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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...
Topics: Intermittent fasting (79%)
Citations
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Journal ArticleDOI
Sofia Cienfuegos1, Kelsey Gabel1, Faiza Kalam1, Mark Ezpeleta1  +5 moreInstitutions (1)
01 Sep 2020-Cell Metabolism
TL;DR: It is suggested that 4- and 6-h TRF induce mild reductions in body weight over 8 weeks and show promise as interventions for weight loss and may also improve some aspects of cardiometabolic health.
Abstract: Summary Time-restricted feeding (TRF) regimens have grown in popularity; however, very few studies have examined their weight-loss efficacy. We conducted the first human trial (Clinicaltrials.gov NCT03867773) to compare the effects of two popular forms of TRF (4 and 6 h) on body weight and cardiometabolic risk factors. Adults with obesity were randomized to 4-h TRF (eating only between 3 and 7 p.m.), 6-h TRF (eating only between 1 and 7 p.m.), or a control group (no meal timing restrictions). After 8 weeks, 4- and 6-h TRF produced comparable reductions in body weight (∼3%), insulin resistance, and oxidative stress, versus controls. Energy intake was reduced by ∼550 kcal/day in both TRF groups, without calorie counting. These findings suggest that 4- and 6-h TRF induce mild reductions in body weight over 8 weeks and show promise as interventions for weight loss. These diets may also improve some aspects of cardiometabolic health.

74 citations


Journal ArticleDOI
31 Mar 2020-
TL;DR: A review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age.
Abstract: The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, geros "old man" and epilavis, "harmful") infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.

47 citations


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

  • ...5mM and continue to increase within the first 48 hours to 1 to 2mM [108]....

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Journal ArticleDOI
Philipp Kasper1, Anna Martin1, Sonja Lang2, Fabian Kütting1  +3 moreInstitutions (3)
TL;DR: The underlying pathophysiological mechanisms linking NAFLD and CVD are described, the role ofNAFLD as a metabolic dysfunction associated cardiovascular risk factor is discussed, and common cardiovascular manifestations in NAFLd patients are focused on.
Abstract: Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.

43 citations


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

  • ...Intermittent fasting with energy restriction for about 10-16 h is promising approach in this context, as it has been shown to mediate robust disease modifying effects on chronic metabolic disorders such as obesity, T2DM and CVD [156]....

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  • ...Intermittent fasting with energy restriction for about 10-16 h is promising approach in this context, as it has been shown to mediate robust disease modifying effects on chronic metabolic disorders such as obesity, T2DM and CVD [156]....

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  • ...In the liver, prolonged energy restriction results in a depletion of glycogen storage that subsequently triggers a metabolic switch towards the use of fatty acids and ketone bodies as energy sources [156]....

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  • ...While growing evidence indicates that intermittent fasting is associated with numerous cardiovascular benefits, including reduced blood pressure, lipid levels, and reduced inflammatory marker, data on the effects of intermittent fasting in large cohorts of NAFLD patients are sparse [155, 156]....

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Journal ArticleDOI
Mikiko Watanabe1, Rossella Tozzi1, Renata Risi1, Dario Tuccinardi2  +5 moreInstitutions (2)
24 Mar 2020-Obesity Reviews
TL;DR: Clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions involved in the ketogenic diet and nonalcoholic fatty liver disease are focused on, to provide an accurate revision of current literature on KDs and NAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.

40 citations


Journal ArticleDOI
Ping Song1, Junqing An1, Ming-Hui Zou1Institutions (1)
10 Mar 2020-Cells
TL;DR: Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.
Abstract: Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, and apoptotic resistance in multiple organs due to various stressors. Excessive accumulation of senescent cells in numerous tissues leads to multiple chronic diseases, tissue dysfunction, age-related diseases and organ ageing. Immune cells can remove senescent cells. Immunaging or impaired innate and adaptive immune responses by senescent cells result in persistent accumulation of various senescent cells. Although senolytics—drugs that selectively remove senescent cells by inducing their apoptosis—are recent hot topics and are making significant research progress, senescence immunotherapies using immune cell-mediated clearance of senescent cells are emerging and promising strategies to fight ageing and multiple chronic diseases. This short review provides an overview of the research progress to date concerning senescent cell-caused chronic diseases and tissue ageing, as well as the regulation of senescence by small-molecule drugs in clinical trials and different roles and regulation of immune cells in the elimination of senescent cells. Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.

40 citations


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

  • ...In addition, β-hydroxybutyrate (β-HB) may mediate the effect of a ketogenic diet [113,114], intermittent fasting [115] or exercise [116] on healthspan extension or neuroregeneration because of its anti-inflammation [117], inhibition of vascular cell senescence [118] or immune activation by the formation and maintenance of CD8+ memory T cells [119]....

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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

1,934 citations


Journal ArticleDOI
01 Jan 2006-Lancet Neurology
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.

1,633 citations


Journal ArticleDOI
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.

1,232 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
06 Jun 2012-Cell Metabolism
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.
Abstract: While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. 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. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

1,104 citations


Journal ArticleDOI
13 Sep 2012-Nature
TL;DR: A separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate is suggested.
Abstract: Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

893 citations


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

  • ...One of the studies, at the University of Wisconsin, showed a positive effect of caloric restriction on both health and survival,(31) whereas the other study, at the National Institute on Aging, showed no significant reduction in mortality, despite clear improvements in overall health.(32) Differences in the daily caloric intake, onset of the intervention, diet composition, feeding protocols, sex, and genetic background may explain the differential effects of caloric restriction on life span in the two studies....

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