Age‐Related Changes in Postprandial Plasma Glucose, Insulin, and Free Fatty Acid Concentrations in Nondiabetic Individuals

Fraze, E.; Chiou, Y-A. Melody; Chen, Y-D. Ida; Reaven, Gerald M.

doi:10.1111/j.1532-5415.1987.tb02313.x

Cited by 66 publications

(29 citation statements)

References 16 publications

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“…Aging is associated with alterations in body fat distribution, obesity and insulin resistance [113,114]. High levels of leptin are observed with obesity in humans and rodents [115,116].…”

Section: The Role Of Adipose Tissue In Aging Retardation By Dietary Rmentioning

confidence: 99%

Metabolic Reprogramming in Dietary Restriction

Anderson

Weindruch²

2006

Interdisciplinary Topics in Gerontology

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It is widely accepted that energy intake restriction without essential nutrient deficiency delays the onset of aging and extends life span. The mechanism underlying this phenomenon is still unknown though a number of different, nonmutually exclusive explanations have been proposed. In each of these, different facets of physiology play the more significant role in the mechanism of aging retardation. Some examples include the altered lipid composition model, the immune response model and models describing changes in endocrine function. In this paper we propose the hypothesis that metabolic reprogramming is the key event in the mechanism of dietary restriction, and the physiological effects at the cellular, tissue and organismal level may be understood in terms of this initial event.Dietary restriction (DR) is the most successful intervention tested to date in mammals which greatly extends maximum life span and keeps animals 'younger longer' [1][2][3]. Consequently, any hypothesis about the etiology of aging must reconcile the effects of DR on aging. With increased knowledge of the mechanism of DR, we stand to gain a considerable insight into the process of aging.We propose that a change in the regulation of energy metabolism in response to DR is the primary step in the retardation of aging ( fig. 1). First we describe the evidence in support of metabolic reprogramming, a switch to an altered metabolic state, by DR in mice. Next we consider evidence for metabolic shifts in other model organisms where life span is extended by DR or by genetic manipulation. Then we focus on changes in mitochondrial energy metabolism with age and DR in mammals. Next we will explore the effects of altered mitochondrial function in the context of reactive oxygen species (ROS) generation and oxidative stress. Finally we describe the metabolic and morphological changes in white adipose tissue that we believe are a result of altered mitochondrial function. We propose that the activation of adipose tissue through metabolic reprogramming is critical to the mechanism of DR and that it leads to the changes in the animal physiology that are described in the models indicated above. Metabolic Reprogramming in Tissues from Dietary-Restricted AnimalsThe inverse linear relationship between calorie intake and life span in mice [4] suggests that genes central to energy metabolism may be critical in the underlying mechanism of DR in

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“…Aging is associated with alterations in body fat distribution, obesity and insulin resistance [113,114]. High levels of leptin are observed with obesity in humans and rodents [115,116].…”

Section: The Role Of Adipose Tissue In Aging Retardation By Dietary Rmentioning

confidence: 99%

Metabolic Reprogramming in Dietary Restriction

Anderson

Weindruch²

2006

Interdisciplinary Topics in Gerontology

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“…Aging is known to be associated with obesity phenotype, alterations in body fat distribution and the development of insulin and leptin resistance (Enzi et al, 1986;Fraze et al, 1987;Wang et al, 2001;Ma et al, 2002). Several reports have suggested that reduction in white adipose tissue (WAT) may be a primary factor in the longevity induced by CR.…”

Section: Introductionmentioning

confidence: 99%

Modulation of white adipose tissue proteome by aging and calorie restriction

et al. 2010

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SummaryAging is associated with an accrual of body fat, progressive development of insulin resistance and other obesity comorbidities that contribute to decrease life span. Caloric restriction (CR), which primarily affects energy stores in adipose tissue, is known to extend life span and retard the aging process in animal models. In this study, a proteomic approach combining 2-DE and MS was used to identify proteins modulated by aging and CR in rat white adipose tissue proteome. Proteomic analysis revealed 133 differentially expressed spots, 57 of which were unambiguously identified by MS. Although CR opposed part of the age-associated protein expression patterns, many effects of CR were on proteins unaltered by age, suggesting that the effects of CR on adipose tissue are only weakly related to those of aging. Particularly, CR and aging altered glucose, intermediate and lipid metabolism, with CR enhancing the expression of enzymes involved in oxalacetate and NADPH production, lipid biosynthesis and lipolysis. Consistently, insulin-b and b3-adrenergic receptors were also increased by CR, which denotes improved sensitivity to lipogenic ⁄ lipolytic stimuli. Other beneficial outcomes of CR were an improvement in oxidative stress, preventing the age-associated decrease in several antioxidant enzymes. Proteins involved in cytoskeleton, iron storage, energy metabolism and several proteins with novel or unknown functions in adipose tissue were also modulated by age and ⁄ or CR. Such orchestrated changes in expression of multiple proteins provide insights into the mechanism underlying CR effects, ultimately allowing the discovery of new markers of aging and targets for the development of CR-mimetics.

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“…The rate of glycolysis was estimated from the rate of conversion of [ 3 H-3]glucose to 3 H 2 O as previously described (12,13). Because tritium on the C-3 position of glucose is lost to water during glycolysis, it can be assumed that plasma tritium is present either in 3 H water or in glucose. Plasma-tritiated water specific activity was determined by liquid scintillation counting of the protein-free supernatant (Somogyi filtrate) before and after evaporation to dryness.…”

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confidence: 99%

Leptin Resistance During Aging Is Independent of Fat Mass

et al. 2002

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Increased fat mass, abdominal adiposity, and insulin resistance are typical findings in aging mammals and are frequently associated with leptin resistance and increased plasma leptin levels. To examine whether leptin's failure in aging is due to aging per se or to changes in body fat mass or distribution, we studied aging rats that underwent calorie restriction throughout their lives, maintaining their youthful body fat pattern and metabolic profile. Leptin's action was assessed by measuring its ability to regulate food intake, fat mass and its distribution, peripheral and hepatic insulin action, and its own gene expression in fat. Our results show that leptin's action is markedly diminished in aging rats, independently of their body fat pattern. Leptin's failure in this model suggests its causative role in the metabolic decline seen with aging. Diabetes 51: 1016 -1021, 2002 A ging is associated with a metabolic decline characterized by the development of changes in fat distribution, obesity, and insulin resistance (1-3). All these metabolic alterations are associated with a variety of age-related diseases that subsequently result in increased mortality (4 -9). It has been recently demonstrated that leptin, a 16-kDa fat-derived peptide, can modulate many of the metabolic alterations characteristic of aging (10 -12). Chronic administration of leptin decreases food intake and induces reduction in fat mass (FM) and visceral fat (VF), with a parallel significant improvement in hepatic and peripheral insulin action (10 -14). This finding suggests that alterations in leptin action may play a role in the metabolic phenotype of aging. Indeed, the dramatic increase in plasma leptin levels in aging animal models and in humans suggests a leptinresistant state (15-18). Although the increase in plasma leptin concentration in aging may be partially attributed to the development of obesity (which is associated with leptin resistance [19]), the increase in plasma leptin level during aging is often disproportionate to the increase in the amount of fat (16 -19). We therefore hypothesize that aging per se is associated with a failure in leptin's action, independent of obesity or changes in body fat distribution. Thus, leptin resistance of aging may represent a perpetuating factor in developing and maintaining obesity and its clinical consequences.Because aging is frequently associated with obesity, it is difficult to identify whether leptin failure is due to obesity, the process of aging per se, or both. To overcome this difficulty, we used caloric restriction throughout aging in a rodent model and prevented the typical age-related changes in body composition. We reasoned that aging rats would remain leptin resistant even when kept relatively lean and "metabolically young" by calorie restriction. RESEARCH DESIGN AND METHODS Animals.A total of 36 male Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA) were housed in individual cages and subjected to a standard light (6:00 A.M. to 6:00 P.M) to dark (6:00 P.M. to 6:0...

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Age‐Related Changes in Postprandial Plasma Glucose, Insulin, and Free Fatty Acid Concentrations in Nondiabetic Individuals

Cited by 66 publications

References 16 publications

Metabolic Reprogramming in Dietary Restriction

Metabolic Reprogramming in Dietary Restriction

Modulation of white adipose tissue proteome by aging and calorie restriction

Leptin Resistance During Aging Is Independent of Fat Mass

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