Calorie restriction in humans: An update.
TL;DR: The effects of CR in non-obese humans on physiological parameters of energy metabolism and metabolic risk factors of age-associated disease in great detail are discussed.
About: This article is published in Ageing Research Reviews.The article was published on 2017-10-01 and is currently open access. It has received 341 citations till now. The article focuses on the topics: Calorie restriction & CALERIE.
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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...
730 citations
TL;DR: The purpose of the article is to highlight the recent progress on the mitochondrial role in metabolic syndromes and also summarize the progress of mitochondria-targeted molecules as therapeutic targets to treat metabolic Syndromes.
724 citations
Cites background from "Calorie restriction in humans: An u..."
...Finally, data from various epidemiological, clinical and experimental studies have shown that CR exerts additional beneficial health effects by inhibiting key nutrient-sensing and inflammatory pathways and remains the cornerstone in the prevention and treatment of metabolic disorders [190]....
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TL;DR: Interventions, including changes to lifestyle and medical innovations, are needed to prevent disease and increase late-life health in humans.
Abstract: Longer human lives have led to a global burden of late-life disease However, some older people experience little ill health, a trait that should be extended to the general population Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies
630 citations
TL;DR: Accumulating evidence indicates that the five most important adaptations induced by the Mediterranean dietary pattern are: lipid-lowering effect, protection against oxidative stress, inflammation and platelet aggregation, modification of hormones and growth factors involved in the pathogenesis of cancer, inhibition of nutrient sensing pathways by specific amino acid restriction, and gut microbiota-mediated production of metabolites influencing metabolic health.
Abstract: Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy. Data from several randomized clinic trials have demonstrated a beneficial effect in the primary and secondary prevention of cardiovascular disease, type 2 diabetes, atrial fibrillation, and breast cancer. The exact mechanism by which an increased adherence to the traditional Mediterranean diet exerts its favorable effects is not known. However, accumulating evidence indicates that the five most important adaptations induced by the Mediterranean dietary pattern are: (a) lipid-lowering effect, (b) protection against oxidative stress, inflammation and platelet aggregation, (c) modification of hormones and growth factors involved in the pathogenesis of cancer, (d) inhibition of nutrient sensing pathways by specific amino acid restriction, and (e) gut microbiota-mediated production of metabolites influencing metabolic health. More studies are needed to understand how single modifications of nutrients typical of the Mediterranean diet interact with energy intake, energy expenditure, and the microbiome in modulating the key mechanisms that promote cellular, tissue, and organ health during aging.
371 citations
Cites background from "Calorie restriction in humans: An u..."
...Calorie restriction without malnutrition has been shown to be extremely effective in cancer prevention in rodents and monkeys, and in humans results in major reductions of several metabolic and hormonal factors implicated in the pathogenesis of numerous common cancers and in the biology of aging itself (65)....
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TL;DR: The breadth and depth of metabolic flexibility and its impact on health and disease are discussed and important advances in metabolic flexibility research are outlined and medical horizons and translational aspects are outlined.
Abstract: The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.
307 citations
References
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TL;DR: Finding that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type raises the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation.
Abstract: We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.
3,146 citations
"Calorie restriction in humans: An u..." refers background in this paper
...regulates the HSF/HSP pathway and down-regulates the activity of the insulin/IGF pathway, which have been shown to play a key roles in promoting health and longevity in several experimental model organisms (Hsu et al., 2003; Kenyon et al., 1993; Yokoyama et al., 2002)....
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...…that long-term CR in humans upregulates the HSF/HSP pathway and down-regulates the activity of the insulin/IGF pathway, which have been shown to play a key roles in promoting health and longevity in several experimental model organisms (Hsu et al., 2003; Kenyon et al., 1993; Yokoyama et al., 2002)....
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TL;DR: Dietary restriction and reduced activity of nutrient-sensing pathways may slow aging by similar mechanisms, which have been conserved during evolution, and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
Abstract: When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
2,522 citations
"Calorie restriction in humans: An u..." refers methods in this paper
...Serum TNFα, IL6, fasting glucose and insulin were also remarkably low, and insulin sensitivity based on HOMA-IR and the Matsuda and DeFronzo indexes were improved (Fontana et al., 2010)....
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TL;DR: These findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot and Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
Abstract: Background— Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results— Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, ...
2,501 citations
"Calorie restriction in humans: An u..." refers background in this paper
...T2DM and insulin resistance are related to increased adipocyte size and ectopic fat deposition including the liver and skeletal muscle (Fox et al., 2007; Perry et al., 2014; Weyer et al., 2000)....
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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
"Calorie restriction in humans: An u..." refers background in this paper
...Moreover, in the Wisconsin National Primate Research Center (WNPRC) study, CR has been shown to slow down age-related sarcopenia, hearing loss and brain atrophy in several subcortical regions (Colman et al., 2009; Colman et al., 2014)....
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...(ref#) in this issue, accumulating data from two long-term ongoing primate studies clearly indicate that 30% CR drastically reduces the incidence of glucose intolerance/type 2 diabetes, cardiovascular disease and cancer (Colman et al., 2009; Colman et al., 2014; Mattison et al., 2012)....
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...#) in this issue, accumulating data from two long-term ongoing primate studies clearly indicate that 30% CR drastically reduces the incidence of glucose intolerance/type 2 diabetes, cardiovascular disease and cancer (Colman et al., 2009; Colman et al., 2014; Mattison et al., 2012)....
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