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Journal ArticleDOI

Effects of Intermittent Fasting on Health, Aging, and Disease

25 Dec 2019-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 381, Iss: 26, pp 2541-2551
TL;DR: Effects of Intermittent Fasting on Health and Aging evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base fasting.
Abstract: Effects of Intermittent Fasting on Health and Aging Evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base...
Citations
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Journal ArticleDOI
TL;DR: Dietary protocols that modify the timing of food intake to deliberately alter the feeding–fasting cycle are discussed to optimise metabolism by timing nutrient intake to the acrophases of metabolic rhythms to improve whole-body insulin sensitivity and glycaemic control, and thereby positively impact metabolic health.
Abstract: The proliferation in the rate of diagnosis of obesity and type 2 diabetes mellitus continues unabated, with current recommendations for primary lifestyle changes (i.e. modification to dietary patterns) having a limited impact in reducing the incidence of these metabolic diseases. Part of the reason for the failure to alter nutritional practices is that current dietary recommendations may be unrealistic for the majority of adults. Indeed, round-the-clock access to energy-dense, nutrient-poor food makes long-term changes to dietary habits challenging. Hence, there is urgent need for innovations in the delivery of evidence-based diet interventions to rescue some of the deleterious effects on circadian biology induced by our modern-day lifestyle. With the growing appreciation that the duration over which food is consumed during a day has profound effects on numerous physiological and metabolic processes, we discuss dietary protocols that modify the timing of food intake to deliberately alter the feeding–fasting cycle. Such chrono-nutrition functions to optimise metabolism by timing nutrient intake to the acrophases of metabolic rhythms to improve whole-body insulin sensitivity and glycaemic control, and thereby positively impact metabolic health.

61 citations


Cites background from "Effects of Intermittent Fasting on ..."

  • ...Several short-term studies report that IF is as effective for weight loss as standard weight-loss diets (see [29]), whereas a 12 month study that compared IF (one day on, one day off), CER and a control diet found that, although the two intervention groups lost weight, insulin sensitivity, blood lipid levels and blood pressure were not improved [42]....

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  • ...Permutations in the pattern of daily food consumption in such dietary regimens are numerous [17, 29, 30] but broadly encompass three approaches: (1) sustained periods of chronic energy restriction (CER), in which daily energy intake is reduced by up to 40%, but meal frequency and timing remain unchanged; (2) intermittent fasting (IF), where one day or several days of fasting are interspersed with normal ad libitum eating patterns, and meal frequency and timing remaining unchanged on the days of food intake; and (3) timerestricted feeding (TRF), in which food is consumed ad libitum throughout a set time period....

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Journal ArticleDOI
TL;DR: This review of previous and recent studies that have advanced the understanding of the transcriptional architecture of the mammalian clock, with a specific focus on epigenetic mechanisms, transcriptomics, and 3D chromatin architecture discusses reciprocal ways in which the clock and metabolism regulate each other to generate metabolic rhythms.
Abstract: All biological processes, living organisms, and ecosystems have evolved with the Sun that confers a 24-hour periodicity to life on Earth. Circadian rhythms arose from evolutionary needs to maximize daily organismal fitness by enabling organisms to mount anticipatory and adaptive responses to recurrent light-dark cycles and associated environmental changes. The clock is a conserved feature in nearly all forms of life, ranging from prokaryotes to virtually every cell of multicellular eukaryotes. The mammalian clock comprises transcription factors interlocked in negative feedback loops, which generate circadian expression of genes that coordinate rhythmic physiology. In this review, we highlight previous and recent studies that have advanced our understanding of the transcriptional architecture of the mammalian clock, with a specific focus on epigenetic mechanisms, transcriptomics, and 3-dimensional chromatin architecture. In addition, we discuss reciprocal ways in which the clock and metabolism regulate each other to generate metabolic rhythms. We also highlight implications of circadian biology in human health, ranging from genetic and environment disruptions of the clock to novel therapeutic opportunities for circadian medicine. Finally, we explore remaining fundamental questions and future challenges to advancing the field forward.

61 citations

Journal ArticleDOI
TL;DR: The authors showed that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice, while maintaining hepatic glucose output and glucose homeostasis.
Abstract: Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.

60 citations

Journal ArticleDOI
TL;DR: In this paper, the authors summarize evidence for the contribution of autophagy to health and lifespan and provide examples of the bidirectional interplay between autophagic pathways and several of the so-called hallmarks of aging.

59 citations

Journal ArticleDOI
TL;DR: The role of the microbiome in the development and pathogenesis of hypertension is explored in this paper, where the authors provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure.
Abstract: The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension

59 citations

References
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Journal ArticleDOI
10 Jul 2009-Science
TL;DR: Findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research demonstrate that CR slows aging in a primate species.
Abstract: Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals Furthermore, CR delayed the onset of age-associated pathologies Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy These data demonstrate that CR slows aging in a primate species

2,114 citations

Journal ArticleDOI
TL;DR: The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology of dementia, but which of these mechanisms are clinically relevant is unclear.
Abstract: The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.

1,836 citations

Journal ArticleDOI
TL;DR: Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination.

1,442 citations

Journal ArticleDOI
TL;DR: In this article, it was shown that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs, but this can be nullified by amino acid or protein supplementation.
Abstract: Starvation entails a progressive selection of fat as body fuel. Soon after a meal glucose utilisation by muscle ceases and fatty acids are used instead. Ketoacid levels in blood become elevated over the first week, and the brain preferentially uses these instead of glucose. The net effect is to spare protein even further, as glucose utilisation by brain is diminished. Nevertheless, there is still net negative nitrogen balance, but this can be nullified by amino acid or protein supplementation. Insulin appears to be the principal regulatory hormone. Recent data suggest that decreased levels of active T3 may play a role by sparing otherwise obligated calories by decreasing metabolic needs.

1,293 citations


"Effects of Intermittent Fasting on ..." refers background in this paper

  • ...In the fed state, blood levels of ketone bodies are low, and in humans, they rise within 8 to 12 hours after the onset of fasting, reaching levels as high as 2 to 5 mM by 24 hours.(14,15) In rodents, an elevation of plasma ketone levels occurs within 4 to 8 hours after the onset of fasting, reaching millimolar levels within 24 hours....

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Journal ArticleDOI
TL;DR: The results point to a central role for the PGC-1 family in integrating mitochondrial biogenesis and energy production with many diverse cellular functions.

990 citations

Trending Questions (3)
Does the timeframe of intermitend fasting have an influence on the effect?

The paper does not provide information about the specific timeframe of intermittent fasting and its influence on the effects.

What are the pros and cons of periodic fasting while on a carnivore diet?

The provided paper does not mention the pros and cons of periodic fasting while on a carnivore diet. The paper discusses the effects of intermittent fasting on health, aging, and disease.

How does intermittent fasting impact aging?

Intermittent fasting can trigger a metabolic switch that may impact aging.