scholarly journals Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner

GeroScience ◽  
2021 ◽  
Author(s):  
Yoko O. Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Rebecca Schugar ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Dietary Intervention ◽  
Caloric Intake ◽  
Production Capacity ◽  
Late Life ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Sexually Dimorphic ◽  
Average Life Expectancy ◽  
Multiple Components

AbstractGlobal average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.

scholarly journals Intermittent Fasting: From Calories to Time Restriction

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 116-116
Author(s):  
Rafael de Cabo
Keyword(s):  
Caloric Intake ◽  
Model Organisms ◽  
Current Status ◽  
Laboratory Animals ◽  
Intermittent Fasting ◽  
Eating Patterns ◽  
Daily Energy Intake ◽  
Daily Energy ◽  
Time Restriction ◽  
Daily Time

Abstract Classic implementation of calorie restriction (CR) in laboratory animals increases health and longevity in most model organisms. Traditionally, chronic CR is the reduction of daily energy intake without malnutrition. Recently, paradigms have emerged that recapitulate some of the beneficial aspects of this intervention, avoiding some of its challenges. The length of daily fasting length and periodicity have emerged as potential drivers behind CR’s beneficial health effects. Numerous strategies and eating patterns, including prolonged periods of fasting, have been successfully developed to mimic many of CR’s benefits without its austerity. These new feeding protocols range from short mealtimes designed to interact with our circadian system (daily time-restricted feeding) to more extended fasting regimens known as intermittent fasting. We will discuss the current status of knowledge on different strategies to reap the benefits of CR on metabolic health in rodent models and humans without the rigor of chronic reductions in caloric intake.

scholarly journals Late-Onset Intermittent Fasting Decreases Aging-Related Frailty

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 125-125
Author(s):  
Yoko Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Christopher Hine
Keyword(s):  
Therapeutic Potential ◽  
Late Onset ◽  
Frailty Index ◽  
Late Life ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Chow Diet ◽  
Positive Effects ◽  
Ad Libitum ◽  
H2s Production

Abstract Global average life expectancy continues to rise. As aging increases likelihoods of exhibiting geriatric syndromes (a.k.a. frailty), there is a need for effective anti-aging treatments. Multiple studies have shown the positive effects of dietary restriction (DR) on lifespan in various model organisms. However, DR is not widely implemented in older adults due to issues with patient compliance and the overall lack of understanding on the effects of DR initiated later in life. Thus, the present study tested whether late-life DR, specifically Every-Other-Day (EOD) fasting, attenuates aging-related frailty using a modified and simplified frailty index in mice. Briefly, 20-month old male and female C57BL/6 mice (human equivalent of 65 years) that had been on a control chow diet ad libitum during adulthood were placed on EOD fasting or ad libitum feeding for 2.5 months. Their frailty index was identified using an indirect calorimeter, glucose tolerance test, novel object place recognition test, forelimb grip strength meter, and rotarod. We found that late-life EOD fasting decreased overall caloric intake in males but not in females. In addition, EOD fasting significantly improved metabolic, musculoskeletal, and cognitive endpoints in male mice, but enhanced only some of these in female mice. Furthermore, EOD fasting improved hydrogen sulfide (H2S) production capacity and its associated sulfhydration signaling in tissues, which positively correlated with improvements in frailty measures. We conclude that EOD fasting implemented late in life can have therapeutic potential in the clinic. We are currently investigating the necessity of H2S production for DR mediated benefits and longevity.

scholarly journals DDRE-31. FEASIBILITY AND BIOLOGIC ACTIVITY OF A KETOGENIC / INTERMITTENT FASTING DIET IN GLIOMA PATIENTS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Karisa Schreck ◽  
Fang-Chi Hsu ◽  
Adam Berrington ◽  
Bobbie Henry-Barron ◽  
Diane Vizthum ◽  
...  
Keyword(s):  
Body Mass ◽  
Mr Spectroscopy ◽  
Hemoglobin A1c ◽  
Dietary Intervention ◽  
Intermittent Fasting ◽  
Who Grade ◽  
Cerebral Activity ◽  
Food Records ◽  
Systemic Activity ◽  
Patient Reported

Abstract BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories<20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

scholarly journals The Effects of Intermittent Fasting on Brain and Cognitive Function

2021 ◽  
Author(s):  
Jip Gudden ◽  
Alejandro Arias Vasquez ◽  
Mirjam Bloemendaal
Keyword(s):  
Cognitive Function ◽  
Animal Studies ◽  
Randomized Clinical Trials ◽  
Caloric Intake ◽  
Autism Spectrum ◽  
Future Research ◽  
Intermittent Fasting ◽  
Long Term Effects ◽  
Functional Changes ◽  
Positive Effects

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 hours, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which - through metabolic, cellular and circadian mechanisms - lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischaemic stroke, autism spectrum disorder and mood- and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Also, variations in fasting patterns, total caloric intake and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and Randomized Clinical Trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

The effects of Ramadan intermittent fasting on the underlying mechanisms of force production capacity during maximal isometric voluntary contraction

2019 ◽  
Vol 36 (5) ◽  
pp. 698-708 ◽  
Author(s):  
Helmy Gueldich ◽  
Firas Zghal ◽  
Rihab Borji ◽  
Hamdi Chtourou ◽  
Sonia Sahli ◽  
...  
Keyword(s):  
Production Capacity ◽  
Force Production ◽  
Voluntary Contraction ◽  
Intermittent Fasting ◽  
Underlying Mechanisms

scholarly journals Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice

2021 ◽  
Author(s):  
Guozhu Zhang ◽  
Andrew Deighan ◽  
Anil Raj ◽  
Laura Robinson ◽  
Hannah J. Donato ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Dietary Intervention ◽  
Early Adulthood ◽  
Genetic Correlations ◽  
Intermittent Fasting ◽  
Cardiac Physiology ◽  
Dietary Interventions ◽  
Diversity Outbred ◽  
Outbred Mice ◽  
One Year

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of early adulthood population. In this article, we investigated the effect of six month exposure of either caloric restriction or intermittent fasting on a broad range of physiological traits in 960 one year old Diversity Outbred mice. We found caloric restriction and intermittent fasting affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilties ranged from 0.04-0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of early adult-hood mice following six months of dietary intervention.

scholarly journals Circadian Rhythms and Obesity in Mammals

ISRN Obesity ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Oren Froy
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Energy Homeostasis ◽  
Caloric Intake ◽  
Public Health Problem ◽  
Transport Systems ◽  
Intermittent Fasting ◽  
New Approach ◽  
Circadian Expression ◽  
Activity Of Enzymes

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.

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