Special Issue "Calorie Restriction’s Effects on Health and Disease: From Basic Research to Human Health"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Carbohydrates".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editor

Prof. Dr. Takuya Chiba
E-Mail Website
Guest Editor
Biomedical Gerontology Laboratory, Faculty of Human Sciences, Waseda University, Japan
Interests: biology of aging; longevity science; calorie restriction mimetics; food factor

Special Issue Information

Dear Colleagues,

Calorie restriction is one of the most viable interventions to help reduce morbidity from age-related diseases and to increase healthy lifespans and longevity. The term itself implies various forms of nutritional interventions, such as reducing total caloric intake, reducing macronutrients, and temporal limitation of food intake, in ways that include intermittent fasting and limiting eating periods. Recently, calorie restriction mimetics, which imitate the health benefits of calorie restriction without actual food intake restriction, have been attracting attention for use in nutritional interventions and drug development to support healthy lives.

In this Special Issue of Nutrients, we focus on the study of calorie restriction in basic research on animals, as well as clinical application in research that affects humans. Recent tools for high-throughput research instruments can investigate and determine critical signaling pathways and identify responsible molecules for the life-extending effects of calorie restriction. Potential candidates for calorie restriction mimetics are also extensively explored and verified through the use of cells, mice, and even humans. Additionally, we offer discussion on the immune system and inflammation concerning aging during calorie restriction.

This Special Issue is dedicated to increasing and renewing our knowledge of the effects of calorie restriction on age-related diseases and longevity-oriented guidelines. We expect that this issue will improve our understanding of recent advances in calorie restriction research for researchers from many fields of expertise. We welcome a variety of manuscript submissions, including original research, short reports, and reviews

Prof. Takuya Chiba
Guest Editor

Manuscript Submission Information

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Keywords

  • Calorie restriction mimetics
  • Immunosenescence
  • Inflammaging
  • Inter-organ communication
  • Ketone body

Published Papers (8 papers)

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Research

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Article
A Comparison of Gene Expression Profiles of Rat Tissues after Mild and Short-Term Calorie Restrictions
Nutrients 2021, 13(7), 2277; https://doi.org/10.3390/nu13072277 - 30 Jun 2021
Viewed by 643
Abstract
Many studies have shown the beneficial effects of calorie restriction (CR) on rodents’ aging; however, the molecular mechanism explaining these beneficial effects is still not fully understood. Previously, we conducted transcriptomic analysis on rat liver with short-term and mild-to-moderate CR to elucidate its [...] Read more.
Many studies have shown the beneficial effects of calorie restriction (CR) on rodents’ aging; however, the molecular mechanism explaining these beneficial effects is still not fully understood. Previously, we conducted transcriptomic analysis on rat liver with short-term and mild-to-moderate CR to elucidate its early response to such diet. Here, we expanded transcriptome analysis to muscle, adipose tissue, intestine, and brain and compared the gene expression profiles of these multiple organs and of our previous dataset. Several altered gene expressions were found, some of which known to be related to CR. Notably, the commonly regulated genes by CR include nicotinamide phosphoribosyltransferase and heat shock protein 90, which are involved in declining the aging process and thus potential therapeutic targets for aging-related diseases. The data obtained here provide information on early response markers and key mediators of the CR-induced delay in aging as well as on age-associated pathological changes in mammals. Full article
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Article
Fasting: How to Guide
Nutrients 2021, 13(5), 1570; https://doi.org/10.3390/nu13051570 - 07 May 2021
Viewed by 9894
Abstract
Fasting potentials are the most interesting topics in the Nutritional Era. Fasting consists of the catabolism of lipids, proteins, and carbohydrates to maintain blood glucose levels in a normal range. The action mechanisms of fasting were firstly understood in minor organisms and later [...] Read more.
Fasting potentials are the most interesting topics in the Nutritional Era. Fasting consists of the catabolism of lipids, proteins, and carbohydrates to maintain blood glucose levels in a normal range. The action mechanisms of fasting were firstly understood in minor organisms and later in humans. Nutritional interventions of caloric restriction could attenuate age-associated epigenetic alterations and could have a protective effect against cellular alterations, promoting longevity and health span. While most fasting studies point out the weight and fat mass decreases, it is important to define specific guidelines for fasting and non-fasting days to enhance adherence, minimize the dropout rates of the interventions, and maximize body composition improvement. Although the panorama of evidence on fasting and caloric restriction is wide, there is a lack of a safe fasting protocol to guide physicians in its prescription. The main goal is to identify a how to use guide, a major posology of fasting, inserted within a huge dietetic personalized strategy leading to an optimal and healthy nutritional status. Full article
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Article
Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice
Nutrients 2021, 13(3), 985; https://doi.org/10.3390/nu13030985 - 18 Mar 2021
Cited by 1 | Viewed by 764
Abstract
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is [...] Read more.
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology. Full article
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Article
Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus
Nutrients 2021, 13(1), 232; https://doi.org/10.3390/nu13010232 - 15 Jan 2021
Viewed by 788
Abstract
Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast [...] Read more.
Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here. Full article
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Review

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Review
Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet
Nutrients 2021, 13(4), 1302; https://doi.org/10.3390/nu13041302 - 15 Apr 2021
Viewed by 2906
Abstract
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting [...] Read more.
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches. Full article
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Review
Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm
Nutrients 2020, 12(11), 3476; https://doi.org/10.3390/nu12113476 - 12 Nov 2020
Cited by 2 | Viewed by 1119
Abstract
The circadian rhythm plays a chief role in the adaptation of all bodily processes to internal and environmental changes on the daily basis. Next to light/dark phases, feeding patterns constitute the most essential element entraining daily oscillations, and therefore, timely and appropriate restrictive [...] Read more.
The circadian rhythm plays a chief role in the adaptation of all bodily processes to internal and environmental changes on the daily basis. Next to light/dark phases, feeding patterns constitute the most essential element entraining daily oscillations, and therefore, timely and appropriate restrictive diets have a great capacity to restore the circadian rhythm. One of the restrictive nutritional approaches, caloric restriction (CR) achieves stunning results in extending health span and life span via coordinated changes in multiple biological functions from the molecular, cellular, to the whole–body levels. The main molecular pathways affected by CR include mTOR, insulin signaling, AMPK, and sirtuins. Members of the family of nuclear receptors, the three peroxisome proliferator–activated receptors (PPARs), PPARα, PPARβ/δ, and PPARγ take part in the modulation of these pathways. In this non-systematic review, we describe the molecular interconnection between circadian rhythm, CR–associated pathways, and PPARs. Further, we identify a link between circadian rhythm and the outcomes of CR on the whole–body level including oxidative stress, inflammation, and aging. Since PPARs contribute to many changes triggered by CR, we discuss the potential involvement of PPARs in bridging CR and circadian rhythm. Full article
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Review
Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?
Nutrients 2020, 12(7), 1959; https://doi.org/10.3390/nu12071959 - 30 Jun 2020
Viewed by 1617
Abstract
Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of [...] Read more.
Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of growth hormone (GH)–insulin-like growth factor (IGF)-1 signaling, in an isoform-specific manner. Inflammaging is a term coined to represent that persistent low-level of inflammation underlies the progression of aging and related diseases. Attenuation of inflammaging in the body may underlie the effects of CR. Recent studies have also identified cellular senescence and activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome as causative factors of inflammaging. In this paper, we reviewed the current knowledge of the molecular mechanisms linking the effects of CR with the formation of inflammasomes, particularly focusing on possible relations with FoxO3. Inflammation in the brain that affects adult neurogenesis and lifespan was also reviewed as evidence of inflammaging. A recent progress of microRNA research was described as regulatory circuits of initiation and propagation of inflammaging. Finally, we briefly introduced our preliminary results obtained from the mouse models, in which Foxo1 and Foxo3 genes were conditionally knocked out in the myeloid cell lineage. Full article
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Other

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Brief Report
Alternate Day Fasting Combined with a Low Carbohydrate Diet: Effect on Sleep Quality, Duration, Insomnia Severity and Risk of Obstructive Sleep Apnea in Adults with Obesity
Nutrients 2021, 13(1), 211; https://doi.org/10.3390/nu13010211 - 13 Jan 2021
Viewed by 1494
Abstract
Background: Alternate day fasting combined with a low carbohydrate diet (ADF-LC) is an effective weight loss regimen. Whether the weight loss induced by ADF-LC can improve sleep, remains unknown. Objective: This study examined the effect an ADF-LC diet on sleep quality, duration, [...] Read more.
Background: Alternate day fasting combined with a low carbohydrate diet (ADF-LC) is an effective weight loss regimen. Whether the weight loss induced by ADF-LC can improve sleep, remains unknown. Objective: This study examined the effect an ADF-LC diet on sleep quality, duration, insomnia severity and the risk of obstructive sleep apnea. Methods: Adults with obesity (n = 31) participated in ADF (600 kcal “fast day”; ad libitum intake “feast day”) with a low-carbohydrate diet (30% carbohydrates, 35% protein, and 35% fat). The 6-month trial consisted of a 3-month weight loss period followed by a 3-month weight maintenance period. Results: Reductions in body weight (−5 ± 1 kg, p < 0.001) and fat mass (−4 ± 1 kg, p < 0.01) were noted during the weight loss period, and these reductions were sustained during the weight maintenance period. Lean mass and visceral fat remained unchanged. The Pittsburgh Sleep Quality Index (PSQI) score indicated poor sleep quality at baseline (6.4 ± 0.7) with no change by month 3 or 6, versus baseline. ISI score indicated subthreshold insomnia at baseline (8.5 ± 1.0), with no change by month 3 or 6, versus baseline. The percent of subjects with high risk of obstructive sleep apnea at baseline was 45%, with no change by month 3 or 6. Wake time, bedtime, and sleep duration remained unchanged. Conclusion: The ADF-LC diet does not impact sleep quality, duration, insomnia severity or the risk of obstructive sleep apnea in adults with obesity. Full article
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