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The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease

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

Deadline for manuscript submissions: closed (15 March 2020) | Viewed by 85695

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Prof. Hae-Young Chung

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Biochemistry Lab., College of Pharmacy, Pusan Nation University, Busan 46241, Korea

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Dear Colleagues,

Recent biochemical studies indicate that calorie restriction (CR) is a widely accepted method for anti-aging intervention. CR and intermittent fasting (IF), which involves reduced calories but proper nutritional intake during specific periods, are interventions that can consistently promote health benefits, delay biological aging, and extend both average and maximal lifespan. Furthermore, CR can modulate age-related diseases such as Alzheimer’s disease, atherosclerosis, diabetes, obesity, cancer, and others.

Advances in omics technologies have provided a technical breakthrough that enables the investigation of DNA, RNA, proteins, and other cellular molecules and their comprehensive interactions in a biological context. Nowadays, it is possible to analyze and integrate biological processes that occur in aging systems at the molecular level using state-of-the-art techniques such as next-generation sequencing (NGS), proteomics, lipidomics, metabolomics, and epigenomics. Omics technologies and approaches analyze and provide predictive information on CR effects, molecular mechanisms, and pathways.

This Special Issue, “The effect of calorie restriction and intermittent fasting on health and disease”, focuses on the effects of calorie restriction and intermittent fasting on age-related inflammation, autophagy, metabolism, longevity, cancer, mitochondrial function, and age-related diseases.

Prof. Hae-Young Chung
Guest Editor

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Keywords

Calorie restriction
Intermittent fasting
Age-related diseases
Metabolism
Omics
Mitochondria
Autophagy
Inflammation

Published Papers (10 papers)

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Editorial

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5 pages, 182 KiB

Open AccessEditorial

Impacts of Calorie Restriction and Intermittent Fasting on Health and Diseases: Current Trends

by Hae Young Chung, Dae Hyun Kim, EunJin Bang and Byung Pal Yu

Nutrients 2020, 12(10), 2948; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12102948 - 25 Sep 2020

Cited by 7 | Viewed by 5475

Abstract

This special issue on the effects of calorie restriction (CR) and intermittent fasting (IF) on health and diseases includes five scholarly reviews and four original articles that provide an insight into the molecular and cellular action mechanisms of epigenetically manipulated dietary paradigms [...] [...] Read more.

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

Research

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15 pages, 3671 KiB

Open AccessArticle

Srebp-1c/Fgf21/Pgc-1α Axis Regulated by Leptin Signaling in Adipocytes—Possible Mechanism of Caloric Restriction-Associated Metabolic Remodeling of White Adipose Tissue

by Masaki Kobayashi, Seira Uta, Minami Otsubo, Yusuke Deguchi, Ryoma Tagawa, Yuhei Mizunoe, Yoshimi Nakagawa, Hitoshi Shimano and Yoshikazu Higami

Nutrients 2020, 12(7), 2054; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12072054 - 10 Jul 2020

Cited by 19 | Viewed by 3922

Abstract

Caloric restriction (CR) improves whole body metabolism, suppresses age-related pathophysiology, and extends lifespan in rodents. Metabolic remodeling, including fatty acid (FA) biosynthesis and mitochondrial biogenesis, in white adipose tissue (WAT) plays an important role in the beneficial effects of CR. We have proposed that CR-induced mitochondrial biogenesis in WAT is mediated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is transcriptionally regulated by sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA biosynthesis. We have also proposed that the CR-associated upregulation of SREBP-1 and PGC-1α might result from the attenuation of leptin signaling and the upregulation of fibroblast growth factor 21 (FGF21) in WAT. However, the detailed molecular mechanisms remain unclear. Here, we interrogate the regulatory mechanisms involving leptin signaling, SREBP-1c, FGF21, and PGC-1α using Srebp-1c knockout (KO) mice, mouse embryonic fibroblasts, and 3T3-L1 adipocytes, by altering the expression of SREBP-1c or FGF21. We show that a reduction in leptin signaling induces the expression of proteins involved in FA biosynthesis and mitochondrial biogenesis via SREBP-1c in adipocytes. The upregulation of SREBP-1c activates PGC-1α transcription via FGF21, but it is unlikely that the FGF21-associated upregulation of PGC-1α expression is a predominant contributor to mitochondrial biogenesis in adipocytes. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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24 pages, 4623 KiB

Open AccessArticle

Intermittent Fasting for Twelve Weeks Leads to Increases in Fat Mass and Hyperinsulinemia in Young Female Wistar Rats

by Ana Cláudia Munhoz, Eloisa Aparecida Vilas-Boas, Ana Carolina Panveloski-Costa, Jaqueline Santos Moreira Leite, Camila Ferraz Lucena, Patrícia Riva, Henriette Emilio and Angelo R. Carpinelli

Nutrients 2020, 12(4), 1029; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12041029 - 09 Apr 2020

Cited by 18 | Viewed by 8156

Abstract

Fasting is known to cause physiological changes in the endocrine pancreas, including decreased insulin secretion and increased reactive oxygen species (ROS) production. However, there is no consensus about the long-term effects of intermittent fasting (IF), which can involve up to 24 hours of fasting interspersed with normal feeding days. In the present study, we analyzed the effects of alternate-day IF for 12 weeks in a developing and healthy organism. Female 30-day-old Wistar rats were randomly divided into two groups: control, with free access to standard rodent chow; and IF, subjected to 24-hour fasts intercalated with 24-hours of free access to the same chow. Alternate-day IF decreased weight gain and food intake. Surprisingly, IF also elevated plasma insulin concentrations, both at baseline and after glucose administration collected during oGTT. After 12 weeks of dietary intervention, pancreatic islets displayed increased ROS production and apoptosis. Despite their lower body weight, IF animals had increased fat reserves and decreased muscle mass. Taken together, these findings suggest that alternate-day IF promote β -cell dysfunction, especially in developing animals. More long-term research is necessary to define the best IF protocol to reduce side effects. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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12 pages, 2542 KiB

Open AccessArticle

Myocardial Dysfunction after Severe Food Restriction Is Linked to Changes in the Calcium-Handling Properties in Rats

by Adriana Fernandes de Deus, Vítor Loureiro da Silva, Sérgio Luiz Borges de Souza, Gustavo Augusto Ferreira Mota, Paula Grippa Sant’Ana, Danielle Fernandes Vileigas, Ana Paula Lima-Leopoldo, André Soares Leopoldo, Dijon Henrique Salomé de Campos, Loreta Casquel de Tomasi, Carlos Roberto Padovani, Stephen C. Kolwicz, Jr. and Antonio Carlos Cicogna

Nutrients 2019, 11(9), 1985; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11091985 - 22 Aug 2019

Cited by 6 | Viewed by 4287

Abstract

Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca²⁺-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar–Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca²⁺ and in the absence or presence of a sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) specific blocker. The expression of Ca²⁺-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca²⁺ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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14 pages, 583 KiB

Open AccessArticle

Six Weeks of Calorie Restriction Improves Body Composition and Lipid Profile in Obese and Overweight Former Athletes

by Joanna Hołowko, Małgorzata Magdalena Michalczyk, Adam Zając, Maja Czerwińska-Rogowska, Karina Ryterska, Marcin Banaszczak, Karolina Jakubczyk and Ewa Stachowska

Nutrients 2019, 11(7), 1461; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11071461 - 27 Jun 2019

Cited by 27 | Viewed by 4866

Abstract

Objective: The aim of the study was to compare the impact of 6 weeks of reducing daily caloric intake by 20% of total daily energy expenditure (TDEE)-CRI vs. reducing daily caloric intake by 30% of TDEE-CRII on body mass reduction and insulin metabolism in former athletes. Methods: 94 males aged 35.7 ± 5.3 years, height 180.5 ± 4.1 cm, and body mass 96.82 ± 6.2 kg were randomly assigned to the CRI (n = 49) or CRII (n = 45) group. Thirty-one participants (18 subjects from CRI and 13 from CRII) resigned from the study. The effects of both diets on the body composition variables (body mass—BM; body fat—BF; fat free mass—FFM; muscle mass—MM; total body water—TBW), lipid profile (total lipids—TL; total cholesterol—TCh; HDL cholesterol—HDL; LDL cholesterol—LDL; triglycerides—TG), and glucose control variables (glucose—GL, insulin—I, HOMA-IR, insulin-like growth factor-1—IGF-1, leptin and adiponectin) were measured. Results: After adhering to the CR I diet, significant differences were observed in FFM, MM and TG. After adhering to the CR II diet, significant differences were registered in tCh, TL and LDL. Both diets had a significant influence on leptin and adiponectin concentrations. Significant differences in FFM, MM, and tCh were observed between the CR I and CR II groups. At the end of the dietary intervention, significant differences in BF, FFM, MM and TBW were observed between the CR I and CR II groups. Conclusion: The 6 weeks of CR II diet appeared to be more effective in reducing BF and lipid profile and proved to be especially suitable for subjects with high body fat content and an elevated level of lipoproteins and cholesterol. Both reductive diets were effective in improving the levels of leptin and adiponectin in obese former athletes. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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Review

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18 pages, 849 KiB

Open AccessReview

Shedding Light on the Effects of Calorie Restriction and Its Mimetics on Skin Biology

by Yeon Ja Choi

Nutrients 2020, 12(5), 1529; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12051529 - 24 May 2020

Cited by 10 | Viewed by 6515

Abstract

During the aging process of an organism, the skin gradually loses its structural and functional characteristics. The skin becomes more fragile and vulnerable to damage, which may contribute to age-related diseases and even death. Skin aging is aggravated by the fact that the skin is in direct contact with extrinsic factors, such as ultraviolet irradiation. While calorie restriction (CR) is the most effective intervention to extend the lifespan of organisms and prevent age-related disorders, its effects on cutaneous aging and disorders are poorly understood. This review discusses the effects of CR and its alternative dietary intake on skin biology, with a focus on skin aging. CR structurally and functionally affects most of the skin and has been reported to rescue both age-related and photo-induced changes. The anti-inflammatory, anti-oxidative, stem cell maintenance, and metabolic activities of CR contribute to its beneficial effects on the skin. To the best of the author’s knowledge, the effects of fasting or a specific nutrient-restricted diet on skin aging have not been evaluated; these strategies offer benefits in wound healing and inflammatory skin diseases. In addition, well-known CR mimetics, including resveratrol, metformin, rapamycin, and peroxisome proliferator-activated receptor agonists, show CR-like prevention against skin aging. An overview of the role of CR in skin biology will provide valuable insights that would eventually lead to improvements in skin health. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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24 pages, 850 KiB

Open AccessReview

Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms

by Dae-Sung Hwangbo, Hye-Yeon Lee, Leen Suleiman Abozaid and Kyung-Jin Min

Nutrients 2020, 12(4), 1194; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12041194 - 24 Apr 2020

Cited by 92 | Viewed by 19206

Abstract

Genetic and pharmacological interventions have successfully extended healthspan and lifespan in animals, but their genetic interventions are not appropriate options for human applications and pharmacological intervention needs more solid clinical evidence. Consequently, dietary manipulations are the only practical and probable strategies to promote health and longevity in humans. Caloric restriction (CR), reduction of calorie intake to a level that does not compromise overall health, has been considered as being one of the most promising dietary interventions to extend lifespan in humans. Although it is straightforward, continuous reduction of calorie or food intake is not easy to practice in real lives of humans. Recently, fasting-related interventions such as intermittent fasting (IF) and time-restricted feeding (TRF) have emerged as alternatives of CR. Here, we review the history of CR and fasting-related strategies in animal models, discuss the molecular mechanisms underlying these interventions, and propose future directions that can fill the missing gaps in the current understanding of these dietary interventions. CR and fasting appear to extend lifespan by both partially overlapping common mechanisms such as the target of rapamycin (TOR) pathway and circadian clock, and distinct independent mechanisms that remain to be discovered. We propose that a systems approach combining global transcriptomic, metabolomic, and proteomic analyses followed by genetic perturbation studies targeting multiple candidate pathways will allow us to better understand how CR and fasting interact with each other to promote longevity. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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25 pages, 977 KiB

Open AccessReview

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

by Dae Hyun Kim, EunJin Bang, Hee Jin Jung, Sang Gyun Noh, Byung Pal Yu, Yeon Ja Choi and Hae Young Chung

Nutrients 2020, 12(2), 422; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020422 - 06 Feb 2020

Cited by 33 | Viewed by 8840

Abstract

Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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18 pages, 2112 KiB

Open AccessReview

Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction

by Toshimitsu Komatsu, Seongjoon Park, Hiroko Hayashi, Ryoichi Mori, Haruyoshi Yamaza and Isao Shimokawa

Nutrients 2019, 11(12), 3068; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11123068 - 16 Dec 2019

Cited by 20 | Viewed by 6271

Abstract

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly depending on nutritional states. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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18 pages, 640 KiB

Open AccessReview

The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention

by Ki Wung Chung and Hae Young Chung

Nutrients 2019, 11(12), 2923; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11122923 - 02 Dec 2019

Cited by 51 | Viewed by 16913

Abstract

Autophagy is an important housekeeping process that maintains a proper cellular homeostasis under normal physiologic and/or pathologic conditions. It is responsible for the disposal and recycling of metabolic macromolecules and damaged organelles through broad lysosomal degradation processes. Under stress conditions, including nutrient deficiency, autophagy is substantially activated to maintain proper cell function and promote cell survival. Altered autophagy processes have been reported in various aging studies, and a dysregulated autophagy is associated with various age-associated diseases. Calorie restriction (CR) is regarded as the gold standard for many aging intervention methods. Although it is clear that CR has diverse effects in counteracting aging process, the exact mechanisms by which it modulates those processes are still controversial. Recent advances in CR research have suggested that the activation of autophagy is linked to the observed beneficial anti-aging effects. Evidence showed that CR induced a robust autophagy response in various metabolic tissues, and that the inhibition of autophagy attenuated the anti-aging effects of CR. The mechanisms by which CR modulates the complex process of autophagy have been investigated in depth. In this review, several major advances related to CR’s anti-aging mechanisms and anti-aging mimetics will be discussed, focusing on the modification of the autophagy response. Full article

(This article belongs to the Special Issue The Effect of Calorie Restriction and Intermittent Fasting on Health and Disease)

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