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Objective: The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus daily calorie restriction (CR) on sleep quality, duration, insomnia severity, and risk of obstructive sleep apnea in adults with obesity over one year. Methods: A total of 90 participants were randomized to one of three groups for 12 months: 8 h TRE (eating only between 12 p.m. and 8 p.m.); CR (25% daily calorie restriction) or a no-intervention control group. Results: By the end of the study, weight loss was 4.61 kg (95% CI; 7.37 to 1.85 kg; p ≤ 0.01) for the TRE group and 5.42 kg (CI; 9.13 to 1.71 kg; p ≤ 0.01) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI; 3.07 to 4.69]; p = 0.68]). Self-reported sleep quality, sleep duration, insomnia severity, and risk of obstructive sleep apnea did not change in the TRE or CR groups versus controls by month 12. Conclusions: These findings suggest that the weight loss produced by TRE and CR does not have any impact on various sleep parameters in adults with obesity over one year. [ABSTRACT FROM AUTHOR]

Objectives: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. Methods: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Results: Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e., with ketones) and dietary strategies that impact ketogenesis. Conclusion: This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies in preventing progression and improving outcomes in the context of HF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is currently a growing interest in diets and physical activity patterns that may be beneficial in preventing and treating breast cancer (BC). Mounting evidence indicates that indeed, the so-called Mediterranean diet (MedDiet) and regular physical activity likely both help reduce the risk of developing BC. For those who have already received a BC diagnosis, these interventions may decrease the risk of tumor recurrence after treatment and improve quality of life. Studies also show the potential of other dietary interventions, including fasting or modified fasting, calorie restriction, ketogenic diets, and vegan or plant-based diets, to enhance the efficacy of BC therapies. In this review article, we discuss the biological rationale for utilizing these dietary interventions and physical activity in BC prevention and treatment. We highlight published and ongoing clinical studies that have applied these lifestyle interventions to BC patients. This review offers valuable insights into the potential application of these dietary interventions and physical activity as complimentary therapies in BC management. [ABSTRACT FROM AUTHOR]

In diabetes, pancreatic β-cells gradually lose their ability to secrete insulin with disease progression. β-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by β-cell dedifferentiation and identified in diabetic animals, has attracted attention as an underlying molecular mechanism of β-cell dysfunction. Previously, we reported β-cell dedifferentiation suppression by calorie restriction, not by reducing hyperglycemia using hypoglycemic agents (including sodium-glucose cotransporter inhibitors), in an obese diabetic mice model (db/db). Here, to explore further mechanisms of the effects of food intake on β-cell function, db/db mice were fed either a high-carbohydrate/low-fat diet (db-HC) or a low-carbohydrate/high-fat diet (db-HF) using similar calorie restriction regimens. After one month of intervention, body weight reduced, and glucose intolerance improved to a similar extent in the db-HC and db-HF groups. However, β-cell dedifferentiation did not improve in the db-HC group, and β-cell mass compensatory increase occurred in this group. More prominent fat accumulation occurred in the db-HC group livers. The expression levels of genes related to lipid metabolism, mainly regulated by peroxisome proliferator-activated receptor α and γ, differed significantly between groups. In conclusion, the fat/carbohydrate ratio in food during calorie restriction in obese mice affected both liver lipid metabolism and β-cell dedifferentiation. [ABSTRACT FROM AUTHOR]

Epilepsy often occurs with other neurological disorders, such as autism, affective disorders, and cognitive impairment. Research indicates that many neurological disorders share a common pathophysiology of dysfunctional energy metabolism, neuroinflammation, oxidative stress, and gut dysbiosis. The past decade has witnessed a growing interest in the use of metabolic therapies for these disorders with or without the context of epilepsy. Over one hundred years ago, the high-fat, low-carbohydrate ketogenic diet (KD) was formulated as a treatment for epilepsy. For those who cannot tolerate the KD, other diets have been developed to provide similar seizure control, presumably through similar mechanisms. These include, but are not limited to, the medium-chain triglyceride diet, low glycemic index diet, and calorie restriction. In addition, dietary supplementation with ketone bodies, polyunsaturated fatty acids, or triheptanoin may also be beneficial. The proposed mechanisms through which these diets and supplements work to reduce neuronal hyperexcitability involve normalization of aberrant energy metabolism, dampening of inflammation, promotion of endogenous antioxidants, and reduction of gut dysbiosis. This raises the possibility that these dietary and metabolic therapies may not only exert anti-seizure effects, but also reduce comorbid disorders in people with epilepsy. Here, we explore this possibility and review the clinical and preclinical evidence where available. [ABSTRACT FROM AUTHOR]

This study assesses the feasibility of calorie restriction (CR) and time-restricted feeding (TRF) in overweight and obese cancer patients who realized little to no physical activity undergoing curative radiotherapy, structured as a prospective, interventional, non-randomized open-label clinical trial. Of the 27 participants initially enrolled, 21 patients with breast cancer were selected for analysis. The participants self-selected into two dietary interventions: TRF, comprising a sugar and saturated fat-free diet calibrated to individual energy needs consumed within an 8 h eating window followed by a 16 h fast, or CR, involving a 25% reduction in total caloric intake from energy expenditure distributed across 4 meals and 1 snack with 55% carbohydrates, 15% protein, and 30% fats, excluding sugars and saturated fats. The primary goal was to evaluate the feasibility of these diets in the specific patient group. The results indicate that both interventions are effective and statistically significant for weight loss and reducing one's waist circumference, with TRF showing a potentially stronger impact and better adherence. Changes in the LDL, HDL, total cholesterol, triglycerides, glucose and insulin were not statistically significant. [ABSTRACT FROM AUTHOR]

It has emerged the gut microbiome is crucially linked to metabolic health and obesity. Macronutrient distribution has been discussed as a key parameter in weight-loss programs, but little is known about its impact on the gut microbiome. We investigated the effects of weight-loss meal replacement programs with different macronutrient ratios on the gut microbiota and metabolic parameters in subjects with overweight and obesity. Three low-calorie meal replacement programs with different ratios of carbohydrates, proteins, and lipids were designed: a balanced diet (Group B, 60:15:30), a high-lipid−low-carbohydrate diet (Group F, 35:20:55), and a protein-enriched diet (Group P, 40:25:35). Sixty overweight or obese participants were provided with the meals twice daily for 3 weeks. In all groups, diet intervention resulted in reduced body weight and BMI. The relative abundance of Bacteroidetes and Firmicutes phyla decreased and increased, respectively, which increased the Firmicutes/Bacteroidetes (F/B) ratio in all subjects, particularly in Groups B and P. Alpha- and beta-diversity were augmented at the phylum level in Group P. In conclusion, short-term interventions with weight-loss meal replacement programs increased butyrate-producing bacteria and the F/B ratio. Moreover, the protein-enriched diet significantly increased alpha- and beta-diversity compared to the balanced diet and the high-lipid−low-carbohydrate diet. [ABSTRACT FROM AUTHOR]

The purpose of this secondary analysis is to compare the effects of two popular weight loss regimens, time-restricted eating (TRE) and daily calorie restriction (CR), on mood and quality-of-life measures in adults with obesity. Ninety participants were randomized to one of three interventions for 12 months: 8 h TRE (eating only between 12:00 and 8:00 p.m., with no calorie counting); CR (25% energy restriction daily); or no-intervention control group. Questionnaires were administered to measure mood (Beck Depression Inventory-II (BDI-II), and Profile of Mood States (POMS)) and quality of life (Rand 36-Item Short Form) at baseline and month 12. Body weight decreased in the TRE group (−4.87%, 95%CI: −7.61, −2.13) and CR group (−5.30%, 95%CI: −9.06, −1.54) versus controls, with no difference between TRE and CR. The BDI-II depression score did not change in the TRE or CR group, versus controls, by month 12. Likewise, there were no changes in any of the POMS subscales (tension, depression, anger, fatigue, anger, confusion, or vigor) or the total mood disturbance score in the TRE or CR group versus controls. As for quality of life, there were no significant changes in the SF-36 constructs of mental health, bodily pain, and general physical health in the TRE or CR group versus controls. However, there was a trend towards increased vitality in the TRE group (7.77 [95% CI: 0.15, 15.39] p = 0.05) relative to controls. There were no associations between changes in body weight, physical activity, mood, and quality of life in any group by the end of the study. These findings suggest that TRE and CR produce similar degrees of weight loss, but impact neither mood nor quality of life in adults with obesity over 12 months. Future well-powered studies will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer in women worldwide. The risk of developing postmenopausal breast cancer is exacerbated by obesity (BMI > 30 kg/m2), and growing evidence suggests that obesity increases the risk of developing triple-negative breast cancer. Calorie restriction (CR), a reduction of calorie intake by 20–40% without causing malnutrition, is associated with decreasing an individual's risk of developing cancer, enhancing the responses to cancer treatment, and reducing the risk of breast cancer recurrence. The negative impact of CR on breast cancer growth may result from lowering bioavailable levels of IGF1. In this study, we suggest that CR's antitumor effects are partly mediated by the upregulation of miR-15b, which downregulates IGF1R and other target genes involved in cell cycle control. Our findings suggest that miR-15b could mediate CR's regulation of IGF1/IGF1R signaling that contributes to the anticancer properties of this dietary intervention. Calorie restriction (CR) inhibits triple-negative breast cancer (TNBC) progression in several preclinical models in association with decreased insulin-like growth factor 1 (IGF1) signaling. To investigate the impact of CR on microRNAs (miRs) that target the IGF1/IGF1R pathway, we used the spontaneous murine model of TNBC, C3(1)/SV40 T-antigen (C3-TAg). In C3-TAg mice, CR reduced body weight, IGF1 levels, and TNBC progression. We evaluated the tumoral expression of 10 miRs. CR increased the expression of miR-199a-3p, miR-199a-5p, miR-486, and miR-15b. However, only miR-15b expression correlated with tumorigenicity in the M28, M6, and M6C C3-TAg cell lines of TNBC progression. Overexpressing miR-15b reduced the proliferation of mouse (M6) and human (MDA-MB-231) cell lines. Serum restriction alone or in combination with low levels of recombinant IGF1 significantly upregulated miR-15b expression and reduced Igf1r in M6 cells. These effects were reversed by the pharmacological inhibition of IGFR with BMS754807. In silico analysis using miR web tools predicted that miR-15b targets genes associated with IGF1/mTOR pathways and the cell cycle. Our findings suggest that CR in association with reduced IGF1 levels could upregulate miR-15b to downregulate Igf1r and contribute to the anticancer effects of CR. Thus, miR-15b may be a therapeutic target for mimicking the beneficial effects of CR against TNBC. [ABSTRACT FROM AUTHOR]

(1) Background: Although the important role of dietary energy intake in regulating both cancer progression and host immunity has been widely recognized, it remains unclear whether dietary calorie restriction (CR) has any impact on anti-tumor immune responses. (2) Methods: Using an immunogenic B16 melanoma cell expressing ovalbumin (B16-OVA), we examined the effect of the CR diet on B16-OVA tumor growth and host immune responses. To further test whether the CR diet affects the efficacy of cancer immunotherapy, we examined the effect of CR against anti-PD-1 monoclonal antibody (anti-PD-1 Ab) treatment. (3) Results: The CR diet significantly slowed down the tumor growth of B16-OVA without affecting both CD4+ and CD8+ T cell infiltration into the tumor. Although in vivo depletion of CD8+ T cells facilitated B16-OVA tumor growth in the control diet group, there was no significant change in the tumor growth in the CR diet group with or without CD8+ T cell-depletion. Anti-PD-1 Ab treatment lost its efficacy to suppress tumor growth along with the activation and metabolic shift of CD8+ T cells under CR condition. (4) Conclusions: Our present results suggest that a physical condition restricted in energy intake in cancer patients may impair CD8+ T cell immune surveillance and the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = −0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group. [ABSTRACT FROM AUTHOR]

Background and aims: Sepsis-related liver failure is associated with a particularly unfavorable clinical outcome. Calorie restriction is a well-established factor that can increase tissue resilience, protect against liver failure and improve outcome in preclinical models of bacterial sepsis. However, the underlying molecular basis is difficult to investigate in animal studies and remains largely unknown. Methods: We have used an immortalized hepatocyte line as a model of the liver parenchyma to uncover the role of caloric restriction in the resilience of hepatocytes to inflammatory cell damage. In addition, we applied genetic and pharmacological approaches to investigate the contribution of the three major intracellular nutrient/energy sensor systems, AMPK, mTORC1 and mTORC2, in this context. Results: We demonstrate that starvation reliably protects hepatocytes from cellular damage caused by pro-inflammatory cytokines. While the major nutrient- and energy-related signaling pathways AMPK, mTORC2/Akt and mTORC1 responded to caloric restriction as expected, mTORC1 was paradoxically activated by inflammatory stress in starved, energy-deprived hepatocytes. Pharmacological inhibition of mTORC1 or genetic silencing of the mTORC1 scaffold Raptor, but not its mTORC2 counterpart Rictor, abrogated the protective effect of starvation and exacerbated inflammation-induced cell death. Remarkably, mTORC1 activation in starved hepatocytes was uncoupled from the regulation of autophagy, but crucial for sustained protein synthesis in starved resistant cells. Conclusions: AMPK engagement and paradoxical mTORC1 activation and signaling mediate protection against pro-inflammatory stress exerted by caloric restriction in hepatocytes. [ABSTRACT FROM AUTHOR]

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Many investigations have been devoted to the effects of calorie restriction on cancer development in vitro and in vivo. It was revealed that fasting can regulate the activity of the signal cascades including AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), p53, mTOR, insulin/ insulin-like growth factor 1 (IGF1) and JAK-STAT. Up- or down-regulation of the pathways results in the decrease of cancer cell proliferation, migration and survival and the increase of apoptosis and effects of chemotherapy. The aim of this review is to discuss the connection between obesity and cancer development and the mechanisms of calorie restriction influence on cancerogenesis that stress the importance of further research of calorie restriction effects for the inclusion of this approach in clinical practice. [ABSTRACT FROM AUTHOR]

Initially, protein aggregates were regarded as a sign of a pathological state of the cell. Later, it was found that these assemblies are formed in response to stress, and that some of them serve as signalling mechanisms. This review has a particular focus on how intracellular protein aggregates are related to altered metabolism caused by different glucose concentrations in the extracellular environment. We summarise the current knowledge of the role of energy homeostasis signalling pathways in the consequent effect on intracellular protein aggregate accumulation and removal. This covers regulation at different levels, including elevated protein degradation and proteasome activity mediated by the Hxk2 protein, the enhanced ubiquitination of aberrant proteins through Torc1/Sch9 and Msn2/Whi2, and the activation of autophagy mediated through ATG genes. Finally, certain proteins form reversible biomolecular aggregates in response to stress and reduced glucose levels, which are used as a signalling mechanism in the cell, controlling major primary energy pathways related to glucose sensing. [ABSTRACT FROM AUTHOR]

Simple Summary: Our daily life follows 24-h cycles in various biological functions, such as sleep–wake and feeding/fasting cycles. These rhythms are regulated by endogenous clocks that are synchronized by environmental cues. In mammals, the main circadian clock is located in the suprachiasmatic nuclei at the basis of the brain and can be reset by ambient light, be it natural or artificial. Many secondary clocks, located in the various brain areas and peripheral organs, are regulated by the main circadian clock via the autonomic nervous system, hormonal secretions, and also by meal times. Numerous studies have underlined the importance of circadian rhythmicity for good metabolic health. Moreover, circadian disruption has a negative impact on metabolism, with increased metabolic risks, such as obesity and diabetes. Based on research with animal models and clinical and epidemiological studies in humans, some mechanistic insights are given to explain why circadian disruption, such as exposure to bright light at night or nocturnal meals, can have detrimental effects on energy balance in humans, and how timed nutrition and sleep may counteract or limit these adverse health effects. Like other biological functions, food intake and energy metabolism display daily rhythms controlled by the circadian timing system that comprises a main circadian clock and numerous secondary clocks in the brain and peripheral tissues. Each secondary circadian clock delivers local temporal cues based on intracellular transcriptional and translational feedback loops that are tightly interconnected to intracellular nutrient-sensing pathways. Genetic impairment of molecular clocks and alteration in the rhythmic synchronizing cues, such as ambient light at night or mistimed meals, lead to circadian disruption that, in turn, negatively impacts metabolic health. Not all circadian clocks are sensitive to the same synchronizing signals. The master clock in the suprachiasmatic nuclei of the hypothalamus is mostly synchronized by ambient light and, to a lesser extent, by behavioral cues coupled to arousal and exercise. Secondary clocks are generally phase-shifted by timed metabolic cues associated with feeding, exercise, and changes in temperature. Furthermore, both the master and secondary clocks are modulated by calorie restriction and high-fat feeding. Taking into account the regularity of daily meals, the duration of eating periods, chronotype, and sex, chrononutritional strategies may be useful for improving the robustness of daily rhythmicity and maintaining or even restoring the appropriate energy balance. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) and exercise training (EX) are two critical lifestyle interventions for the prevention and treatment of metabolic diseases, such as obesity and diabetes. Brown adipose tissue (BAT) and skeletal muscle are two important organs for the generation of heat. Here, we undertook detailed transcriptional profiling of these two thermogenic tissues from mice treated subjected to CR and/or EX. We found transcriptional reprogramming of BAT and skeletal muscle as a result of CR but little from EX. Consistent with this, CR induced alterations in the expression of genes encoding adipokines and myokines in BAT and skeletal muscle, respectively. Deconvolution analysis showed differences in the subpopulations of myogenic cells, mesothelial cells and endogenic cells in BAT and in the subpopulations of satellite cells, immune cells and endothelial cells in skeletal muscle as a result of CR or EX. NicheNet analysis, exploring potential inter-organ communication, indicated that BAT and skeletal muscle could mutually regulate their fatty acid metabolism and thermogenesis through ligands and receptors. These data comprise an extensive resource for the study of thermogenic tissue molecular responses to CR and/or EX in a healthy state. [ABSTRACT FROM AUTHOR]

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment. [ABSTRACT FROM AUTHOR]

Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR. [ABSTRACT FROM AUTHOR]

Introduction: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function. Methods: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity). Results: Participants' mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5–125.7; p = 0.045) and reduced BMI by 0.8 kg/m2 (95%CI: −1.349–−0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: −69.910–−10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, β = −0.071; CI95%:−0.136–−0.006; p = 0.033; β = 7.486; CI95%:0.350–14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (β = 0.818; CI95%:0.044–1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (β = 0.002; CI95%:0.000–0.003; p = 0.022) and total conjugated diene generation (β = 0.001; CI95%:0.000–0.001; p = 0.029). Conclusion: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is a major regulator of skeletal myocyte viability. The signaling pathways triggered by mTOR vary according to the type of endogenous and exogenous factors (e.g., redox balance, nutrient availability, physical activity) as well as organismal age. Here, we provide an overview of mTOR signaling in skeletal muscle, with a special focus on the role played by mTOR in the development of sarcopenia. Intervention strategies targeting mTOR in sarcopenia (e.g., supplementation of plant extracts, hormones, inorganic ions, calorie restriction, and exercise) have also been discussed. [ABSTRACT FROM AUTHOR]

To retrospectively review the efficacy of intermittent fasting 5:2 plus program (30% of energy requirements on fast days and 70% of energy requirements on nonfasting days) in Chinese patients with overweight or obesity. This retrospective cohort study evaluated weight loss outcomes of patients treated with 12 weeks weight loss program in clinic. Adults with overweight or obesity participated in intermittent fasting 5:2 plus, daily calorie restriction (70% of energy requirements every day) or daily calorie restriction with meal replacement (70% of energy requirements every day, partly provided with high-protein meal replacement) programs for 12 weeks. The primary objective was to compare the weight loss of three groups. The primary outcome measure was the change in the % total weight loss. A total of 131 patients (35.3 ± 10.1 years; 81.7% female) were included, and the mean weight loss was 7.8 ± 4.4% after 12 weeks. The intermittent fasting 5:2 plus group (n = 42) achieved 9.0 ± 5.3% weight loss, compared with 5.7 ± 3.7% in the daily calorie restriction group (n = 41) (p < 0.001) and 8.6 ± 3.5% in the meal replacement group (n = 48) (p = 0.650). A total of 85.7% of patients in the intermittent fasting 5:2 plus group lost more than 5% body weight, vs. 58.5% in the daily calorie restriction group (p = 0.008), and 45.2% lost more than 10% body weight, vs. 14.6% in the daily calorie restriction group (p = 0.005). No serious adverse events were reported in the three groups. The intermittent fasting 5:2 plus program more effectively led to weight loss than daily calorie restriction in the short-term in Chinese patients with overweight or obesity. A longer-term prospective randomized controlled trial is needed. [ABSTRACT FROM AUTHOR]

Further examination of the molecular regulators of long-term calorie restriction (CR), reported to have an anxiolytic effect, may highlight novel therapeutic targets for anxiety disorders. Here, adult male Hooded Wistar rats were exposed to a 25% CR whilst anxiety-like behaviour was assessed at 6-, 12-, and 18-months of age via the elevated plus maze, open field, and acoustic startle tests. Next-generation sequencing was then used to measure transcriptome-wide gene expression in the hypothalamus, amygdala, pituitary, and adrenal glands. Results showed an anxiolytic behavioural profile across early, middle, and late adulthood by CR, with the strongest effects noted at 6-months. Transcriptomic analysis by seven attribute weighting algorithms, including Info Gain Ratio, Rule, Chi Squared, Gini Index, Uncertainty, Relief, and Info Gain, led to the development of a signature of long-term CR, independent of region. Complement C1q A chain (C1qa), an extracellular protein, expression was significantly decreased by CR in most regions examined. Furthermore, text mining highlighted the positive involvement of C1qa in anxiety, depression, neurodegeneration, stress, and ageing, collectively identifying a suitable biomarker candidate for CR. Overall, the current study identified anxiety-related phenotypic changes and a novel transcriptome signature of long-term CR, indicating potential therapeutic targets for anxiety, depression, and neurodegeneration. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has been shown to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers/pathways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes/pathways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on healthspan and lifespan. [ABSTRACT FROM AUTHOR]

Calorie restriction enhances stem cell self-renewal in various tissues, including the mammary gland. We hypothesized that similar to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in energy supply, depending instead on niche signaling. The latter was investigated by subjecting cultures of mammary epithelial stem cells for 8 days to in vivo paracrine calorie-restriction signals collected from a 4-day-conditioned medium of individual mammary cell populations. Conditioned medium from calorie-restricted non-epithelial cells induced latent cell propagation and mammosphere formation—established markers of stem cell self-renewal. Combined RNA-Seq, immunohistochemistry and immunofluorescence analyses of the non-epithelial population identified macrophages and secreted CSF1 as the energy sensor and paracrine signal, respectively. Calorie restriction-induced pStat6 expression in macrophages suggested that skewing to the M2 phenotype contributes to the sensing mechanism. Enhancing CSF1 signaling with recombinant protein and interrupting the interaction with its highly expressed receptor in the epithelial stem cells by neutralizing antibodies were both affected stem cell self-renewal. In conclusion, combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the calorie restriction-induced effect on mammary stem cell self-renewal. [ABSTRACT FROM AUTHOR]

Anxiety is a common disorder among college students, especially those with obesity. Obesity contributes to metabolic disorders and disturbs the neural functions, further leading to anxiety. In this cross-sectional study, we aimed to determine the association between obesity and anxiety among college students and identified the potential factors for obesity-associated anxiety. We evaluated the intervention effects of calorie restriction on anxiety. Self-reported questionnaires were distributed to 1381 college students from January to March in 2021. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were classified into anxiety and non-anxiety groups according to their STAI scores. Chi-squared test and logistic regression were used to analyze the potential factors. We found that 383 college students exhibited anxiety, accounting for 30.1% among all included college students, which was higher than the global average. The association between anxiety and obesity was observed among college students (p = 0.009), especially in males (p = 0.007). We identified that pre-obesity (p = 0.012), unhealthy calorie intake (p = 0.001), dieting (p = 0.003) and high academic year (p = 0.006) as the risk factors for anxiety and found that the long sleep duration was a protective factor for anxiety (p < 0.001). We found that more obese students showed an improvement of anxiety than the underweight students after calorie restriction (p < 0.001). Collectively, our findings suggest that obesity-associated anxiety is prevalent among the college students and could be alleviated by moderate calorie restriction. It is necessary for students to receive anxiety management in their college life. Additionally, the proper calorie restriction should be promoted to help students protect against obesity and obesity-associated anxiety. [ABSTRACT FROM AUTHOR]

The Ramadan fasting period (RFP) means abstaining from consuming food and/or beverages during certain hours of the day—from sunrise to sunset. Engaging in exercise and sports during the RFP leads to the lipolysis of adipose tissue and an increase in the breakdown of peripheral fat, leading to an increase in fat consumption. The effects of the RFP on functional, hematological, and metabolic parameters needs further study as existing studies have reported contradictory results. The differences in the results of various studies are due to the geographical characteristics of Muslim athletes, their specific diets, and their genetics, which explain these variations. In recent years, the attention of medical and sports researchers on the effects of the RFP and energy restrictions on bodily functions and athletic performance has increased significantly. Therefore, this brief article examines the effects of the RFP on the immune system, body composition, hematology, and the functionality of athletes during and after the RFP. We found that most sporting activities were performed during any time of the day without being affected by Ramadan fasting. Athletes were able to participate in their physical activities during fasting periods and saw few effects on their performance. Sleep and nutritional factors should be adjusted so that athletic performance is not impaired. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a fundamental role in the development and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of a calorie-restricted (CR) diet on oxidative/anti-oxidative status in patients with NAFLD and the potential mediating role of fibroblast growth factor 21 (FGF-21) in this regard. This randomized, controlled clinical trial was carried out on sixty patients with NAFLD aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were randomly assigned to either the CR diet group (received a prescribed low-calorie diet for twelve weeks, n = 30) or the control group (n = 30). Fasting blood samples, anthropometric measurements, dietary intake, and physical activity data were collected for all participants at baseline and at the end of the trial. Significant reductions in weight, BMI, waist circumference, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the CR diet group compared to the control group (all p < 0.05). Liver steatosis grade, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and FGF-21, as well as erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities did not show significant changes in the CR group when compared to the controls at the end of the study (p > 0.05). CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/anti-oxidative status in these patients. Future studies are warranted to target the effects of long-term interventions with a greater weight loss in this patient population. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger's test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = −0.21, 95% CI (−0.40, −0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (−0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects. [ABSTRACT FROM AUTHOR]

It has widely been accepted that food restriction (FR) without malnutrition has multiple health benefits. Various calorie restriction (CR) and intermittent fasting (IF) regimens have recently been reported to exert neuroprotective effects in traumatic brain injury (TBI) through variable mechanisms. However, the evidence connecting CR or IF to neuroprotection in TBI as well as current issues remaining in this research field have yet to be reviewed in literature. The objective of our review was therefore to weigh the evidence that suggests the connection between CR/IF with recovery promotion following TBI. Medline, Google Scholar and Web of Science were searched from inception to 25 February 2022. An overwhelming number of results generated suggest that several types of CR/IF play a promising role in promoting post-TBI recovery. This recovery is believed to be achieved by alleviating mitochondrial dysfunction, promoting hippocampal neurogenesis, inhibiting glial cell responses, shaping neural cell plasticity, as well as targeting apoptosis and autophagy. Further, we represent our views on the current issues and provide thoughts on the future direction of this research field. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) has been shown to be an effective nutritional intervention for increasing longevity in some animal species. The objective of this study was to evaluate CR's effects on metabolic and reproductive parameters in 12-month-old male Wistar rats. The rats were distributed in three groups: control, CR at 15%, and CR at 35% for 6 (up to 18 months of age) and 12 months (up to 24 months of age). At the end of CR treatment, we evaluated reproductive (male sexual behavior (MSB), sperm quality) and biochemical parameters (plasma glucose, glucose-regulating hormone, and sex steroid levels), and quantified annexin V in the seminiferous epithelium. Results showed that MSB and sperm quality were improved after 6 months of CR associated with increases in plasma testosterone and decrease annexin V in the seminiferous epithelium of the testicles compared to their control group. The metabolic profile of the CR rats also improved compared to controls. However, these effects of CR on reproductive parameters were not maintained after 12 months of CR. Findings suggest that beginning CR at the age of maturity reestablishes the behavioral sexual response and reproductive function in older animals after 6 months of CR and improves endocrine functioning during aging. [ABSTRACT FROM AUTHOR]

Mitochondrial metabolism and autophagy are two of the most metabolically active cellular processes, playing a crucial role in regulating organism longevity. In fact, both mitochondrial dysfunction or autophagy decline compromise cellular homeostasis and induce inflammation. Calorie restriction (CR) is the oldest strategy known to promote healthspan, and a plethora of CR mimetics have been used to emulate its beneficial effects. Herein, we discuss how CR and CR mimetics, by modulating mitochondrial metabolism or autophagic flux, prevent inflammatory processes, protect the intestinal barrier function, and dampen both inflammaging and neuroinflammation. We outline the effects of some compounds classically known as modulators of autophagy and mitochondrial function, such as NAD+ precursors, metformin, spermidine, rapamycin, and resveratrol, on the control of the inflammatory cascade and how these anti-inflammatory properties could be involved in their ability to increase resilience to age-associated diseases. [ABSTRACT FROM AUTHOR]

Fighting diseases and controlling the signs of ageing are the major goals of biomedicine. Sirtuins, enzymes with mainly deacetylating activity, could be pivotal targets of novel preventive and therapeutic strategies to reach such aims. Scientific proofs are accumulating in experimental models, but, to a minor extent, also in humans, that the ancient practice of calorie restriction could prove an effective way to prevent several degenerative diseases and to postpone the detrimental signs of ageing. In the present review, we summarize the evidence about the central role of sirtuins in mediating the beneficial effects of calorie restriction in skeletal and cardiac muscle since these tissues are greatly damaged by diseases and advancing years. Moreover, we entertain the possibility that the identification of sirtuin activators that mimic calorie restriction could provide the benefits without the inconvenience of this dietary style. [ABSTRACT FROM AUTHOR]

Onion (Allium cepa L.) is widely consumed as food or medicinal plant due to its well-defined health benefits. The antioxidant and antihyperlipidemic effects of onion and its extracts have been reported well. However, very limited information on anti-hyperglycemic effect is available in processed onion extracts. In our previous study, we reported that Amadori rearrangement compounds (ARCs) produced by heat-processing in Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. To prove the enhancement of anti-hyperglycemic effect and ARCs content by heat-processing in onion extract, a correlation between the anti-hyperglycemic activity and the total content of ARCs of heat-processed onion extract (ONI) was investigated. ONI has a high content of ARCs and had high rat small intestinal sucrase inhibitory activity (0.34 ± 0.03 mg/mL, IC50) relevant for the potential management of postprandial hyperglycemia. The effect of ONI on the postprandial blood glucose increase was investigated in Sprague Dawley (SD) rats fed on sucrose or starch meals. The maximum blood glucose levels (Cmax) of heat-processed onion extract were significantly decreased by about 8.7% (from 188.60 ± 5.37 to 172.27 ± 3.96, p < 0.001) and 14.2% (from 204.04 ± 8.73 to 175.13 ± 14.09, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that ARCs in onion extract produced by heat-processing have anti-diabetic effect by suppressing carbohydrate absorption via inhibition of intestinal sucrase, thereby reducing the postprandial increase of blood glucose. Therefore, enhancement of ARCs in onion by heat-processing might be a good strategy for the development of the new product on the management of hyperglycemia [ABSTRACT FROM AUTHOR]

The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H2S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory. Conclusion: animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects. [ABSTRACT FROM AUTHOR]

Few randomized controlled trials (RCT) have evaluated the efficacy of web-based programs targeting maintenance of lost weight. The aims of this study were to evaluate two versions of a commercially available web-based weight loss maintenance (WLM) program and examine whether the provision of enhanced feedback was associated with better WLM. The study was an assessor-blinded RCT of change in body mass index (BMI) over 12 months WLM. Participants were 227 adults (44% male, 42.3 ± 10.1 years, BMI 30.4 ± 4.1 kg/m²) randomized to either a basic (Basic WLM) or enhanced program with additional support (Enhanced WLM). Analysis was intention-to-treat with imputation using last observation carried forward. There was no significant weight rebound from the start of weight loss maintenance to 12 months for either group (mean: basic 1.3%, enhanced 1.5%) and limited change in secondary outcomes for either program. There were no significant between-group differences in the primary outcome of change in BMI (basic -0.5 (1.9) kg/m², enhanced -0.5 (1.6) kg/m², p = 0.93). In conclusion, a web-based WLM program was effective in preventing weight regain over one year following weight loss. However, the addition of personalized e-feedback provided limited additional benefits compared to a standard program. Given the potential reach of web-based approaches, further research examining which web-based program components optimize weight outcomes long-term is required. [ABSTRACT FROM AUTHOR]

Significant reductions in insulin resistance (IR) can be achieved by either calorie restriction or by the increase of lean mass. However, calorie restriction usually results in significant loss of lean mass. A 6-week randomized controlled feeding trial was conducted to determine if a calorie-restricted, high-protein diet (~125 g protein/day consumed evenly throughout the day) using novel functional foods would be more successful for reducing IR in comparison to a conventional diet (~80 g protein/day) with a similar level of calorie restriction. Healthy adults (age 20-75 years; body mass index, 20-42 kg/m²) with raised triglyceride/high-density lipoprotein ratios were randomly assigned to the control group (CON: test foods prepared using gluten-free commercial pasta and cereal) or to the high-protein group (HPR: test foods prepared using novel high-protein pasta and cereal both rich in wheat gluten). Mean weight loss did not differ between groups (-2.7 ± 2.6 and -3.2 ± 3.0 kg for CON (n = 11) and HPR (n = 10) respectively, p = 0.801); however, the 6-week change in fat-free mass (FFM) differed significantly between groups (-0.5 ± 1.5 and +1.5 ± 3.8 kg for CON and HPR respectively, p = 0.008). IR improved in HPR vs. CON participants (homeostasis model assessment-estimated insulin resistance [HOMAIR] change: -1.7 ± 1.4 and -0.7 ± 0.7 respectively; p = 0.020). The change in HOMA-IR was related to the change in FFM among participants (r = -0.511, p = 0.021). Thus, a high-protein diet using novel functional foods combined with modest calorie restriction was 140% more effective for reducing HOMA-IR in healthy adults compared to a lower protein, standard diet with an equal level of calorie restriction. [ABSTRACT FROM AUTHOR]

With our aging society, more people hope for a long and healthy life. In recent years, researchers have focused on healthy longevity factors. In particular, calorie restriction delays aging, reduces mortality, and extends life. Ghrelin, which is secreted during fasting, is well known as an orexigenic peptide. Because ghrelin is increased by caloric restriction, ghrelin may play an important role in the mechanism of longevity mediated by calorie restriction. In this review, we will discuss the role of orexigenic peptides with a particular focus on ghrelin. We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may play an important role in the anti-aging mechanism. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) prevalence continues to climb significantly worldwide in today's ad libitum society. MetS has tremendous societal and economic ramifications, making it imperative to develop effective strategies for preventing and controlling it to alleviate this growing burden. Periodontal disease and MetS are associated with several risk factors. Studies in the past have demonstrated that obesity, cardiovascular illness, and type 2 diabetes mellitus have a negative effect on the severity of the periodontal disease. Patients with metabolic syndrome have elevated serum levels of proinflammatory mediators such as tumor necrosis factor-alpha interleukin-6 and C-reactive protein. Similar inflammatory mediators, such as interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, are increased in patients with severe periodontal disease. Remarkably, intermittent fasting is underpinned by scientific evidence, claiming to be the most effective non-pharmacological, potential therapeutic alternative for combating a wide range of metabolic, inflammatory, and lifestyle-related diseases. Nonetheless, an insufficient investigation has been performed to determine whether intermittent fasting has therapeutic benefits on periodontal inflammation and diseases. Here, we show the interrelationship between metabolic syndrome and periodontal disease and contextualize the beneficial impact of intermittent fasting in modulating the chronic metabolic and periodontal inflammatory response. We also anticipate that this review paves the way for further exploration of intermittent fasting as a unique research paradigm representing a cost-effective alternative strategy to conventional disease management in patients with periodontal diseases and metabolic syndrome which may serve as the foundation for an integrative vision relevant to primary, diagnostic, and therapeutic purposes.

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. [ABSTRACT FROM AUTHOR]

To evaluate if experiencing a short-term exposure (18-months) to factors such as menstrual irregularities, dieting, changes in exercise or body weight, and medication usage is associated with bone mineral density (BMD) in college-aged females. A retrospective survey assessing health behaviors during a recent 18-month time period and a DXA scan were completed in 641 females. A total of 45.5% of participants reported amenorrhea during the 18-month time period. Those who experienced amenorrhea had lower femoral neck BMD ( p = 0.018), trochanter ( p = 0.018) and spine BMD ( p = 0.022) compared to eumenorrheic women. Lifetime oral contraceptive usage longer than six months was negatively associated with BMD at femoral neck ( p = 0.018) and total hip ( p = 0.021). Women who lost weight trended towards having the lowest BMD at all sites compared to women who gained weight. Following a very-low calorie diet during the time period was negatively correlated with spine BMD ( p = 0.001). Time spent in vigorous and very vigorous activity was weakly correlated with some hip BMD sites but time spent in extremely vigorous activity was not. In conclusion, females who experienced weight loss, amenorrhea, or a very low-calorie diet within an 18-month period of time in young adulthood had lower BMD. Additionally, oral contraceptive usage for longer than six months during their lifetime was associated with lower BMD.

Long non-coding RNAs (lncRNAs) play important biological roles. Here, the roles of the lncRNA KCNQ1OT1 in cellular senescence and calorie restriction were determined. KCNQ1OT1 knockdown mediated various senescence markers (increased senescence-associated β-galactosidase staining, the p53-p21Cip1/WAF1 pathway, H3K9 trimethylation, and expression of the senescence-associated secretory phenotype) and reactive oxygen species generation via CK2α downregulation in human cancer HCT116 and MCF-7 cells. Additionally, KCNQ1OT1 was downregulated during replicative senescence, and its silencing induced senescence in human lung fibroblast IMR-90 cells. Additionally, an miR-760 mimic suppressed KCNQ1OT1-mediated CK2α upregulation, indicating that KCNQ1OT1 upregulated CK2α by sponging miR-760. Finally, the KCNQ1OT1–miR-760 axis was involved in both lipopolysaccharide-mediated CK2α reduction and calorie restriction (CR)-mediated CK2α induction in these cells. Therefore, for the first time, this study demonstrates that the KCNQ1OT1–miR-760–CK2α pathway plays essential roles in senescence and CR, thereby suggesting that KCNQ1OT1 is a novel therapeutic target for an alternative treatment that mimics the effects of anti-aging and CR. [ABSTRACT FROM AUTHOR]

Abstract: Although the progressive metabolic changes associated with obesity are complex, it is well-recognized that obesity is a risk factor for the development of insulin resistance and type 2 diabetes. Because both obesity and type 2 diabetes are associated with insulin resistance, there is significant interest in defining the mechanistic basis for insulin resistance. Recent studies involving SIRT1, the most intensely studied sirtuin family member, have shown that it regulates many metabolic adaptations linked with obesity. SIRT1 has been shown to regulate the expression of adipokines, repress the activity of factors required for maturation of fat cells, regulate insulin secretion, modulate plasma glucose levels and insulin sensitivity and alter mitochondrial capacity. Moreover, some investigators have suggested that altering SIRT1 activity may be a promising new therapy for type 2 diabetes. In this review we focus on the role of sirtuins in obesity with particular emphasis on the contribution of SIRT1. [Copyright &y& Elsevier]