-01-01

    In the article, the problem of Canadian lifelong education development has been studied. The main objectives of the article are defined as theoretical analysis of scientific and pedagogical literature which highlights different aspects of the research problem; periods of lifelong education development; and determination of lifelong learning role…

  2. Towards a Conceptual Understanding of Lifelong Learning.

    ERIC Educational Resources Information Center

    McCannon, Roger S.

    Despite the lengthy existence of the concept of lifelong learning, there is still no one generally accepted theory of education as a lifelong process. More than an extension of adult education, lifelong learning rests on the belief that learning occurs throughout life, in different ways and through different processes. The key notion in lifelong…

  3. Theoretical Analysis of Canadian Lifelong Education Development

    ERIC Educational Resources Information Center

    Mukan, Natalia; Barabash, Olena; Busko, Maria

    2014-01-01

    In the article, the problem of Canadian lifelong education development has been studied. The main objectives of the article are defined as theoretical analysis of scientific and pedagogical literature which highlights different aspects of the research problem; periods of lifelong education development; and determination of lifelong learning role…

  4. Lifelong Learning: Policies, Practices, and Programs.

    ERIC Educational Resources Information Center

    Hatton, Michael J., Ed.

    The 26 articles in this book focus on lifelong learning policies, practices, and programs in 13 Asia Pacific countries. The following papers are included: "Half a Revolution: A Brief Survey of Lifelong Learning in New Zealand" (P. Methven and J. Hansen); "HRD in a Multicultural Workplace: The Need for Lifelong Learning" (M.…

  5. Evaluation of an alternating-calorie diet with and without exercise in the treatment of obesity.

    PubMed

    Hill, J O; Schlundt, D G; Sbrocco, T; Sharp, T; Pope-Cordle, J; Stetson, B; Kaler, M; Heim, C

    1989-08-01

    This study examined the effects of calorie alternation and exercise on weight loss. Moderately obese women (130-160% of ideal body weight) were randomly assigned to an alternating- or constant-calorie diet with or without aerobic exercise. Both diets provided an average of 1200 kcal/d over a 12-wk period; daily intake of subjects in the alternating-diet condition varied in a prescribed pattern from 600 to 1800 kcal/d. Exercising subjects walked 5 d/wk. All subjects participated in an intensive outpatient behavior-modification program. At the end of the study, exercised subjects had greater reductions in body weight and body fat percentage than did nonexercised subjects. The type of caloric restriction did not affect weight or fat loss. Changes in resting metabolic rate did not differ among groups. Alternating calories was neither beneficial nor detrimental as a weight-loss strategy whereas exercise was clearly beneficial in weight-loss therapy.

  6. Oral calorie supplements for cystic fibrosis.

    PubMed

    Smyth, Rosalind L; Walters, Sarah

    2012-10-17

    Poor nutrition occurs frequently in people with cystic fibrosis (CF) and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. To establish whether in people with CF, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane CF Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 19 July 2012. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with CF. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants. There were no significant differences between people receiving supplements or dietary advice alone for change in weight, height, body mass index, z score or other indices of nutrition or growth. Changes in weight (kg) at three, six and twelve months respectively were: MD 0.32 (95% CI -0.09 to 0.72); MD 0.47 (95% CI -0.07 to 1.02 ); and MD 0.16 (-0.68 to 1.00). Total calorie intake was greater in people taking supplements at 12 months, MD 265.70 (95% CI 42.94 to 488.46). There were no significant differences between the groups for anthropometric measures of body composition, lung function

  7. The pathophysiology of lifelong premature ejaculation

    PubMed Central

    2016-01-01

    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  8. The pathophysiology of lifelong premature ejaculation.

    PubMed

    Waldinger, Marcel D

    2016-08-01

    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  9. Lifelong learning in nursing: a Delphi study.

    PubMed

    Davis, Lisa; Taylor, Heidi; Reyes, Helen

    2014-03-01

    In order to foster a culture of lifelong learning in nursing, it is important to identify what the concept means in the nursing profession as well as the characteristics of a lifelong learner. The purpose of this Delphi study was to conceptualize lifelong learning from the perspective of nursing, and to identify characteristics and essential elements of lifelong learning. A Delphi Study technique in three phases was completed using an online survey tool. Data were analyzed for conceptual description, ratings of characteristics and attributes, and expert consensus in these three phases. An online survey tool was used in this study. Recognized experts in nursing education, administration and public policy participated in this study. Lifelong learning in nursing is defined as a dynamic process, which encompasses both personal and professional life. This learning process is also both formal and informal. Lifelong learning involves seeking and appreciating new worlds or ideas in order to gain a new perspective as well as questioning one's environment, knowledge, skills and interactions. The most essential characteristics of a lifelong learner are reflection, questioning, enjoying learning, understanding the dynamic nature of knowledge, and engaging in learning by actively seeking learning opportunities. Keeping the mind active is essential to both lifelong learning and being able to translate knowledge into the capacity to deliver high quality nursing care. It is hoped that a clearer understanding of lifelong learning in nursing will foster more discussion and research about intentional, active inclusion of lifelong learning behaviors in nursing curricula. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Testing food-related inhibitory control to high- and low-calorie food stimuli: Electrophysiological responses to high-calorie food stimuli predict calorie and carbohydrate intake.

    PubMed

    Carbine, Kaylie A; Christensen, Edward; LeCheminant, James D; Bailey, Bruce W; Tucker, Larry A; Larson, Michael J

    2017-07-01

    Maintaining a healthy diet has important implications for physical and mental health. One factor that may influence diet and food consumption is inhibitory control-the ability to withhold a dominant response in order to correctly respond to environmental demands. We examined how N2 amplitude, an ERP that reflects inhibitory control processes, differed toward high- and low-calorie food stimuli and related to food intake. A total of 159 participants (81 female; M age = 23.5 years; SD = 7.6) completed two food-based go/no-go tasks (one with high-calorie and one with low-calorie food pictures as no-go stimuli) while N2 amplitude was recorded. Participants recorded food intake using the Automated Self-Administered 24-hour Dietary Recall system. Inhibiting responses toward high-calorie stimuli elicited a larger (i.e., more negative) no-go N2 amplitude; inhibiting responses toward low-calorie stimuli elicited a smaller no-go N2 amplitude. Participants were more accurate during the high-calorie than low-calorie task, but took longer to respond on go trials toward high-calorie rather than low-calorie stimuli. When controlling for age, gender, and BMI, larger high-calorie N2 difference amplitude predicted lower caloric intake (β = 0.17); low-calorie N2 difference amplitude was not related to caloric intake (β = -0.03). Exploratory analyses revealed larger high-calorie N2 difference amplitude predicted carbohydrate intake (β = 0.22), but not protein (β = 0.08) or fat (β = 0.11) intake. Results suggest that withholding responses from high-calorie foods requires increased recruitment of inhibitory control processes, which may be necessary to regulate food consumption, particularly for foods high in calories and carbohydrates. © 2017 Society for Psychophysiological Research.

  11. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer ... to learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. This ...

  12. Modeling potential effects of reduced calories in kids' meals with toy giveaways.

    PubMed

    Freij, Maysoun Y; Sell, Randall L; Bozack, Anne K; Weiss, Linda J; Garcia, Ana C

    2014-02-01

    Given the large proportion of daily calories attributable to fast food, there is growing interest in considering whether ordinances that restrict calories in kids' meals with toy giveaways could avert weight gain among children. Based upon a literature review and stakeholder feedback, a model was developed to estimate the potential number of children that could be affected by a statewide toy giveaway ordinance and the caloric savings should such a policy effectively reduce the number of calories in kids' meals with toy giveaways. Assumptions included the estimated number of children that eat fast food each day, the proportion that choose a kids' meal with a toy, the caloric savings of a kids' meal that meets nutrition standards, and the degree to which these savings could result in weight gain averted per child per year. Using New York as a case study, the model estimates that, on a typical day, 5% (163,571) of children 0-12 years of age in New York could be affected by a toy ordinance. A child who typically consumes fast food two times per week could avoid gaining approximately 2 pounds per year with an ordinance requiring kids' meals to be ≤550 calories. The amount of weight gain averted would vary according to the calorie limit set by the law and the frequency of consumption per week. Our model indicates that a reduction in calories in kids' meals with toy giveaways has the potential to positively affect weight gain in a considerable percentage of children. Limitations of the model are considered.

  13. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    PubMed

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  14. Identifying Protein-Calorie Malnutrition Workshop.

    ERIC Educational Resources Information Center

    Walker, Susan S.; Barker, Ellen M.

    Instructional materials are provided for a workshop to enable participants to assist in identifying patients at risk with protein-calorie malnutrition and in corrrecting this nutritional deficiency. Representative topics are nutrients; protein, mineral, and vitamin sources, functions, and deficiency symptoms; malnutrition; nutritional deficiency…

  15. Northeastern Quadrant of the Caloris Basin

    NASA Image and Video Library

    2000-01-14

    This image, from NASA Mariner 10 spacecraft which launched in 1974, is of the northeastern quadrant of the Caloris basin and shows the smooth hills and domes between the inner and outer scarps and the well-developed radial system east of the outer scarp

  16. Identifying Protein-Calorie Malnutrition Workshop.

    ERIC Educational Resources Information Center

    Walker, Susan S.; Barker, Ellen M.

    Instructional materials are provided for a workshop to enable participants to assist in identifying patients at risk with protein-calorie malnutrition and in corrrecting this nutritional deficiency. Representative topics are nutrients; protein, mineral, and vitamin sources, functions, and deficiency symptoms; malnutrition; nutritional deficiency…

  17. Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise.

    PubMed

    Valdez, Gregorio; Tapia, Juan C; Kang, Hyuno; Clemenson, Gregory D; Gage, F H; Lichtman, Jeff W; Sanes, Joshua R

    2010-08-17

    The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.

  18. Oral calorie supplements for cystic fibrosis.

    PubMed

    Smyth, Rosalind L; Rayner, Oli

    2017-05-04

    Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review. To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were

  19. Mentoring is a Lifelong Activity

    NASA Astrophysics Data System (ADS)

    Hamilton, Joseph

    2016-09-01

    One of the greatest personal benefits of mentoring and working with graduate students and postdoctoral fellows is the life-long journey together. Having graduate students who keep up with you, ask advice and sometimes get it when they haven't asked for it, being able to help them find a job, and in some cases, continuing to do research together for over 50 years is a real gift. Seeing the success of your students in their own research programs, or as Professors, or in industry, makes me feel proud like I do in my children, and when we gather at conferences, it does seem like a family.

  20. Embodied crop calories in animal products

    NASA Astrophysics Data System (ADS)

    Pradhan, Prajal; Lüdeke, Matthias K. B.; Reusser, Dominik E.; Kropp, Jürgen P.

    2013-12-01

    Increases in animal products consumption and the associated environmental consequences have been a matter of scientific debate for decades. Consequences of such increases include rises in greenhouse gas emissions, growth of consumptive water use, and perturbation of global nutrients cycles. These consequences vary spatially depending on livestock types, their densities and their production system. In this letter, we investigate the spatial distribution of embodied crop calories in animal products. On a global scale, about 40% of the global crop calories are used as livestock feed (we refer to this ratio as crop balance for livestock) and about 4 kcal of crop products are used to generate 1 kcal of animal products (embodied crop calories of around 4). However, these values vary greatly around the world. In some regions, more than 100% of the crops produced is required to feed livestock requiring national or international trade to meet the deficit in livestock feed. Embodied crop calories vary between less than 1 for 20% of the livestock raising areas worldwide and greater than 10 for another 20% of the regions. Low values of embodied crop calories are related to production systems for ruminants based on fodder and forage, while large values are usually associated with production systems for non-ruminants fed on crop products. Additionally, we project the future feed demand considering three scenarios: (a) population growth, (b) population growth and changes in human dietary patterns and (c) changes in population, dietary patterns and feed conversion efficiency. When considering dietary changes, we project the global feed demand to be almost doubled (1.8-2.3 times) by 2050 compared to 2000, which would force us to produce almost equal or even more crops to raise our livestock than to directly nourish ourselves in the future. Feed demand is expected to increase over proportionally in Africa, South-Eastern Asia and Southern Asia, putting additional stress on these

  1. Stricter School Soda Limits Offered: Facing Lawsuit Threat, Beverage Industry Vows to Curb High-Calorie Drinks

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2006-01-01

    The soft-drink industry vowed to voluntarily curb selling sugary sodas and other high-calorie beverages in schools, a move that was taken under threat of litigation by critics who see the industry as a prime culprit in a national obesity crisis. The promise offered no guarantee that schools would go along with the restrictions, though many…

  2. Stricter School Soda Limits Offered: Facing Lawsuit Threat, Beverage Industry Vows to Curb High-Calorie Drinks

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2006-01-01

    The soft-drink industry vowed to voluntarily curb selling sugary sodas and other high-calorie beverages in schools, a move that was taken under threat of litigation by critics who see the industry as a prime culprit in a national obesity crisis. The promise offered no guarantee that schools would go along with the restrictions, though many…

  3. From Residency to Lifelong Learning.

    PubMed

    Brandt, Keith

    2015-11-01

    The residency training experience is the perfect environment for learning. The university/institution patient population provides a never-ending supply of patients with unique management challenges. Resources abound that allow the discovery of knowledge about similar situations. Senior teachers provide counseling and help direct appropriate care. Periodic testing and evaluations identify deficiencies, which can be corrected with future study. What happens, however, when the resident graduates? Do they possess all the knowledge they'll need for the rest of their career? Will medical discovery stand still limiting the need for future study? If initial certification establishes that the physician has the skills and knowledge to function as an independent physician and surgeon, how do we assure the public that plastic surgeons will practice lifelong learning and remain safe throughout their career? Enter Maintenance of Certification (MOC). In an ideal world, MOC would provide many of the same tools as residency training: identification of gaps in knowledge, resources to correct those deficiencies, overall assessment of knowledge, feedback about communication skills and professionalism, and methods to evaluate and improve one's practice. This article discusses the need; for education and self-assessment that extends beyond residency training and a commitment to lifelong learning. The American Board of Plastic Surgery MOC program is described to demonstrate how it helps the diplomate reach the goal of continuous practice improvement.

  4. Oral calorie supplements for cystic fibrosis.

    PubMed

    Smyth, Rosalind L; Rayner, Oli

    2014-11-03

    Poor nutrition occurs frequently in people with cystic fibrosis (CF) and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. To establish whether in people with CF, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane CF Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 03 July 2014. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with CF. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were concerns surrounding allocation concealment. There were no significant differences between

  5. Metabolomics Insights into the Modulatory Effects of Long-Term Low Calorie Intake in Mice.

    PubMed

    Wu, Junfang; Yang, Liu; Li, Shoufeng; Huang, Ping; Liu, Yong; Wang, Yulan; Tang, Huiru

    2016-07-01

    There is increasing evidence that calorie restriction without malnutrition can extend longevity and delay the onset of age-associated disorders. Identifying the biochemical perturbations associated with different dietary habits would provide valuable insights into associations between metabolism and longevity. To reveal the effects of long-term dietary interventions on metabolic perturbations, we investigated serum and urinary metabolic changes induced by interactive high/low fat diet in combination with/without reduced caloric intake over a life span in mice using NMR-based metabonomics. We found that the high calorie dietary regime disturbed lipid metabolism, suppressed glycolysis and TCA cycles, stimulated oxidative stress, promoted nucleotide metabolism and gluconeogenesis, and perturbed gut microbiota-host interactions. Such changes could be modified by long-term low calorie intake. Most importantly, we found that the calorie intake index exerts a dominant effect on metabolic perturbations irrespective of dietary regime. Our investigation provides a holistic view of the metabolic impact of long-term dietary interventions, which are important for detecting physiological changes and dietary effects on mammalian metabolism.

  6. High-calorie food-cues impair working memory performance in high and low food cravers.

    PubMed

    Meule, Adrian; Skirde, Ann Kathrin; Freund, Rebecca; Vögele, Claus; Kübler, Andrea

    2012-10-01

    The experience of food craving can lead to cognitive impairments. Experimentally induced chocolate craving exhausts cognitive resources and, therefore, impacts working memory, particularly in trait chocolate cravers. In the current study, we investigated the effects of exposure to food-cues on working memory task performance in a group with frequent and intense (high cravers, n=28) and less pronounced food cravings (low cravers, n=28). Participants performed an n-back task that contained either pictures of high-calorie sweets, high-calorie savory foods, or neutral objects. Current subjective food craving was assessed before and after the task. All participants showed slower reaction times and made more omission errors in response to food-cues, particularly savory foods. There were no differences in task performance between groups. State cravings did not differ between groups before the task, but increased more in high cravers compared to low cravers during the task. Results support findings about food cravings impairing visuo-spatial working memory performance independent of trait cravings. They further show that this influence is not restricted to chocolate, but also applies to high-calorie savory foods. Limiting working memory capacity may be especially crucial in persons who are more prone to high-calorie food-cues and experience such cravings habitually.

  7. Lifelong Learning in Action: Hong Kong Practitioners' Perspectives.

    ERIC Educational Resources Information Center

    Cribbin, John, Ed.; Kennedy, Peter, Ed.

    This document consists of 32 papers presenting Hong Kong practitioners' perspectives on lifelong learning. The following papers are included: "Lifelong Learning" (Albert Tuijnman); "Growth and Development of Lifelong Learning in Hong Kong " (John Cribbin); "Competition and Collaboration" (John Cribbin); "A…

  8. Lifelong Learning in Action: Hong Kong Practitioners' Perspectives.

    ERIC Educational Resources Information Center

    Cribbin, John, Ed.; Kennedy, Peter, Ed.

    This document consists of 32 papers presenting Hong Kong practitioners' perspectives on lifelong learning. The following papers are included: "Lifelong Learning" (Albert Tuijnman); "Growth and Development of Lifelong Learning in Hong Kong " (John Cribbin); "Competition and Collaboration" (John Cribbin); "A…

  9. Two Wheels for Lifelong Learning in Korea: Credit Banking & Multimedia Technology.

    ERIC Educational Resources Information Center

    Pak, Min Sun

    Despite Korea's current emphasis on college entrance exams and formal education, the lifelong learning paradigm adhered to in the past can be re-established with the development of credit banking and multimedia technology. Due to restricted participation in higher education, a university degree has become a ticket to the social elite, with…

  10. Candlestick and Faces: Aspects of Lifelong Learning.

    ERIC Educational Resources Information Center

    Hunt, Cheryl

    1999-01-01

    Government policies view lifelong learning in terms of economic development. A SWOT (strengths, weaknesses, opportunities, threats) analysis of the environment of British community education councils revealed other views of lifelong learning: it takes time and political expediency and national policy can adversely affect what and how people learn.…

  11. Social Software for Life-Long Learning

    ERIC Educational Resources Information Center

    Klamma, Ralf; Chatti, Mohamed Amine; Duval, Erik; Hummel, Hans; Hvannberg, Ebba Thora; Kravcik, Milos; Law, Effie; Naeve, Ambjorn; Scott, Peter

    2007-01-01

    Life-long learning is a key issue for our knowledge society. With social software systems new heterogeneous kinds of technology enhanced informal learning are now available to the life-long learner. Learners outside of learning institutions now have access to powerful social communities of experts and peers who are together forging a new web 2.0.…

  12. The Nordic Model of Lifelong Learning

    ERIC Educational Resources Information Center

    Rubenson, Kjell

    2006-01-01

    This article explores how the so called Nordic welfare state, with its specific institutional make up, handles Lifelong Learning in a time characterised by the challenges of economic globalisation and the hegemonic impact of the neo-liberal agenda. The analysis reveals a high participation in the Nordic countries in Lifelong Learning and, in…

  13. Economics and Finance of Lifelong Learning.

    ERIC Educational Resources Information Center

    Verry, Donald

    This book represents one result of the international conference on "Lifelong Learning as an Affordable Investment," held December 6-8, 2000 in Ottawa, Canada. It examines the economic and financial issues that arise in implementing lifelong learning and considers how the public and private sectors are actually addressing or might address…

  14. WTO and Lifelong Education Strategies for Teachers

    ERIC Educational Resources Information Center

    Wang, Zhi-guo; Zheng, Yu

    2006-01-01

    After China's entry into the World Trade Organization (WTO), teachers have been confronted with many opportunities and challenges. Lifelong education strategies are problems we should take into account carefully. This article expounds the objective demands, ideas, content, measures and functions of lifelong education.

  15. Where's the Learning in Lifelong Participation?

    ERIC Educational Resources Information Center

    Williams, Joanna

    2012-01-01

    This article provides a retrospective review and analysis of New Labour's policies in relation to lifelong learning. New Labour's plans to promote social inclusion through lifelong learning resulted in a focus upon participation in terms of increasing the numbers of students involved in formal learning and increasing their participation in…

  16. A Design Model for Lifelong Learning Networks

    ERIC Educational Resources Information Center

    Koper, Rob; Giesbers, Bas; van Rosmalen, Peter; Sloep, Peter; van Bruggen, Jan; Tattersall, Colin; Vogten, Hubert; Brouns, Francis

    2005-01-01

    The provision of lifelong learning facilities is considered to be a major new direction for higher and distance teaching educational institutes catering for the demands of industry and society. ICT networks will in future support seamless, ubiquitous access to lifelong learning facilities at home, at work, in schools and universities. This implies…

  17. A Critical Look at Lifelong Learning

    ERIC Educational Resources Information Center

    Kaya, H. Eylem

    2014-01-01

    Education, which is a fundamental right of human being, has been transformed into a kind of lifelong prisoning by marketing step by step under the name of lifelong learning. Adult education as one of the most crucial parts of the educational system has also been affected by the global trend of an international actor, the European Union through its…

  18. A National Strategy for Lifelong Learning.

    ERIC Educational Resources Information Center

    Coffield, Frank, Ed.

    The first paper of this set of 12 conference papers, "Nine Learning Fallacies and Their Replacement by a National Strategy for Lifelong Learning," by Frank Coffield, synthesizes the opinions of other participants, and goes beyond them to set forth an outline of a strategy for lifelong learning in the United Kingdom. Following this…

  19. Lifelong Learning and the Absence of Gender

    ERIC Educational Resources Information Center

    Rogers, Alan

    2006-01-01

    This paper identifies that (with very few exceptions) in most of current literature on lifelong learning, gender issues are ignored or overlooked. An extensive review of the literature demonstrates this neglect. Some reasons are given for this, including the fact that most analyses of lifelong learning tend to stress the individual learning…

  20. Lifelong Career Development for Handicapped Individuals.

    ERIC Educational Resources Information Center

    Brolin, Donn E.; Carver, James T.

    Designed for individuals interested in implementing career development programs for disabled adults, this report presents information on the Lifelong Career Development (LCD) project and its potential for implementation in the community college. Chapter 1 examines lifelong learning and the career development needs of disabled individuals, presents…

  1. Lifelong Learning: A Pacification of "Know How"

    ERIC Educational Resources Information Center

    Nicoll, Katherine; Fejes, Andreas

    2011-01-01

    A tendency of previous studies of lifelong learning to focus on learning and learning subjectivities may have led to an underestimation of potential effects in terms of a system of knowledge constitutive processes that operates powerfully to shape our societies. In this paper we explore lifelong learning and practices in the construction of…

  2. Social Software for Life-Long Learning

    ERIC Educational Resources Information Center

    Klamma, Ralf; Chatti, Mohamed Amine; Duval, Erik; Hummel, Hans; Hvannberg, Ebba Thora; Kravcik, Milos; Law, Effie; Naeve, Ambjorn; Scott, Peter

    2007-01-01

    Life-long learning is a key issue for our knowledge society. With social software systems new heterogeneous kinds of technology enhanced informal learning are now available to the life-long learner. Learners outside of learning institutions now have access to powerful social communities of experts and peers who are together forging a new web 2.0.…

  3. Lifelong Learning Policy in Two National Contexts

    ERIC Educational Resources Information Center

    Rasmussen, Palle

    2014-01-01

    This article describes and discusses the development of lifelong learning policy in two EU member states, Denmark and Portugal. The purpose is to show how different societal and historical contexts shape the development and implementation of lifelong learning policies, even though these policies have significant common elements. As a basis for the…

  4. A Critical Look at Lifelong Learning

    ERIC Educational Resources Information Center

    Kaya, H. Eylem

    2014-01-01

    Education, which is a fundamental right of human being, has been transformed into a kind of lifelong prisoning by marketing step by step under the name of lifelong learning. Adult education as one of the most crucial parts of the educational system has also been affected by the global trend of an international actor, the European Union through its…

  5. Supporting Lifelong Learning in the Information Age

    ERIC Educational Resources Information Center

    Zhou, Wei; Yasuda, Takami; Yokoi, Shigeki

    2007-01-01

    Many countries are considering lifelong learning, which is becoming an important education goal, and promoting lifelong learning in the information age. With the development of Information and Communications Technology (ICT), digital divides have become a major concern in the world. In this study, we focus on three dimensions of digital divides in…

  6. Lifelong Learning: A Pacification of "Know How"

    ERIC Educational Resources Information Center

    Nicoll, Katherine; Fejes, Andreas

    2011-01-01

    A tendency of previous studies of lifelong learning to focus on learning and learning subjectivities may have led to an underestimation of potential effects in terms of a system of knowledge constitutive processes that operates powerfully to shape our societies. In this paper we explore lifelong learning and practices in the construction of…

  7. Researching the Rhetoric of Lifelong Learning.

    ERIC Educational Resources Information Center

    Edwards, Richard; Nicoll, Katherine

    2001-01-01

    In the analysis of lifelong-learning policies, the gap between rhetoric and reality has been avidly debated. Such critiques are misguided; an "exemplary" rhetorical analysis of lifelong-learning policy is possible. UK government publications suggest that rhetorical analysis helps identify the politics of discourse involved in…

  8. Lifelong Learning and Demographics: A Japanese Perspective

    ERIC Educational Resources Information Center

    Ogawa, Seiko

    2005-01-01

    This paper explores the social dimension of lifelong learning from the perspective of demographics, with particular focus on the issue of the birth of fewer children, which has become one of the most important current social issues in Japanese society. When considering the relationship between lifelong learning and demographics, the issues arising…

  9. The Nordic Model of Lifelong Learning

    ERIC Educational Resources Information Center

    Rubenson, Kjell

    2006-01-01

    This article explores how the so called Nordic welfare state, with its specific institutional make up, handles Lifelong Learning in a time characterised by the challenges of economic globalisation and the hegemonic impact of the neo-liberal agenda. The analysis reveals a high participation in the Nordic countries in Lifelong Learning and, in…

  10. Lifelong Learning Policy in Two National Contexts

    ERIC Educational Resources Information Center

    Rasmussen, Palle

    2014-01-01

    This article describes and discusses the development of lifelong learning policy in two EU member states, Denmark and Portugal. The purpose is to show how different societal and historical contexts shape the development and implementation of lifelong learning policies, even though these policies have significant common elements. As a basis for the…

  11. Policy on Lifelong Learning in Australia

    ERIC Educational Resources Information Center

    Chapman, Judith; Gaff, Janet; Toomey, Ron; Aspin, David

    2005-01-01

    This paper provides an account of the extent to which the concept of lifelong learning has been incorporated into the education policies of the Australian Commonwealth and State Governments and the Catholic and Independent schooling sectors, taking particular note of the application of lifelong learning to policies pertaining to teacher education.

  12. Recent Developments in Japan's Lifelong Learning Society.

    ERIC Educational Resources Information Center

    Makino, Atsushi

    In the wake of economic and social change in Japan, several lifelong learning initiatives have been implemented. Structural changes such as internationalization, the coming of the information age, and the maturation of Japanese society caused the formerly homogeneous society to become more flexible, paving the way for lifelong learning. Additional…

  13. Toward a Model of Lifelong Education.

    ERIC Educational Resources Information Center

    Knowles, Malcolm S.

    Some of the criticisms that have been leveled at the educational establishment by social analysts are discussed. It is suggested that one of the new realities is that education must be a lifelong process in order to avoid the catastrophe of human obsolescence. The assumptions and elements for a new model of education as a lifelong process are…

  14. Lifelong Learning and Demographics: A Japanese Perspective

    ERIC Educational Resources Information Center

    Ogawa, Seiko

    2005-01-01

    This paper explores the social dimension of lifelong learning from the perspective of demographics, with particular focus on the issue of the birth of fewer children, which has become one of the most important current social issues in Japanese society. When considering the relationship between lifelong learning and demographics, the issues arising…

  15. Effect of aging and dietary restriction on DNA repair

    SciTech Connect

    Weraarchakul, N.; Strong, R.; Wood, W.G.; Richardson, A.

    1989-03-01

    DNA repair was studied as a function of age in cells isolated from both the liver and the kidney of male Fischer F344 rats. DNA repair was measured by quantifying unscheduled DNA synthesis induced by UV irradiation. Unscheduled DNA synthesis decreased approximately 50% between the ages of 5 and 30 months in both hepatocytes and kidney cells. The age-related decline in unscheduled DNA synthesis in cells isolated from the liver and kidney was compared in rats fed ad libitum and rats fed a calorie-restricted diet; calorie restriction has been shown to increase the survival of rodents. The level of unscheduled DNA synthesis was significantly higher in hepatocytes and kidney cells isolated from the rats fed the restricted diet. Thus, calorie restriction appears to retard the age-related decline in DNA repair.

  16. A randomized trial of calorie labeling on menus.

    PubMed

    Hammond, David; Goodman, Samantha; Hanning, Rhona; Daniel, Samantha

    2013-12-01

    Food consumed outside the home accounts for a growing proportion of the North American diet and has been associated with increased obesity. To examine the effect of nutrition labeling on menus on awareness, use, and food consumption, including the impact of "traffic light" labeling and adding other nutrients. Blinded, randomized trial with 635 Canadian adults conducted in 2010-2011. Participants ordered a free meal from one of four experimental menus: 1) no nutritional information shown, 2) calorie amounts only, 3) calorie amounts in "traffic lights", and 4) calorie, fat, sodium, and sugar shown in "traffic lights". Recall of nutrition information, knowledge of calorie content and nutrient consumption were assessed. Participants in the calorie conditions were more likely to recall the calorie content of meals and to report using nutrition information when ordering. The calorie content of meals was not significantly different across conditions; however, calorie consumption was significantly lower among participants in the Calorie-only condition compared to the No information condition (mean=-96 kcal, p=.048). Menu labeling increased awareness and use of nutrition information and reduced consumption. Adding "traffic lights", fat, sodium, and sugar amounts to menus had little impact compared to calorie-only labeling. © 2013.

  17. Influence of calorie reduction on DNA repair capacity of human peripheral blood mononuclear cells.

    PubMed

    Matt, Katja; Burger, Katharina; Gebhard, Daniel; Bergemann, Jörg

    2016-03-01

    Caloric restrictive feeding prolongs the lifespan of a variety of model organisms like rodents and invertebrates. It has been shown that caloric restriction reduces age-related as well as overall-mortality, reduces oxidative stress and influences DNA repair ability positively. There are numerous studies underlining this, but fewer studies involving humans exist. To contribute to a better understanding of the correlation of calorie reduction and DNA repair in humans, we adapted the host cell reactivation assay to an application with human peripheral blood mononuclear cells. Furthermore, we used this reliable and reproducible assay to research the influence of a special kind of calorie reduction, namely F. X. Mayr therapy, on DNA repair capacity. We found a positive effect in all persons with low pre-existing DNA repair capacity. In individuals with normal pre-existing DNA repair capacity, no effect on DNA repair capacity was detectable. Decline of DNA repair, accumulation of oxidative DNA damages, mitochondrial dysfunction, telomere shortening as well as caloric intake are widely thought to contribute to aging. With regard to that, our results can be considered as a strong indication that calorie reduction may support DNA repair processes and thus contribute to a healthier aging.

  18. Lifelong learning: fostering a culture of curiosity.

    PubMed

    Eason, Toni

    2010-01-01

    Lifelong learning contributes to the development of knowledge and skill in nursing. A focus on continuous learning is necessary to remain current on trends, practices, and the newest treatments in the field of nursing. Creation of a culture where educational growth is supported and promoted is vital to advancement of the nursing profession. Nurses' satisfaction with their professional role can be further enhanced by demonstrated expertise through lifelong learning. Expertise in nursing is solidly founded on evidence-based practice. Research, education, and experience in nursing practice are linked to evidence-based practice and lifelong learning; both are essential to remaining well versed in health care service delivery.

  19. Empirical evaluation of the ability to learn a calorie counting system and estimate portion size and food intake.

    PubMed

    Martin, Corby K; Anton, Stephen D; York-Crowe, Emily; Heilbronn, Leonie K; VanSkiver, Claudia; Redman, Leanne M; Greenway, Frank L; Ravussin, Eric; Williamson, Donald A

    2007-08-01

    The aim of this study was to determine if: (1) participants could learn the HMR Calorie System by testing if their use of the system was more accurate after training; and (2) estimated portion size and food intake improved with training. A secondary aim was to use PACE (photographic assessment of calorie estimation) to assess if participants learned the HMR system. The PACE consists of pictures of foods, the energy content of which is known. A within-subjects design was used to test the aims of this study. Participants were 44 overweight (25 calorie restriction groups or a weight maintenance group for 6 months. Participants attended weekly sessions and were trained to use the HMR system from weeks 5 to 8. Participants were provided with foods to test if they could effectively use the HMR system and accurately estimate portion size and the amount of food eaten. The PACE was also used to quantify accuracy at using the HMR system. Training resulted in more accurate estimation of food intake, use of the HMR system and estimated portion size when presented with food. Additionally, training resulted in significantly more accurate use of the HMR system when measured with PACE. It is concluded that people can learn the HMR Calorie System and improve the accuracy of portion size and food intake estimates. The PACE is a useful assessment tool to test if participants learn a calorie counting system.

  20. Do calories or osmolality determine gastric emptying

    SciTech Connect

    Shafer, R.B.; Levine, A.S.; Marlette, J.M.; Morley, J.E.

    1984-01-01

    Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) and gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals.

  1. Reading Policy Texts: Lifelong Leaning as Metaphor.

    ERIC Educational Resources Information Center

    Nicoll, Katherine; Edwards, Richard

    2000-01-01

    Argues the necessity of a discursive approach to policy analysis. Emphasizes the importance of metaphor to the analysis. Explores the metaphorical role of lifelong learning in educational policy. (SK)

  2. Experimental approaches to nutrition and cancer: fats, calories, vitamins and minerals.

    PubMed

    Good, R A; Lorenz, E; Engelman, R; Day, N K

    1990-01-01

    Chronic energy intake restriction (CEIR) inhibits lymphoproliferative disease, autoimmune-based renal disease and mammary adenocarcinoma in mice of numerous short-lived strains (MRL/lpr, C3H/Bi, C3H/Ou). Doubling and tripling of life span and health span and inhibition of development of diseases associated with aging could be attributed to restriction of calories but not to restriction of dietary fat in the absence of calorie restriction. In mice of both long- and short-lived strains, CEIR dramatically prevents the waning of immunologic vigor that commonly occurs with aging, delays thymic involution, impairs formation of circulating immune complexes, prevents the renal injury that accompanies autoimmune disease, and significantly forestalls development of genetically determined lymphoproliferative or neoplastic disease. Evidence suggests that CEIR may exert these beneficial influences in part through regulation of cellular proliferation. Trace elements, particularly zinc, as well as vitamins may play important roles in maintaining immunocompetence and also appear to be of significance in the dietary prevention of certain experimental cancers.

  3. "A calorie is a calorie" violates the second law of thermodynamics.

    PubMed

    Feinman, Richard D; Fine, Eugene J

    2004-07-28

    The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets--greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics.

  4. "A calorie is a calorie" violates the second law of thermodynamics

    PubMed Central

    Feinman, Richard D; Fine, Eugene J

    2004-01-01

    The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets – greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics. PMID:15282028

  5. Counting Calories: Resident Perspectives on Calorie Labeling in New York City

    ERIC Educational Resources Information Center

    Gordon, Cynthia; Hayes, Roger

    2012-01-01

    Objective: The present study investigates consumer responses to New York City's 2008 calorie labeling regulation in 2 lower-income neighborhoods of New York City. Methods: Focus groups were conducted, and 34 fast-food consumers participated. Group summaries and descriptive and analytic depictions of group responses and interactions were developed…

  6. Counting Calories: Resident Perspectives on Calorie Labeling in New York City

    ERIC Educational Resources Information Center

    Gordon, Cynthia; Hayes, Roger

    2012-01-01

    Objective: The present study investigates consumer responses to New York City's 2008 calorie labeling regulation in 2 lower-income neighborhoods of New York City. Methods: Focus groups were conducted, and 34 fast-food consumers participated. Group summaries and descriptive and analytic depictions of group responses and interactions were developed…

  7. Youth and Lifelong Education: After-School Programmes as a Vital Component of Lifelong Education Infrastructure

    ERIC Educational Resources Information Center

    Lauzon, Allan C.

    2013-01-01

    This paper argues that after-school programmes need to be considered an essential part of lifelong learning infrastructure, particularly in light of the dominance of the economic discourse in both lifelong learning literature and the initial schooling literature. The paper, which is based upon existing literature, begins by providing an overview…

  8. Youth and Lifelong Education: After-School Programmes as a Vital Component of Lifelong Education Infrastructure

    ERIC Educational Resources Information Center

    Lauzon, Allan C.

    2013-01-01

    This paper argues that after-school programmes need to be considered an essential part of lifelong learning infrastructure, particularly in light of the dominance of the economic discourse in both lifelong learning literature and the initial schooling literature. The paper, which is based upon existing literature, begins by providing an overview…

  9. Metabolic effects of very low calorie weight reduction diets.

    PubMed

    Hoffer, L J; Bistrian, B R; Young, V R; Blackburn, G L; Matthews, D E

    1984-03-01

    A randomized comparison trial of two very low calorie weight reduction diets was carried out for 5 or 8 wk in 17 healthy obese women. One diet provided 1.5 g protein/kg ideal body weight; the other provided 0.8 g protein/kg ideal body weight plus 0.7 g carbohydrate/kg ideal body weight. The diets were isocaloric (500 kcal). Amino acid metabolism was studied by means of tracer infusions of L-[1-13C]leucine and L-[15N]alanine. After 3 wk of adaptation to the diets, nitrogen balance was zero for the 1.5 g protein diet but -2 g N/d for the 0.8 g protein diet. Postabsorptive plasma leucine and alanine flux decreased from base line by an equal extent with both diets by approximately 20 and 40%, respectively. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted, and that nitrogen balance is improved by increasing the protein intake above that level. Basal rates of whole body nitrogen turnover are relatively well maintained, compared with total fasting, at both protein intakes. However, turnover in the peripheral compartment, as evidenced by alanine flux, may be markedly diminished with either diet.

  10. Quantifying Accurate Calorie Estimation Using the "Think Aloud" Method

    ERIC Educational Resources Information Center

    Holmstrup, Michael E.; Stearns-Bruening, Kay; Rozelle, Jeffrey

    2013-01-01

    Objective: Clients often have limited time in a nutrition education setting. An improved understanding of the strategies used to accurately estimate calories may help to identify areas of focused instruction to improve nutrition knowledge. Methods: A "Think Aloud" exercise was recorded during the estimation of calories in a standard dinner meal…

  11. Calorie Labeling, Fast Food Purchasing and Restaurant Visits

    PubMed Central

    Elbel, Brian; Mijanovich, Tod; Dixon, Beth; Abrams, Courtney; Weitzman, Beth; Kersh, Rogan; Auchincloss, Amy H.; Ogedegbe, Gbenga

    2013-01-01

    Objective Obesity is a pressing public health problem without proven population-wide solutions. Researchers sought to determine whether a city-mandated policy requiring calorie labeling at fast food restaurants was associated with consumer awareness of labels, calories purchased and fast food restaurant visits. Design and Methods Difference-in-differences design, with data collected from consumers outside fast food restaurants and via a random digit dial telephone survey, before (December 2009) and after (June 2010) labeling in Philadelphia (which implemented mandatory labeling) and Baltimore (matched comparison city). Measures included: self-reported use of calorie information, calories purchased determined via fast food receipts, and self-reported weekly fast-food visits. Results The consumer sample was predominantly Black (71%), and high school educated (62%). Post-labeling, 38% of Philadelphia consumers noticed the calorie labels for a 33 percentage point (p<.001) increase relative to Baltimore. Calories purchased and number of fast food visits did not change in either city over time. Conclusions While some consumer reports noticing and using calorie information, no population level changes were noted in calories purchased or fast food visits. Other controlled studies are needed to examine the longer term impact of labeling as it becomes national law. PMID:24136905

  12. Calorie labeling, fast food purchasing and restaurant visits.

    PubMed

    Elbel, Brian; Mijanovich, Tod; Dixon, L Beth; Abrams, Courtney; Weitzman, Beth; Kersh, Rogan; Auchincloss, Amy H; Ogedegbe, Gbenga

    2013-11-01

    Obesity is a pressing public health problem without proven population-wide solutions. Researchers sought to determine whether a city-mandated policy requiring calorie labeling at fast food restaurants was associated with consumer awareness of labels, calories purchased and fast food restaurant visits. Difference-in-differences design, with data collected from consumers outside fast food restaurants and via a random digit dial telephone survey, before (December 2009) and after (June 2010) labeling in Philadelphia (which implemented mandatory labeling) and Baltimore (matched comparison city). Measures included: self-reported use of calorie information, calories purchased determined via fast food receipts, and self-reported weekly fast-food visits. The consumer sample was predominantly Black (71%), and high school educated (62%). Postlabeling, 38% of Philadelphia consumers noticed the calorie labels for a 33% point (P < 0.001) increase relative to Baltimore. Calories purchased and number of fast food visits did not change in either city over time. While some consumers report noticing and using calorie information, no population level changes were noted in calories purchased or fast food visits. Other controlled studies are needed to examine the longer term impact of labeling as it becomes national law. Copyright © 2013 The Obesity Society.

  13. Quantifying Accurate Calorie Estimation Using the "Think Aloud" Method

    ERIC Educational Resources Information Center

    Holmstrup, Michael E.; Stearns-Bruening, Kay; Rozelle, Jeffrey

    2013-01-01

    Objective: Clients often have limited time in a nutrition education setting. An improved understanding of the strategies used to accurately estimate calories may help to identify areas of focused instruction to improve nutrition knowledge. Methods: A "Think Aloud" exercise was recorded during the estimation of calories in a standard dinner meal…

  14. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity

    PubMed Central

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-01-01

    Background/Objectives: The uroguanylin-GUCY2C gut–brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Subjects/Methods: Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ERT2-Rosa-STOPloxP/loxP-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. Results: DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. Conclusions: These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression

  15. Physical growth of cebus monkeys, Cebus albifrons, during protein or calorie deficiency.

    PubMed

    Fleagle, J G; Samonds, K W; Hegsted, D M

    1975-03-01

    Infant cebus monkey (Cebus albifrons) on experimental diets providing low-protein (2.8% of calories) or low-calorie (67% of ad libitum intake) levels for 20 weeks beginning at 8 weeks of age showed marked changes in their patterns of physical growth. Significant size differences between the malnourished animals and the control group appeared within 4 weeks. Although rates of growth were significantly reduced in all measurements, all of the malnourished monkeys, including low-protein animals showing zero weight gain, continued skeletal growth (except in skull measurements) at low levels for the duration of experiment. Both the protein- and calorie-restricted animals developed a thin, emaciated appearance often associated with marasmus, not by the continuous loss of tissue byt by the redistribution of the tissue over a slowly expanding skeleton. For many skeletal proportions, the pattern and shape development in the malnourished animals differed from that of the control animals. Growth during malnutrition was most affected in those parts of the skeleton which were more advanced in relative size.

  16. 21 CFR 101.60 - Nutrient content claims for the calorie content of foods.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... made on products that meet the criteria in § 101.60(b)(1) or (b)(2) for “calorie free” or “low calorie... vinegar, a calorie free food”). (2) The terms “low calorie,” “few calories,” “contains a small amount of... type and not merely to the particular brand to which the label attaches (e.g., “celery, a low calorie...

  17. 21 CFR 101.60 - Nutrient content claims for the calorie content of foods.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... made on products that meet the criteria in § 101.60(b)(1) or (b)(2) for “calorie free” or “low calorie... vinegar, a calorie free food”). (2) The terms “low calorie,” “few calories,” “contains a small amount of... type and not merely to the particular brand to which the label attaches (e.g., “celery, a low calorie...

  18. 21 CFR 101.60 - Nutrient content claims for the calorie content of foods.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... made on products that meet the criteria in § 101.60(b)(1) or (b)(2) for “calorie free” or “low calorie... vinegar, a calorie free food”). (2) The terms “low calorie,” “few calories,” “contains a small amount of... type and not merely to the particular brand to which the label attaches (e.g., “celery, a low calorie...

  19. 21 CFR 101.60 - Nutrient content claims for the calorie content of foods.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... made on products that meet the criteria in § 101.60(b)(1) or (b)(2) for “calorie free” or “low calorie... vinegar, a calorie free food”). (2) The terms “low calorie,” “few calories,” “contains a small amount of... type and not merely to the particular brand to which the label attaches (e.g., “celery, a low calorie...

  20. Point-of-Purchase Calorie Labeling Has Little Influence on Calories Ordered Regardless of Body Mass Index.

    PubMed

    Rendell, Sarah Litman; Swencionis, Charles

    2014-09-01

    The obesity epidemic has incited legislation aimed to inform consumers of the nutritional value of food items available in restaurants and fast food establishments, with the presumption that knowing the caloric content in a meal might enable patrons to make healthier choices when ordering. However, available research shows mixed results regarding consumers' use of calorie information to promote healthier purchases. The aim of this study was to determine whether menu type, specifically having viewed a menu with calorie disclosures or not, would have an impact on how many calories were in a lunch meal ordered by a patron. Additionally, we sought to identify body mass index (BMI) as a moderator of the relationship between viewing a menu with or without calorie information and the number of calories an individual orders for lunch. Two hundred forty-five adults participated in the study and completed the questionnaire. Results indicated neither menu type, nor reporting having seen calorie information, was significantly related to the number of calories in the foods that participants ordered, even after controlling demographic variables age, sex, income, education, race/ethnicity, and BMI. BMI did not serve as a moderator in the relationship between menu type and food calories ordered. Implications for policy change and clinical work with overweight and obese patients are discussed.

  1. Dietitian perceptions of low-calorie sweeteners.

    PubMed

    Harricharan, Michelle; Wills, Josephine; Metzger, Nathalie; de Looy, Anne; Barnett, Julie

    2015-06-01

    Lowering energy (calorie) intake is essential in managing a healthy weight. One method of doing this is substituting sugar with low/no-calorie sweeteners. The safety of sweeteners has been debated, but little is known about how they are perceived by professionals responsible for weight management advice. We sought to explore dietitian perceptions of sweeteners and to identify the practical advice they provide about them. We collected data in France, Germany, Hungary, Portugal and the United Kingdom. We used face-to-face interviews and a novel online tool designed to engage people with online content in a way that approximates everyday processes of making sense of information. We identified four approaches to sweeteners that dietitians took: (1) sweeteners should not be used, (2) they should be limited and used primarily as a transitional product, (3) sweetener use was decided by the client and (4) sweeteners should be recommended or at least allowed. Where dietitians are reticent to recommend sweeteners this is because they feel it is important for consumers to reduce their attachment to sweet tastes and of evidence linking the consumption of sweeteners to increased appetite. There is also uncertainty about the possible negative health effects of sweeteners. Dietitians' perceptions about sweeteners are uncertain, ambivalent and divergent, sometimes explicitly being linked to fears about adverse health effects. Clear and authoritative guidance is required on scientific evidence around sweeteners as well as the ways in which they can be used in dietetic practice. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  2. International trends in lifelong learning for pharmacists.

    PubMed

    Driesen, Annelies; Verbeke, Koen; Simoens, Steven; Laekeman, Gert

    2007-06-15

    Lifelong learning for community pharmacists is shifting from continuing education (CE) towards continuing professional development (CPD) in some countries. The objectives of this report were to compare lifelong learning frameworks for community pharmacists in different countries, and determine to what extent the concept of CPD has been implemented. A literature search was conducted as well as an Internet search on the web sites of professional pharmacy associations and authorities in 8 countries. The results of this review show that the concept of CPD has been implemented primarily in countries that have a long tradition in lifelong learning, such as Great Britain. However, most countries have opted for the CE approach, eg, France, or for a combination of CE and CPD, eg, New Zealand. This approach combines the controllability by regulatory organizations that CE requires with the advantage of sustained behavior change seen in successful CPD programs.

  3. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... In a case of restrictive cardiomyopathy, the heart muscle is of normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does ...

  4. Effect of calorie or exercise labels on menus on calories and macronutrients ordered and calories from specific foods in Hispanic participants: a randomized study.

    PubMed

    Shah, Meena; Bouza, Brooke; Adams-Huet, Beverley; Jaffery, Manall; Esposito, Phil; Dart, Lyn

    2016-12-01

    The effect of menu labels on food choices is unknown in Hispanics. This study evaluated the impact of menu labels on calories and macronutrients ordered in Hispanics. 372 Hispanics (18-65 years) were randomly assigned to menus with no labels (NL) (n=127), rank-ordered calorie labels plus a statement on energy needs per meal (CL) (n=123), or rank-ordered exercise labels showing minutes of brisk walking necessary to burn the food calories (EL) (n=122). The menus had identical food choices. Participants were instructed to select foods from the assigned menu as if having lunch in a fast food restaurant. One-way analysis of variance found no difference in calories ordered (median (25th and 75th centiles)) by menu condition (NL: 785.0 (465.0, 1010.0) kcal; CL: 790.0 (510.0, 1020.0) kcal; EL: 752.5 (520.0, 1033.8) kcal; p=0.75). Calories from specific foods and macronutrient intake were not different by menu condition. Menu label use was 26.8% in the CL and 25.4% in the EL condition. Calories ordered were not different between those who used and those who did not use the labels. Regression analysis showed that perception of being overweight (p=0.02), selecting foods based on health value (p<0.0001), and meeting exercise guidelines (p<0.0001) were associated with fewer calories ordered. Logistic regression showed that selecting foods based on health value (p=0.01) was associated with higher food label use. Menu labels did not affect food choices in Hispanic participants. Future studies should determine if nutrition, exercise, and weight perception counseling prior to menu labels intervention would result in better food choices. NCT02804503; post-results. Copyright © 2016 American Federation for Medical Research.

  5. Informal science education: lifelong, life-wide, life-deep.

    PubMed

    Sacco, Kalie; Falk, John H; Bell, James

    2014-11-01

    Informal Science Education: Lifelong, Life-Wide, Life-Deep Informal science education cultivates diverse opportunities for lifelong learning outside of formal K-16 classroom settings, from museums to online media, often with the help of practicing scientists.

  6. Educational Reform in Japan for Lifelong Learning

    ERIC Educational Resources Information Center

    Kawachi, Paul

    2008-01-01

    This report describes the current state of affairs and reform in Japan in 2007 of the theory, policy, and practice of lifelong education. As in most countries, Japan has been talking of decentralisation in government, of giving more local autonomy to communities and of promoting individuality in education. In line with these aims, the government…

  7. Lifelong Learning in Nepal: Contexts and Prospects

    ERIC Educational Resources Information Center

    Regmi, Kapil Dev

    2011-01-01

    Learning is a lifelong process. Many countries in the world, basically the European and Organization for Economic Cooperation and Development (OECD) countries, have adopted it as an important vehicle for human development. They have also made it a policy agenda for meeting the human capital need for twenty first century for economic prosperity.…

  8. Lifelong Learning: Workforce Development and Economic Success.

    ERIC Educational Resources Information Center

    Lee, Alice

    Lifelong learning through a strong, policy-supported information technology (IT) infrastructure is critical to the success of Asia Pacific Economic Cooperation (APEC) member economies. There is a great need to upgrade the quality of skills within the workforce, and there have been unprecedented investments in infrastructure and advanced…

  9. Lifelong Learning and the Limits of Tolerance

    ERIC Educational Resources Information Center

    Bagnall, Richard G.

    2006-01-01

    Lifelong education or learning theory is presented by its apologists as a universal normative ethic. That ethic may be understood as an aretaic ethic, embracing a number of ethical values or informed commitments and a teleology of optimising universal human flourishing through learning. In an effort to examine possible barriers to the universality…

  10. Elders' Lifelong Connection with the Natural Environment

    ERIC Educational Resources Information Center

    Carman, Jack

    2011-01-01

    Our interaction with nature does not end just because we age. People have a lifelong connection with the outdoor environment in varying degrees. For some, this participation may be subtle by simply watching others interact with the outdoor environment. For others, there is a deeper connection with nature through gardening, birding, exercise,…

  11. Lifelong Learning within HE in The Netherlands

    ERIC Educational Resources Information Center

    van den Dungen, Marja

    2009-01-01

    This article focuses on work-based learning in higher vocational education and training in relation to lifelong learning. It begins with an overview of the Dutch National Policy and the ambitions of a national Project Directorate Learning & Working. It then goes on to the concrete results of projects within higher education (HE) aimed at the…

  12. Flexible Querying of Lifelong Learner Metadata

    ERIC Educational Resources Information Center

    Poulovassilis, A.; Selmer, P.; Wood, P. T.

    2012-01-01

    This paper discusses the provision of flexible querying facilities over heterogeneous data arising from lifelong learners' educational and work experiences. A key aim of such querying facilities is to allow learners to identify possible choices for their future learning and professional development by seeing what others have done. We motivate and…

  13. The Philosophical Roots of Lifelong Learning.

    ERIC Educational Resources Information Center

    Lewis, Rosa B.

    The philosophical roots of the concept of lifelong learning are considered in relation to the views of Socrates, Plato, and Aristotle. They pioneered in their analyses of intellectual development and in the importance of the use of the mind throughout the life span. Plato and Aristotle added metaphysical arguments to support their systems of…

  14. Designing Instruction to Improve Lifelong Inquiry Learning

    ERIC Educational Resources Information Center

    Lin, Marcia C.; Eylon, Bat-Sheva; Rafferty, Anna; Vitale, Jonathan M.

    2015-01-01

    Citizens need the capability to conduct their own inquiry projects so that they can make sense of claims about new energy policies, health remedies, or financial opportunities. To develop the lifelong capability to grapple with these dilemmas, we report on ways to design precollege units that engage students in realistic, personally relevant…

  15. The Waikiki Lifelong Learning Center. Final Report.

    ERIC Educational Resources Information Center

    Ching, Noelani; Mahuka, Ruth

    The Waikiki Lifelong Learning Center (WLLC) project was undertaken to establish a literacy consortium of visitor industry businesses and the University of Hawaii at Manoa and to develop/implement an instructional program that included bilingual/English-as-a-second language (ESL) and General Educational Development (GED)/pre-GED components. After…

  16. Students' Plans for Lifelong Learning and Teaching

    ERIC Educational Resources Information Center

    Plavšic, Marlena; Dikovic, Marina

    2015-01-01

    One of the roles of higher education is to prepare and encourage students for lifelong learning. However, no evidence can be found about students' plans for further learning and teaching related to formal, non-formal and informal context. The purpose of this study was to explore these students' plans in relation to their study group, level of…

  17. Promoting Lifelong Learning through Education Partnership.

    ERIC Educational Resources Information Center

    Berkeley, John

    1998-01-01

    The Rover Group, a British auto manufacturer, supports work-related curriculum through partnership centers at its major plants and school-based facilities, annual awards, and learning agreements for students in work experience programs. Quality, long-term commitment, and promotion of lifelong learning remain relevant but elusive goals. (SK)

  18. Lifelong Learning for the Global Networked Society.

    ERIC Educational Resources Information Center

    Guest, Graham

    Professionals have normally become qualified through a period of formal education followed by a structured training program and continuing professional development. This traditional pattern is being replaced with a process of lifelong learning that, thanks to the development and application of a wide range of information and communication…

  19. Changing Lives through Lifelong Learning Accounts

    ERIC Educational Resources Information Center

    Council for Adult and Experiential Learning (NJ1), 2007

    2007-01-01

    As conceived by the Council for Adult and Experiential Learning (CAEL), Lifelong Learning Accounts (LiLAs[SM]) are employer-matched, portable individual accounts used to finance employee education and training. They provide employees with an affordable means of upgrading their skills and knowledge, while helping to meet the needs of employers and…

  20. Credit for Lifelong Learning. Fourth Edition.

    ERIC Educational Resources Information Center

    Mann, Carolyn M.

    This guide to developing a prior learning portfolio was prepared to assist students in the Credit for Lifelong Learning Program (CLLP) at Sinclair Community College (SCC) in Dayton, Ohio, through the process of identifying college-level prior learning, matching their learning to specific courses, and articulating and documenting their learning.…