Extreme Calorie Restriction Research Articles

Calorie Restriction Decreases Competitive Fitness in Saccharomyces cerevisiae Following Heat Stress.

Experiments exposing Saccharomyces cerevisiae to glucose limitation (calorie restriction) are widely used to determine impacts on cell health as a model for aging. Using growth on plates and in liquid culture, we demonstrated that calorie restriction reduces fitness in subsequent nutrient-limited environments. Yeast grown in a calorie-restricted environment took longer to emerge from the lag phase, had an extended doubling time and had a lower percentage of culturability. Cells grown under moderate calorie restriction were able to withstand a gradual heat stress in a similar manner to cells grown without calorie restriction but fared less well with a sudden heat shock. Yeast grown under extreme calorie restriction were less fit when exposed to gradual heating or heat shock. Using RNAseq analysis, we provide novel insight into the mechanisms underlying this response, showing that in the absence of calorie restriction, genes whose products are involved in energy metabolism (glycolysis/gluconeogenesis and the citrate cycle) are predominantly overexpressed when yeasts were exposed to gradual heating, whereas this was not the case when they were exposed to shock. We show that both the culture history and the current environment must be considered when assaying physiological responses, and this has wider implications when developing strategies for the propagation, preservation or destruction of microbial cells.

Increased eating disorder frequency and body image disturbance among fashion models due to intense environmental pressure: a content analysis.

Female fashion models are under intense occupational pressure. The present study focuses on assessing the lived experience of fashion models with regards to their dieting and exercising habits, body image perception, eating disorder-like symptoms, and experience of abuse via self-narrated reports. Series of open questions were distributed among international fashion models (N=84, mean age=23.2 years; mean BMI=16.9) selected by convenience and snowball sampling. Models from 17 countries participated. The questions targeted models' eating, exercising, dieting habits, body image perception, and eating disorder symptoms. The average word count of the transcripts was 2473.9 (SD = 2791.6). Thematic content analysis was performed on the transcripts. A total of 31 codes were created to address disordered eating and body image concerns. Negative body-related claims appeared in 89.3%, and positive claims in 64.3% of the models' transcripts. Negative remarks about eating were made by 45.2% of the participants, and 23.8% positively. Control over their food intake was exercised by 78.6% of the participants and 40.5% used extreme calorie restriction. Models who talked more positively about their bodies expressed significantly more frequently extreme calorie restriction. Extreme sports habits occurred in 23.8% of the transcripts, obsessive sports habits were claimed by 11.9% of participants. Self-induced vomiting was prominent in 14.3% of the answers. Criticism from other industry members was experienced by 83.3% of the participants while 44.0% received body appreciation. Body image disorder-like symptoms were expressed by 63.1% of models. Such models mentioned significantly more often content about eating disorders and talked significantly more negatively about eating. Psychological problems were mentioned by 48.8%, whereas 16.7% took part in psychotherapy. Those who partake in therapy mentioned significantly more eating disorder content in their narratives. Abuse was mentioned by 25.0% of the models. Fashion models are experiencing increased environmental pressure to conform to the extreme slimness ideal. There is a heightened prevalence of disordered eating and other weight-controlling behaviours among fashion models to succeed in their careers. Qualitative research is crucial in understanding the more subtle dynamics in conforming to and maintaining the thin beauty ideal.

Severe Calorie Restriction Induces Gut Microbiota-Dependent Intestinal Stem Cell Dysfunction

Abstract Objectives Anorexia nervosa (AN) is a life-threatening illness, primarily characterized by extreme calorie restriction (CR). Given the substantial undernourishment in patients with AN, it is essential to understand the effects of severe CR on the small intestinal epithelium which is the primary tissue responsible for nutrient absorption and is therefore critical for the refeeding process. While we have previously reported that patients with AN harbor an altered intestinal microbiota, it remains unknown whether an AN-associated gut microbial community, induced by a nutrient-deprived environment, impacts intestinal epithelial physiology. Methods Conventionally-raised (CONVR) and germ-free (GF) mice were individually housed and placed on a 60% CR (60CR) diet for 9 days. CONVR mice were housed in standard specific-pathogen free conditions while GF mice were bred and housed in sterile isolators to occlude exposure to microorganisms. Mice were injected intraperitoneally with 4 mg/kg 5-ethynyl-2’deoxyuridine (EdU) 90 minutes before necropsy to mark proliferating cells. Intestinal tissue was collected for histology and intestinal crypts were isolated for ex vivo organoid culture. Results CONVR and GF mice on a 60CR diet lost significant body weight (28%±1 and 24%±1, respectively). 60CR CONVR and GF mice both displayed a significant increase in ISCs (+1.27 ± 0.02-fold and + 1.15 ± 0.05-fold, respectively) yet a significant decrease in proliferating cells (1.7 ± 0.2-fold and 1.7 ± 0.1-fold, respectively) compared to ad libitum controls. Interestingly, ex vivo organoids derived from crypts of CONVR 60CR mice were significantly smaller compared to organoids yielded from control crypts, but, strikingly, no differences in organoid size were observed between GF crypts from either diet group. Conclusions While ISC from 60CR CONVR and GF mice exhibited similar features, 60CR GF ISC function was maintained as indicated by the similar organoid growth relative to GF ad libitum controls. These data suggest that severe CR induces ISC dysfunction resulting in impaired de novo generation of digestive epithelial mass, and that these changes are microbiota-dependent. Funding Sources National Institutes of Health, North Carolina Translational and Clinical Sciences Institute, NCSU College of Veterinary Medicine, UNC Center for Gastrointestinal Biology and Disease.

During yeast chronological aging resveratrol supplementation results in a short-lived phenotype Sir2-dependent

Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD+-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging researches, it is well known that Sir2 is a positive regulator of replicative lifespan and, in this context, the RSV effects have been already examined. Here, we analyzed RSV effects during chronological aging, in which Sir2 acts as a negative regulator of chronological lifespan (CLS). Chronological aging refers to quiescent cells in stationary phase; these cells display a survival-based metabolism characterized by an increase in oxidative stress. We found that RSV supplementation at the onset of chronological aging, namely at the diauxic shift, increases oxidative stress and significantly reduces CLS. CLS reduction is dependent on Sir2 presence both in expired medium and in extreme Calorie Restriction. In addition, all data point to an enhancement of Sir2 activity, in particular Sir2-mediated deacetylation of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount of the acetylated active form of Pck1, whose enzymatic activity is essential for gluconeogenesis and CLS extension.

Seeking compulsory treatment as life-saving in the presence of eating disorders: a complex choice

Eating disorders (and especially anorexia nervosa) are associated with severe disability, poor quality of life and high mortality rate. Anorexia nervosa ranks among the main causes of death among young women. Despite physical and psycho-social impairment, patients suffering from anorexia nervosa do not recognize low body weight and extreme calorie restriction as a clinical problem and are ambivalent towards treatment. Some patients with anorexia nervosa refuse treatments though presenting severe medical complications and having a high mortality risk. Hence the need to evaluate when it could be appropriate to prescribe a compulsory treatment in the more complex cases who refuse interventions, deemed necessary for them. To date, the compulsory treatment in anorexia nervosa is still under debate: some authors take into account the negative impact on the therapeutic relationship, other authors consider it as a compassionate treatment or as life-saving therapy. Indeed, compulsory treatment for eating disorders must always be weighed very carefully because it is considered by law as the highest form of restriction of personal freedom. Political Institutions must provide a clear framework for the society and for professionals, while the health care services must face the problem of the adequacy of available resources (not only in terms of hospital beds but also of skilled professionals) compared to patients' needs, considering the organization and the integration of clinical services dedicated to the treatment of eating disorders.

Extreme calorie restriction in yeast retentostats induces uniform non-quiescent growth arrest

Non-dividing Saccharomyces cerevisiae cultures are highly relevant for fundamental and applied studies. However, cultivation conditions in which non-dividing cells retain substantial metabolic activity are lacking. Unlike stationary-phase (SP) batch cultures, the current experimental paradigm for non-dividing yeast cultures, cultivation under extreme calorie restriction (ECR) in retentostat enables non-dividing yeast cells to retain substantial metabolic activity and to prevent rapid cellular deterioration. Distribution of F-actin structures and single-cell copy numbers of specific transcripts revealed that cultivation under ECR yields highly homogeneous cultures, in contrast to SP cultures that differentiate into quiescent and non-quiescent subpopulations. Combined with previous physiological studies, these results indicate that yeast cells subjected to ECR survive in an extended G1 phase. This study demonstrates that yeast cells exposed to ECR differ from carbon-starved cells and offer a promising experimental model for studying non-dividing, metabolically active, and robust eukaryotic cells.

Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging

Nicotinamide (NAM), a form of vitamin B3, is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD+-dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast chronological aging, the established model for studying aging of postmitotic quiescent mammalian cells. Our data show that NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Δ cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. Furthermore, NAM allows the cells to push their metabolism toward the same outcomes of sir2Δ cells by elevating the level of the acetylated Pck1. Both these cells have the same metabolic changes that concern not only anabolic pathways such as an increased gluconeogenesis but also respiratory activity in terms both of respiratory rate and state of respiration. In particular, they have a higher respiratory reserve capacity and a lower non-phosphorylating respiration that in concert with a low burden of superoxide anions can affect positively chronological aging.

The Effects of a Hypocaloric Diet on Diet-Induced Thermogenesis and Blood Hormone Response in Healthy Male Adults: A Pilot Study.

Calorie restriction is a common strategy for weight loss and management. Consumption of food and nutrients stimulates diet-induced thermogenesis (DIT), as well as pancreatic and gastrointestinal hormone secretion that may regulate energy metabolism. Yet, little is known about the impact of hypocaloric diets on energy metabolism-related parameters. In this study, we assessed the effects of hypocaloric diets on hormonal variance in relation to DIT in healthy adults. Ten healthy male adults were enrolled in a randomized crossover study comprising three meal trials. Each subject was given a meal of 200 (extremely hypocaloric), 400 (moderately hypocaloric), or 800 kcal (normocaloric). Postprandial blood variables and energy expenditure were measured for 4 h (after the 200- and 400-kcal meals) or 6 h (after the 800-kcal meal). DIT and postprandial changes in blood pancreatic peptide and ghrelin were significantly smaller after the extremely or moderately hypocaloric diet than after the normocaloric diet but were similar between the hypocaloric diets. Postprandial blood insulin, amylin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide type-1 (GLP-1) increased in a calorie-dependent manner. Thermogenic efficiency (DIT per energy intake) was negatively correlated with the maximum blood level (Cmax) (p=0.01) and incremental area under the curve (p=0.01) of the blood GIP response. Calorie restriction thus leads to hormonal responses and lower DIT in healthy adults. Extreme calorie restriction, however, led to greater thermogenic efficiency compared with moderate calorie restriction. The postprandial GIP response may be a good predictor of postprandial thermogenic efficiency.

Ethanol and Acetate Acting as Carbon/Energy Sources Negatively Affect Yeast Chronological Aging

In Saccharomyces cerevisiae, the chronological lifespan (CLS) is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration.

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

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.

The Critical Role of Exercise in Weight Control

Exercise appears to play a critical role in the loss and maintenance of body weight. Diet alone has met with only temporary success because metabolic rate is decreased with extreme calorie restriction. This decrease persists after the dieting period has ended, often leading to rapid weight regain and the "yo-yo effect." In some instances, exercise alone has been effective for weight loss; however, success varies according to the gender of the subjects and to the type, intensity and duration of the exercise. Exercise programs of low to moderate intensity, long duration and high frequency seem to be most beneficial, with the most popular forms of exercise being walking/jogging, cycling and swimming. The purpose of this article is to explore the differences between diet and exercise, low vs. high intensity, short vs. long duration, and land vs. water exercise as these differences pertain to weight loss, food intake and energy balance.