Fasting or caloric restriction for Healthy Aging

doi:10.1016/j.exger.2013.04.011

Experimental Gerontology

Volume 48, Issue 10, October 2013, Pages 1003-1005

https://doi.org/10.1016/j.exger.2013.04.011 Get rights and content

Abstract

Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed.

Section snippets

Future directions

A key issue for future research examining the effects of caloric restriction in humans is whether or not the promising findings from initial human trials translate to non-overweight individuals whose body mass index (BMI; kg/m²) falls in the healthy range (i.e., BMI Range = 20.0 – 24.9 kg/m²). This possibility is currently being explored by the CALERIE Phase 2 study (Rochon et al., 2011). Specifically, the CALERIE Phase 2 study is examining the long-term effects of a 25% reduction of ad libitum

Conflict of interest

The authors have no conflicts of interests.

Acknowledgments

Support was provided by the University of Florida Claude D. Pepper Older Americans Independence Center (NIH/NIA P30AG028740) and the Clinical and Translational Science Institute (NIH/NCRR UL1TR000064). Stephen Anton is supported by a K23 AT004251-01A2, an Early Career Investigator Award from the American Heart Association (09CRP2390173), and Thomas H. Maren Foundation.

References (52)

J.P. Aris et al.
Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast
Exp. Gerontol.
(2013)
N.M. Avena et al.
Comparing the effects of food restriction and overeating on brain reward systems
Exp. Gerontol.
(2013)
A.J. Carlson et al.
Apparent prolongation of the life span of rats by intermittent fasting
J. Nutr.
(1946)
E.A. Dannecker et al.
The effect of fasting on indicators of muscle damage
Exp. Gerontol.
(2013)
S. Devaraj et al.
High-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome
Metabolism
(2008)
C. Han et al.
Maintaining good hearing: Calorie restriction, Sirt3, and glutathione
Am. J. Clin. Nutr.
(2013)
L.K. Heilbronn et al.
Calorie restriction and aging: review of the literature and implications for studies in humans
Am. J. Clin. Nutr.
(2003)
T. Hofer et al.
Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction
Mech. Ageing Dev.
(2009)
R.G. Katare et al.
Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway
J. Mol. Cell. Cardiol.
(2009)
Y.Y. Lam et al.
Resveratrol vs. calorie restriction: Data from rodents to humans
Exp. Gerontol.
(2013)

L. Fontana et al.

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

Proc. Natl. Acad. Sci. U. S. A.

(2004)

Cited by (84)

Adaptive metabolic response to short-term intensive fasting
2024, Clinical Nutrition
Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney.
The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study.
Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF.
The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.
Therapeutic fasting
2023, Ketogenic: The Science of Therapeutic Carbohydrate Restriction in Human Health
Fasting is a voluntary, controlled period of abstinence from food that is important to human evolution and has medical, spiritual, and cultural significance in most areas of the world. However, in Westernised countries, incidence and duration of fasting has decreased due to dietary emphasis on snacking. This shift has profound health effects due to the continual suppression of fasting-state gluconeogenesis, nutritional ketosis, and protein conservation, often resetting the cycle before blood glucose and insulin falls. Patients may voice concerns over malnutrition or nutrient depletion, though evidence underscores the physiological differences between fasting (benefits) and starvation (complications). Contraindications and cautions are few but require consideration. Fasting is an effective regimen as it minimises time and financial expenditure, in addition to having health benefits and enhancing longevity.
Nutrition and upper gastrointestinal cancers: An overview of current understandings
2022, Seminars in Cancer Biology
Upper gastrointestinal (UGI) cancers are among the most common cancers in the world, four of them being among the top eight causes of cancer related mortality. Included among UGI cancers are oesophageal, gastric, liver, biliary, pancreatic and small intestinal cancers. Despite more than half a century of well designed epidemiological (large cohort and case-control studies) and a limited number of experimental studies into the role of nutrition on UGI cancer, there is much inconsistency in the findings. Studies have reported significant associations of various food types and UGI cancers, but there are issues with reproducibility. Over the years, numerous meta-analyses have been conducted in an attempt to harmonize available data. On the whole, it is well accepted that fruit and vegetables reduce UGI cancer risk, while processed foods increase the risk. The role of antioxidants in protecting against UGI carcinogenesis is of great interest, but controversial. There is evidence that specific diets, such the Mediterranean or Okinawa, are associated with reduced cancer risk at a population level, but it is less clear if adopting them reduces risk in otherwise high-risk locations. In this review, I will discuss some of the available literature from selected original publications, systematic reviews and meta-analyses on the influence of diet on UGI cancers. I will also provide a brief overview of future directions that have the potential to provide specific evidence on how diet could be modified to reduce the growing global burden of UGI cancers.
Use of Minimally Invasive Methods to Assess Fuel Utilization and Circadian Rhythms in Older Adults
2024, Journal of Visualized Experiments
Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research
2023, Nutrition and Metabolism
Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
2023, PLoS ONE

View all citing articles on Scopus

View full text

Fasting or caloric restriction for Healthy Aging

Abstract

Section snippets

Future directions

Conflict of interest

Acknowledgments

Exp. Gerontol.

Exp. Gerontol.

J. Nutr.

Exp. Gerontol.

Metabolism

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Mech. Ageing Dev.

J. Mol. Cell. Cardiol.

Exp. Gerontol.

Atherosclerosis

Mech. Ageing Dev.

Exp. Gerontol.

Exp. Gerontol.

Exp. Gerontol.

J. Nutr.

Exp. Gerontol.

Short- and long-term effects of continuous versus intermittent restrictive diet approaches on body composition and the metabolic profile in overweight and obese postmenopausal women: a pilot study

Menopause

Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction

Exp. Gerontol.

Acute hyperglycaemia: a ‘new’ risk factor during myocardial infarction

Eur. Heart J.

Postprandial hyperglycemia and diabetes complications: is it time to treat?

Diabetes

Recent advances in calorie restriction research on aging

Exp. Gerontol.

Calorie restriction increases muscle mitochondrial biogenesis in healthy humans

PLoS Med.

Caloric restriction delays disease onset and mortality in rhesus monkeys

Science

Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities

Circ. Res.

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

Proc. Natl. Acad. Sci. U. S. A.