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Research into the effects of calorie restriction continues to intrigue those interested in whether it may allow humans to live longer and healthier lives. Animal studies of continuous calorie restriction (CCR) and fasting have demonstrated substantial advantages to health and longevity. However, concerns remain about the impact of restricting calorie intake on human health and cognition. Given the emerging evidence of cognitive impairments in eating disorders, studies investigating restricted calorie intake in healthy humans (in an ethical way) may also have implications for understanding restrictive eating disorders. In this review, the published literature on the impact of CCR and fasting on cognitive function in healthy human participants is synthesized. Of the 33 studies of CCR and fasting in humans identified, 23 demonstrated significant changes in cognition. Despite variation across the cognitive domains, results suggest CCR benefits inhibition, processing speed, and working memory, but may lead to impairments in cognitive flexibility. The results of fasting studies suggest fasting is associated with impairments in cognitive flexibility and psychomotor abilities. Overall, the results of these studies suggest the degree (ie, the severity) of calorie restriction is what most likely predicts cognitive improvements as opposed to impairments. For individuals engaging in sustained restriction, this may have serious, irreversible consequences. However, there are mixed findings regarding the impact of CCR and fasting on this aspect of human functioning, suggesting further research is required to understand the costs and benefits of different types of calorie restriction. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) and physical exercise (EX) are well‐established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long‐term follow‐up. This study compared BioAge biomarkers in 41 middle‐aged and older adult long‐term CR practitioners, 41 age‐ and sex‐matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood‐biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi‐omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood‐derived omics, while EX participants had lower BioAge in colon mucosa‐derived epigenetic and transcriptomic markers, suggesting potential tissue‐specific effects. Multi‐omic pathway enrichment analyses suggested both shared and intervention‐specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti‐aging effects of CR and EX, offering promising directions for further research. [ABSTRACT FROM AUTHOR]

Context: Intermittent fasting, a new-age dietary concept derived from an age-old tradition, involves repetitive cycles of fasting/calorie restriction and eating. Objective: We aim to take a deep dive into the biological responses to intermittent fasting, delineate the disease-modifying and cognitive effects of intermittent fasting, and also shed light on the possible side effects. Methods: Numerous in vitro and in vivo studies were reviewed, followed by an in-depth analysis, and compilation of their implications in health and disease. Results: Intermittent fasting improves the body's stress tolerance, which is further amplified with exercise. It impacts various pathological conditions like cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. Conclusion: During dietary restriction, the human body experiences a metabolic switch due to the depletion of liver glycogen, which promotes a shift towards utilising fatty acids and ketones in the system, thereby significantly impacting adiposity, ageing and the immune response to various diseases. KEY POINTS: Intermittent fasting (IF) comprises repetitive fasting and feeding cycles. There are many variations of IF schedules. Individuals practicing an appropriate IF pattern reap numerous health benefits. The possible side effects should be considered before commencing a new IF regimen. [ABSTRACT FROM AUTHOR]

In recent years, there has been a surge in the popularity of fasting as a method to enhance one's health and overall well-being. Fasting is a customary practice characterized by voluntary refraining from consuming food and beverages for a specified duration, ranging from a few hours to several days. The potential advantages of fasting, including enhanced insulin sensitivity, decreased inflammation, and better cellular repair mechanisms, have been well documented. However, the effects of fasting on cancer therapy have been the focus of recent scholarly investigations. Doxorubicin (Dox) is one of the most widely used chemotherapy medications for cancer treatment. Unfortunately, cardiotoxicity, which may lead to heart failure and other cardiovascular issues, has been linked to Dox usage. This study aims to comprehensively examine the possible advantages and disadvantages of fasting concerning Dox-induced cardiotoxicity. Researchers have investigated the potential benefits of fasting in lowering the risk of Dox-induced cardiac damage to solve this problem. Nevertheless, new studies indicate that prolonged alternate-day fasting may adversely affect the heart's capacity to manage the cardiotoxic properties of Dox. Though fasting may benefit overall health, it is essential to proceed cautiously and consider the potential risks in certain circumstances. [ABSTRACT FROM AUTHOR]

Aging is associated with a global decline in stem cell function. To date, several strategies have been proposed to rejuvenate aged stem cells: most of these result in functional improvement of the tissue where the stem cells reside, but the impact on the lifespan of the whole organism has been less clearly established. Here, we review some of the most recent work dealing with interventions that improve the regenerative capacity of aged somatic stem cells in mammals and that might have important translational possibilities. Overall, we underscore that somatic stem cell rejuvenation represents a strategy to improve tissue homeostasis upon aging and present some recent approaches with the potential to affect health span and lifespan of the whole organism. [ABSTRACT FROM AUTHOR]

Vascular calcification is a complication that is frequently encountered in patients affected by atherosclerosis, diabetes, and chronic kidney disease (CKD), and that is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). At present, there remains a pressing lack of any effective therapies that can treat this condition. The sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) has shown beneficial effects in cardiovascular disease. The role of this inhibitor in the context of vascular calcification, however, remains largely uncharacterized. Our findings revealed that DAPA treatment was sufficient to alleviate in vitro and in vivo osteogenic transdifferentiation and vascular calcification. Interestingly, our study demonstrated that DAPA exerts its anti-calcification effects on VSMCs by directly targeting SGLT2, with the overexpression of SGLT2 being sufficient to attenuate these beneficial effects. DAPA was also able to limit the glucose levels and NAD+/NADH ratio in calcified VSMCs, upregulating sirtuin 1 (SIRT1) in a caloric restriction (CR)-dependent manner. The SIRT1-specific siRNA and the SIRT1 inhibitor EX527 attenuated the anti-calcification effects of DAPA treatment. DAPA was also to drive SIRT1-mediated deacetylation and consequent degradation of hypoxia-inducible factor-1α (HIF-1α). The use of cobalt chloride and proteasome inhibitor MG132 to preserve HIF-1α stability mitigated the anti-calcification activity of DAPA. These analyses revealed that the DAPA/SGLT2/SIRT1 axis may therefore represent a viable novel approach to treating vascular calcification, offering new insights into how SGLT2 inhibitors may help prevent and treat vascular calcification. [ABSTRACT FROM AUTHOR]

Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases. The review critically assesses the role of transcription factor EB in retinal biology during aging, its neuroprotective effects, and its therapeutic potential for retinal disorders. The impact of transcription factor EB on retinal aging is cell-specific, influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways. In vascular endothelial cells, transcription factor EB controls important processes, including endothelial cell proliferation, endothelial tube formation, and nitric oxide levels, thereby influencing the inner blood-retinal barrier, angiogenesis, and retinal microvasculature. Additionally, transcription factor EB affects vascular smooth muscle cells, inhibiting vascular calcification and atherogenesis. In retinal pigment epithelial cells, transcription factor EB modulates functions such as autophagy, lysosomal dynamics, and clearance of the aging pigment lipofuscin, thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization. These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis, neuronal synapse plasticity, energy metabolism, microvasculature, and inflammation, ultimately offering protection against retinal aging and diseases. The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases. Therefore, it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

GdVO4:Eu3+ nanoparticles (OVNPs) have previously been shown to exhibit anti-aging effects in old rats.The accelerated aging model (overnutrition in early postnatal ontogenesis (POF)) was used to confirm the effect of OVNPs as a potential geroprotector. A comparative study of the effect of OVNPs, calorierestriction (CR) and CR-mimetic—metformin was carried out using a number of criteria: survival, prooxidant-antioxidant balance in the liver and blood, physiological parameters of male Wistar rats with accelerated aging. It was found that the survival of rats with POF was lower than that of control animals.It was found that the rate of superoxide radical formation and the content of lipid hydroperoxides in the mitochondria and microsomes of the liver and blood serum of rats with POF were higher, and the activities of glutathione peroxidases and the GSH content were significantly lower than in the control animals.It was also found that POF leads to perturbation of physiological parameters (body weight, liver weight, liver mass coefficient, body temperature and blood thyroxine concentration) characterizing the quality of life. Long-term use of OVNPs, CR or metformin in rats with accelerated aging normalized the imbalance of the prooxidant-antioxidant system, improved the physiological parameters, and increased the survival of these experimental animals. Moreover, the increase in survival was most pronounced with the use of CR and OVNPs. Considering our results andthe inadmissibility of long-term use of CR, it should be concluded that GdVO4:Eu3+ nanoparticles are promising for the development of agents that slow down the accelerated aging of an organism. [ABSTRACT FROM AUTHOR]

Abstract Background Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health risks. However, there is no consensus on the optimal regimen for weight management in adults. Methods We systematically searched PubMed, Embase, Web of Science, and Cochrane CENTRAL up to January 15, 2024, for randomized controlled trials (RCT) involving adults, evaluating the weight-loss effects of alternate day fasting (ADF), short-term fasting (STF), time-restricted eating (TRE), and continuous energy restriction (CER). The primary outcome was body weight, with secondary outcomes including BMI, fat mass, lean mass, waist circumference, fasting glucose, HOMA-IR, and adverse events. Bayesian network meta-analysis was conducted, ranking regimens using the surface under the cumulative ranking curve and the probability of being the best. Study quality was assessed using the Confidence in Network Meta-Analysis tool. Results Data from 47 RCTs (representing 3363 participants) were included. ADF showed the most significant body weight loss (Mean difference (MD): -3.42; 95% Confidence interval (CI): -4.28 to -2.55), followed by TRE (MD: -2.25; 95% CI: -2.92 to -1.59). STF (MD: -1.87; 95% CI: -3.32 to -0.56) and CER (MD: -1.59; 95% CI: -2.42 to -0.79) rank third and fourth, respectively. STF lead to decline in lean mass (MD: -1.26; 95% CI: -2.16, -0.47). TRE showed benefits on fasting glucose (MD: -2.98; 95% CI: -4.7, -1.26). Subgroup analysis revealed all four caloric restriction regimens likely lead to modest weight loss after 1–3 months, with ADF ranked highest, but by 4–6 months, varying degrees of weight regain occur, particularly with CER, while interventions lasting 7–12 months may result in effective weight loss, with TRE potentially ranking first during both the 4–6 months and 7–12 months periods. ADF showing fewer and shorter-lasting physical symptoms. Conclusion All four included regiments were effective in reducing body weight, with ADF likely having the most significant impact. Each regimen likely leads to modest weight loss after 1–3 months, followed by weight regain by 4–6 months. However, interventions lasting 7–12 months achieve greater weight loss overall. Trial registration PROSPERO: CRD42022382478.

Abstract Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population.

Background: Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood. Methods: FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations. Results: FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight. Conclusions: We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes. [ABSTRACT FROM AUTHOR]

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]

There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum , CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males. [Display omitted] • CYB5R3 overexpression reduces fat mass, enhances mitochondrial respiration, and boosts antioxidant protection in female mice. • There is a preferred utilization of fatty acids as an energy source in females overexpressing CYB5R3. • CYB5R3 overexpression is phenotypic closer to calorie restriction in females than in males. • CYB5R3 overexpression plus CR maintain mitochondrial abundance and activity in skeletal muscle and liver of female mice. • Calorie restriction and CYB5R3 overexpression crosstalk exhibits sexual dimorphism. [ABSTRACT FROM AUTHOR]

Introduction Studies link hypovitaminosis D to be significantly associated with poor glycemic control, heightened inflammation, and risk of complications. Studies recommend fasting or calorie restriction as a useful measure to achieve diabetic reversal. The present study explores if therapeutic fasting is associated with improvement in the vitamin D levels and other clinical outcomes related to type 2 diabetes mellitus (T2DM). Methods This observational study included 26 T2DM patients exposed to a 10-day medically supervised fasting (≈ 500–1000 Kcal/day) in a complementary medicine facility. Levels of vitamin D, B12, fasting blood sugar (FBS), blood pressure, anthropometric measures, World Health Organization Quality of Life, disease perception (Brief Illness Perception Questionnaire), and self-reported vitality were measured at the baseline and the 10th day. Results Significant improvement in the levels of vitamin D (p = 0.000), B12 (p = 0.03), and reduction in FBS levels (p = 0.001), blood pressure, body mass index, waist and hip circumference (p ≤ 0.05), and improvement in quality of life, vitality, and disease perception (p < 0.001) were observed by the end of 10th day. FBS shared a negative correlation with vitamin D levels (males r = –0.1, females r = –0.48). Conclusion The present findings provide insights into the probable mechanisms by which therapeutic fasting modulates the progression of T2DM. Nevertheless, large-scale randomized controlled trials are warranted to validate the present findings. [ABSTRACT FROM AUTHOR]

The population around the world is graying, and as many of these individuals will spend years suffering from the burdens of age associated diseases, understanding how to increase healthspan, defined as the period of life free from disease and disability, is an urgent priority of geroscience research. The lack of agreed-upon quantitative metrics for measuring healthspan in aging mice has slowed progress in identifying interventions that do not simply increase lifespan, but also healthspan. Here, we define FAMY (Frailty-Adjusted Mouse Years) and GRAIL (Gauging Robust Aging when Increasing Lifespan) as new summary statistics for quantifying healthspan in mice. FAMY integrates lifespan data with longitudinal measurements of a widely utilized clinical frailty index, while GRAIL incorporates these measures and also adds information from widely utilized healthspan assays and the hallmarks of aging. Both metrics are conceptually similar to quality-adjusted life years (QALY), a widely utilized measure of disease burden in humans, and can be readily calculated from data acquired during longitudinal and cross-sectional studies of mouse aging. We find that interventions generally thought to promote health, including calorie restriction, robustly improve healthspan as measured by FAMY and GRAIL. Finally, we show that the use of GRAIL provides new insights, and identify dietary restriction of protein or isoleucine as interventions that robustly promote healthspan but not longevity in female HET3 mice. We suggest that the routine integration of these measures into studies of aging in mice will allow the identification and development of interventions that promote healthy aging even in the absence of increased lifespan. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)–fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p<0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p<0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health risks. However, there is no consensus on the optimal regimen for weight management in adults. Methods: We systematically searched PubMed, Embase, Web of Science, and Cochrane CENTRAL up to January 15, 2024, for randomized controlled trials (RCT) involving adults, evaluating the weight-loss effects of alternate day fasting (ADF), short-term fasting (STF), time-restricted eating (TRE), and continuous energy restriction (CER). The primary outcome was body weight, with secondary outcomes including BMI, fat mass, lean mass, waist circumference, fasting glucose, HOMA-IR, and adverse events. Bayesian network meta-analysis was conducted, ranking regimens using the surface under the cumulative ranking curve and the probability of being the best. Study quality was assessed using the Confidence in Network Meta-Analysis tool. Results: Data from 47 RCTs (representing 3363 participants) were included. ADF showed the most significant body weight loss (Mean difference (MD): -3.42; 95% Confidence interval (CI): -4.28 to -2.55), followed by TRE (MD: -2.25; 95% CI: -2.92 to -1.59). STF (MD: -1.87; 95% CI: -3.32 to -0.56) and CER (MD: -1.59; 95% CI: -2.42 to -0.79) rank third and fourth, respectively. STF lead to decline in lean mass (MD: -1.26; 95% CI: -2.16, -0.47). TRE showed benefits on fasting glucose (MD: -2.98; 95% CI: -4.7, -1.26). Subgroup analysis revealed all four caloric restriction regimens likely lead to modest weight loss after 1–3 months, with ADF ranked highest, but by 4–6 months, varying degrees of weight regain occur, particularly with CER, while interventions lasting 7–12 months may result in effective weight loss, with TRE potentially ranking first during both the 4–6 months and 7–12 months periods. ADF showing fewer and shorter-lasting physical symptoms. Conclusion: All four included regiments were effective in reducing body weight, with ADF likely having the most significant impact. Each regimen likely leads to modest weight loss after 1–3 months, followed by weight regain by 4–6 months. However, interventions lasting 7–12 months achieve greater weight loss overall. Trial registration: PROSPERO: CRD42022382478. [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]

Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence? [ABSTRACT FROM AUTHOR]

Introduction: Calorie restriction is a nutritional intervention by reducing energy intake. The purpose of the current study was the effect of 8 weeks of HIIT training with calorie restriction of standard diet and high fat diet on the expression of BDH1 and ACAT1 genes in the liver of healthy male Wistar rats. Methods & Materials: 48 male rats were randomly divided into 6 groups (n=8): control, exercise, calorie restriction of high-fat diet, calorie restriction of standard diet, calorie restriction of standard diet + exercise, and calorie restriction of high-fat diet + exercise It was performed for 8 weeks (5 days a week) with an intensity of 100-90% of the maximum speed in the form of running on a treadmill with a zero-degree slope and in the morning (9 o'clock). Expression of BDH1 and ACAT1 genes in liver tissue was measured by Real Time-PCR method and one-way analysis of variance statistical method was used for comparison between groups. Results: Exercise caused a significant increase in BDH1 gene expression compared to the control group (P<0.001). Simultaneous training with high-fat diet calorie restriction and standard diet calorie restriction led to a significant increase in BDH1 and ACAT1 gene expression compared to the control group (P<0.001). Conclusion: In the conditions of calorie restriction, high-intensity interval training through the upregulation of BDH1 and ACAT1 gene expression may play a key role in increasing hepatic gluconeogenesis. Also, high-intensity interval training through the upregulation of the BDH1 gene can have play an important role in hepatic fat oxidation. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia. This study utilized post-mortem brain tissue from rhesus monkeys that died after decades on a 30 % reduced calorie diet. We found that CR subjects had significantly fewer cells with oxidative damage within the corpus callosum and the cingulum bundle. Oligodendrocytes specifically showed the greatest response to CR with a robust reduction in DNA damage. Additionally, we observed alterations in microglia morphology with CR subjects having a higher proportion of ramified, homeostatic microglia and fewer pro-inflammatory, hypertrophic microglia relative to controls. Furthermore, we determined that the observed attenuation in damaged DNA occurs primarily within mitochondria. Overall, these data suggest that long-term CR can reduce oxidative DNA damage and offer a neuroprotective effect in a cell-type-specific manner in the aging monkey brain. • Long-term CR in aging monkeys reduces oxidative DNA damage in oligodendrocytes. • DNA damage in oligodendrocytes of aging monkeys is primarily within mitochondria. • Long-term CR does not alter baseline DNA damage in microglia. • Long-term CR promotes ramified microglia and reduces hypertrophic / ameboid phenotypes. [ABSTRACT FROM AUTHOR]

Background: Although Calorie Restriction (CR) is primarily considered in obesity management, behavioral studies of CR and its methodology of implementation are not well-defined. Objective: The study aimed to determine the efficacy of the extensively researched method of CR—abrupt calorie restriction (ACR) and a newly proposed gradual calorie restriction (GCR) in terms of body weight, behavioral and biochemical parameters in the obese animal model—C57BL/6J mice. Design: Male obese mice were subjected to GCR regimen for 14 weeks which was compared and evaluated for anxiety-like behavior and stress levels with ACR. Plasma corticosterone was measured before initiation of CR and every three weeks following GCR and ACR, whereas plasma insulin was measured twice—after obesity induction and post 14 weeks of CR. The behavioral assessments were conducted before inducing CR and every three weeks following ACR and GCR. Results: A significant anxiety-like behavior and an increase in plasma corticosterone were observed in mice on GCR during the critical initial six weeks of CR (p < 0.05). Both groups showed a decrease in plasma glucose levels; however, the GCR group showed a significant reduction (p < 0.01). There was a significant decrease in social interaction in both groups with an increase in the latency period and a decrease in time spent with the stranger animal during the social interaction test (p < 0.05). Conclusion: The mice on GCR regimen demonstrated lesser anxiety-like behavior and low plasma corticosterone levels compared to those on ACR. This gives us a new avenue in CR research to evaluate the methodologies of implementing CR. [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]

Summary: A systematic review and meta‐analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random‐effects meta‐analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta‐regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: −4.11 to −0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [−2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses. [ABSTRACT FROM AUTHOR]

The present review has mainly focused on a systematic investigation of the genes responsible for biological ageing. Ageing has been defined as a successive decline in biological functions, leading to age-associated disorders, which have caused death. Cell homeostasis has been disturbed due to multiple factors such as accumulation of DNA damage, decrease in telomeres, replicative senescence, cell division, metabolism, respiration, autophagy, calorie management, and genetic integrity. This imbalance in cell homeostasis has a major impact on the accelerated biological ageing process. Increased risk of age-associated disorders and mortality rates makes it necessary to know the cellular and molecular mechanisms behind it. This current study provides an overview of genes and their functions associated with dysregulation in core cellular functions such as replication, genetic stability, metabolism, respiration, and autophagy. The genes associated with these biological processes have been identified through a comprehensive literature survey and additional genes were included based on the outcome of STRING analysis. These genes were functionally enriched using gene ontology. Finally, a selected set of genes was mapped with 74 biological functions. Then, a correlation map was plotted to bring out genes with maximum impact on the biological processes involved in ageing. This study not only observed the most commonly known players such as mTOR and SIRT1 but also noticed less-reported genes such as ATM, LRRK2, ERCC1, ATG5, and BECN1 which were also found to be highly impacting the process of biological ageing. Additionally, the gerontology of these top five less-reported genes also has been explored. [ABSTRACT FROM AUTHOR]

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population. [ABSTRACT FROM AUTHOR]

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension.

ABSTRACT For decades, the prevailing assumption in the field of eating disorders has been that dietary restraint causes weight gain and eating disorder symptoms, like binge eating. This belief resulted in widespread recommendations to reduce dietary restraint in treatments of eating disorders and obesity. However, recent findings by Grilo and Pittman (2024; International Journal of Eating Disorders xxx:xxxx–xxxx) contradict this view, showing reduced binge frequency and greater weight loss with increased rigid dietary restraint. This commentary critically evaluates the evidence supporting a causal link between dietary restraint and overeating, highlighting the limitations of longitudinal and observational studies and the misinterpretations of early laboratory research. Importantly, randomized controlled trials and experiments that directly manipulate calorie intake show that calorie restriction improves eating control and reduces eating disorder symptoms. Conceptual issues are discussed; self‐reported dietary restraint is not an accurate reflection of actual calorie restriction. It is argued that cognitive processes like learned food cue reactivity, weak executive skills and increased reward sensitivity can explain tendencies to overeat. They are usually followed by attempts to restrain food intake—essentially reverse causality. It is further hypothesized that the eating of healthy whole foods while avoiding unhealthy ultra‐processed foods, could benefit both the prevention and treatment of all eating and weight disorders. [ABSTRACT FROM AUTHOR]

Intermittent fasting (IF) and calorie restriction (CR) were purported to have health benefits. This research aimed to determine the long-term effect of IF and CR on selected neurological parameters in mice. Swiss Webster male mice were divided into 3 groups: ad libitum feeding (AL), IF, and CR. Mice in each group received the treatment for 16 weeks. They were then tested for anhedonia, depression, aggressiveness, and social approach. They were also subjected to contextual fear conditioning tests to model PTSD. Compared to AL, sucrose intake in the IF group was lower, while the CR group showed higher intake (p

This study aims to analyze the level of stress oxidative with treatment calorie restrictions and administration of sucrose solution. This study was a laboratory experimental study with 12 male white rats (Wistar strain) as subjects for caloric restrictive treatment and 12 rats for 50% sucrose solution. Where each group of rats is determined by the dependent and independent variables. Using the pre-posttest control design, the dependent variable of caloric restriction, and the independent variable malondialdehyde. The dependent variables used were body weight using a scale, fasting blood glucose using a glucometer, and MDA using a UV-Vis spectrophotometer. The independent variable used was the administration of 50% sucrose solution. The data were statistically analyzed by T-test analysis. There was no significant decrease in MDA levels in the caloric restriction treatment rats (p = 0.060), besides that there was a significant difference in body weight in both the control and sucrose groups (p 0.05) and there was a significant difference in the sucrose group (p < 0.05). There was no significant difference in serum MDA levels in either the control or sucrose groups (p > 0.05). There is an effect of calorie restriction on MDA levels. Also, administration of 50% sucrose solution for 4 weeks had a significant effect on the rats' body weight and blood glucose but did not have a significant effect on serum MDA levels.

Abstract We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20–25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET.

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]

Background: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-β1), and other indicators in the presence and absence of ovaries in AKI female rats. Methods: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. Results: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin. Conclusion: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-β1 in ovary-intact animals. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody and/or thyroglobulin antibody. In recent decades, HT disease has become more and more widespread. Patients always report multiple symptoms, even though their thyroid hormone levels are kept in normal ranges. However, no treatment exists to effectively reduce the levels of thyroid antibodies. Our study aims to determine whether calorie-restricted diet is helpful in improving health of HT patients. Methods and Study Design: This is a 3-month randomized controlled trial. HT patients will be randomized into a calorie-restricted (CR) group or a calorie-unrestricted control group. All the participants will be instructed to consume a diet that includes a combination of 45-55% calories from carbohydrates, 20-30% from fats, and 15- 25% from proteins, according to current Chinese Dietary Guidelines. Participants in CR group need to limit their calories intake equal to their basal energy expenditure, which means that their daily caloric intake will be limited by about 20-30%. Results: The study population is planned to be 66 HT patients aged 18 to 65 years. The primary outcome is change of thyroid antibody levels from baseline. Secondary outcomes include the changes of nonhypothyroid symptoms scores, thyroid function indexes, morphology of thyroid, T lymphocyte subpopulations, inflammatory biomarkers and lipids from baseline to 12 weeks. Conclusions: This trial will have implications for nutrition treatment policy in regard to thyroid antibodies control, immune dysfunction and related nonhypothyroid symptoms improvement among HT patients. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co‐release the agouti‐related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPY neurons regulate several hypothalamic–pituitary‐endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPY neurons on the pattern of GH secretion in fed and food‐deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPY neurons (AgRP∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHR mice. Our findings indicate that short‐term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPY neurons. [ABSTRACT FROM AUTHOR]

Background: Human aging is often associated with diseases that limit quality of life. Therapeutic anti-aging interventions, such as calorie restriction, can slow its progression. Analyzing the main areas of interest in the scientific literature allows us to understand the trends in research on calorie restriction in aging. This research aimed to conduct a comprehensive bibliometric analysis to determine the approaches and areas of research activity related to studying calorie restriction in aging and its use as a therapeutic intervention to slow its development. Methods: A bibliometric analysis was conducted based on publications deposited in Scopus using its API and VOSViewer. Results: A total of 5565 published documents were reviewed. The main keywords were analyzed and grouped into five study groups: risk factors and pathological consequences, biochemical mechanisms linked to caloric restriction and aging, experimental issues and clinical studies, functional aspects of the cell and caloric restriction, and his experimental study. The study shows the trend of increasing publications. Most of these articles are written in English and published in the United States. Conclusions: Calorie restriction in aging is a topic of interest to researchers, and more research is needed to improve its understanding and therapeutic application. [ABSTRACT FROM AUTHOR]

We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20–25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET. [ABSTRACT FROM AUTHOR]

Professor Sataro Goto is one of the pioneers of biological aging research in Japan. He is renowned for his work on the role of protein errors and modifications, the accumulation of abnormal proteins due to reduced protein turnover, and the modulation of aging and lifespan by adult-onset dietary restriction and regular exercise. Professor Goto is a remarkably intelligent, visionary, empathetic, humble, and wise man, who kindly agreed to this interview that I (Zsolt Radak) made with him during one of my frequent visits to his labs, in February 2023. [ABSTRACT FROM AUTHOR]

Aging is linked to a time-associated decline in both cellular function and repair capacity leading to malfunction on an organismal level, increased frailty, higher incidence of diseases, and death. As the population grows older, there is a need to reveal mechanisms associated with aging that could spearhead treatments to postpone the onset of age-associated decline, extend both healthspan and lifespan. One possibility is targeting the sirtuin SIRT1, the founding member of the sirtuin family, a highly conserved family of histone deacetylases that have been linked to metabolism, stress response, protein synthesis, genomic instability, neurodegeneration, DNA damage repair, and inflammation. Importantly, sirtuins have also been implicated to promote health and lifespan extension, while their dysregulation has been linked to cancer, neurological processes, and heart disorders. SIRT1 is one of seven members of sirtuin family; each requiring nicotinamide adenine dinucleotide (NAD+) as cosubstrate for their catalytic activity. Overexpression of yeast, worm, fly, and mice SIRT1 homologs extend lifespan in each animal, respectively. Moreover, lifespan extension due to calorie restriction are associated with increased sirtuin activity. These findings led to the search for a calorie restriction mimetic, which revealed the compound resveratrol; (3, 5, 4'-trihydroxy-trans-stilbene) belonging to the stilbenoids group of polyphenols. Following this finding, resveratrol and other sirtuin-activating compounds have been extensively studied for their ability to affect health and lifespan in a variety of species, including humans via clinical studies. [ABSTRACT FROM AUTHOR]

BackgroundMaternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.MethodsFGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations.ResultsFGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight.ConclusionsWe demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.

IntroductionIntermittent fasting (IF) has been reported to be involved in ameliorating oxidative stress and lessening the systemic-low grade inflammation that predisposes to chronic diseases. Gene polymorphism is currently a main determining factor for the metabolic responses to different dietary and lifestyle modifications.MethodsThe current study was designed to explore the effect of observing four-week, dawn to dusk IF by participants with obesity on gene expression of the anti-inflammatory CD163, oxidative stress, and bioenergetics enzymes (SOD2, Nrf2, and TFAM), as well as metabolic and cellular regulatory genes (SIRT1 and SIRT3). Further, the study aimed to find out how haptoglobin (Hp) polymorphism modulates gene expression of the aforementioned genes and to determine changes in relative gene expressions of the aforementioned six genes based on Hp polymorphism in response to IF. Haptoglobin genotype was determined for the study subjects, and gene expressions were determined using qPCR. Gene expressions were assessed before and at the end of four consecutive weeks, dawn to sunset IF.ResultsThe expressions of CD163, SOD, NfF2, and TFAM genes have significantly increased at the end of IF. At the same time, SIRT3 significantly decreased, implying that observing four consecutive weeks of dawn-to-dusk IF may enhance antioxidative stress response and reduce systemic inflammation.ConclusionParticipants with genotypes Hp2-1 and Hp2-2 revealed upregulation of the antioxidant genes in response to the metabolic stress induced by IF compared with Hp1-1, implying that Hp polymorphism plays a key role in shaping the body’s response to dietary modifications such as fasting.

ObjectiveBoth 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.MethodsThis single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).ResultsIn comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p 0.05).ConclusionIn summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence?