- Can short-term dietary restriction and fasting have a long-term anticarcinogenic effect?
These results suggest that the immediate anticarcinogenic action of DR is to slow down the expansion of initiated clones, but that several months of DR may be sufficient for the elimination of a significant portion of initiated precancerous clones through apoptosis.
- Anti-inflammatory mechanisms of dietary restriction in slowing aging processes
DR attenuates the age-related activation of astrocytes and microglia with concomitant beneficial effects on neurodegeneration and cognition. Increasing evidence suggests that common pathways are emerging that link many normal aging inflammatory processes with age-related diseases such as Alzheimer, cancer, diabetes and cardiovascular disease.
- Metabolic reprogramming in dietary restriction
It is widely accepted that energy intake restriction without essential nutrient deficiency delays the onset of aging and extends life span.
- Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle
These data indicate that CR begun in late middle age can retard age-associated fiber loss and fiber type changes, as well as increases in the number of skeletal muscle fibers showing mitochondrial enzyme abnormalities. CR also decreased the accumulation of mtDNA deletions.
- Influence of the restriction of individual dietary components on longevity and age-related disease of Fischer rats: the fat component and the mineral component
The influence of restricting either the fat or the mineral component of the diet to the same extent as they are restricted in the life-prolonging, food-restriction paradigm but without restricting calories was studied in regard to longevity and age-related pathologic lesions of barrier-maintained male Fischer 344 rats. Neither the restriction of fat nor the restriction of mineral influenced the median length of life or maximum life span as indicated by the age of the 10th percentile survivors. Restricting the dietary fat did retard the development of chronic nephropathy and associated lesions, but it also increased the prevalence of lymphoma and leukemia. The development of chronic nephropathy was not significantly affected by restricting the mineral component of the diet.
- Effect of age and diet on insulin secretion and insulin action in the rat
These results suggest that aging leads to marked changes in both insulin secretion and insulin action. The decline in glucose-stimulated insulin secretion per unit endocrine pancreas appears to be an inevitable consequence of the aging process. In contrast, the age-related changes in islet size, insulin response to a glucose load, and in vivo insulin-stimulated glucose uptake are extremely responsive to variations in amount and kind of calories.
- Impact of a moderately energy-restricted diet on energy metabolism and body composition in non-obese men
Under conditions of a controlled moderately energy-restricted diet in daily life a significant weight loss can be induced, similar to that observed after a balanced dietary deficit, providing 5 MJ/day. In addition, moderate energy restriction induces a decrease in fat-free mass and a fall in RMR.
- Caloric restriction and aging
The relationship between eating less and greater longevity is explored. The author notes that eating less, but ensuring an adequate supply of protein, fat, vitamins, and minerals, has been shown to improve the health and longevity of rodents. The relevance of these findings to humans is considered.
- Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence
Lifelong dietary restriction beginning at 3 to 6 weeks of age in rodents is known to decelerate the rate of aging, increase mean and maximum life-spans, and inhibit the occurrence of many spontaneous cancers. Little is known about the effects of dietary restriction started in middle age. In the experiments now reported the food intake of 12- to 13-month-old mice of two long-lived strains was restricted by using nutrient-enriched diets in accordance with the concept of "undernutrition without malnutrition." The mice on the restricted diet averaged 10 to 20 percent increases in mean and maximum survival times compared to the control mice. Spontaneous lymphoma was inhibited by the food restriction.
- Caloric restriction and immunosenescence: a current perspective
The age-related decrease in immunologic function is believed to be the major predisposing factor contributing to increased morbidity and mortality with age. Hence, the restoration of immunologic function is expected to have a beneficial effect in reducing pathology and maintaining a healthy condition in advanced age. Among various intervention strategies, caloric restriction (CR) has been shown to be the most powerful modulator of aging process. It is the most efficacious means of increasing longevity and reducing pathology. Several mechanisms have been proposed to explain its beneficial and robust action on various physiological systems, including the immune system. Experimental evidence suggests that CR increases longevity and reduces pathology through its action on the immune system. The observation that CR attenuates immunosenescence has provided a rationale for studying whether CR exerts its action through modulation of gene expression. The available data indicate that the effect of CR on signal transduction and gene expression can vary considerably from gene to gene and from one signaling molecule to another. This review summarizes the studies on the influence of CR on aging immune system and discusses the current state of knowledge on the molecular mechanisms responsible for the immunomodulatory action of caloric restriction.
- Dietary Restriction Initiated in Late Adulthood Can Reverse Age-related Alterations of Protein and Protein Metabolism
Taking all these findings together, it is conceivable that DR conducted in old age can be beneficial not only to retard age-related functional decline but also to restore functional activity in young rodents. Interestingly, recent evidence that involves DNA array gene expression analysis supports the findings on the age-related decrease in protein turnover and its reversion by late-onset DR.
- Overview of caloric restriction and ageing
It has been known for some 70 years that restricting the food intake of laboratory rats extends their mean and maximum life span. In addition, such life extension has been observed over the years in many other species, including mice, hamsters, dogs, fish, invertebrate animals, and yeast. Since this life-extending action appears to be due to a restricted intake of energy, this dietary manipulation is referred to as caloric restriction (CR). CR extends life by slowing and/or delaying the ageing processes. The underlying biological mechanism responsible for the life extension is still not known, although many hypotheses have been proposed. The Growth Retardation Hypothesis, the first proposed, has been tested and found wanting. Although there is strong evidence against the Reduction of Body Fat Hypothesis, efforts have recently been made to resurrect it. While the Reduction of Metabolic Rate Hypothesis is not supported by experimental findings, it nevertheless still has advocates. Currently, the most popular concept is the Oxidative Damage Attenuation Hypothesis; the results of several studies provide support for this hypothesis, while those of other studies do not. The Altered Glucose-Insulin System Hypothesis and the Alteration of the Growth Hormone-IGF-1 Axis Hypothesis have been gaining favor, and data have emerged that link these two hypotheses as one. Thus, it may now be more appropriate to refer to them as the Attenuation of Insulin-Like Signaling Hypothesis. Finally, the Hormesis Hypothesis may provide an overarching concept that embraces several of the other hypotheses as merely specific examples of hormetic processes. For example, the Oxidative Damage Attenuation Hypothesis probably addresses only one of likely many damaging processes that underlie aging. It is proposed that low-intensity stressors, such as CR, activate ancient hormetic defense mechanisms in organisms ranging from yeast to mammals, defending them against a variety of adversities and, when long-term, retarding senescent processes.
- Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells.
- Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction
Nicotinamide adenine dinucleotide (NAD)+-dependent sirtuins have been identified to be key regulators in the lifespan extending effects of calorie restriction (CR) in a number of species. In this study we report for the first time that promotion of the NAD+-dependent sirtuin, SIRT1-mediated deacetylase activity, may be a mechanism by which CR influences Alzheimer disease (AD)-type amyloid neuropathology. Most importantly, we report that the predicted attenuation of beta-amyloid content in the brain during CR can be reproduced in mouse neurons in vitro by manipulating cellular SIRT1 expression/activity through mechanisms involving the regulation of the serine/threonine Rho kinase ROCK1, known in part for its role in the inhibition of the non-amyloidogenic alpha-secretase processing of the amyloid precursor protein. Conversely, we found that the expression of constitutively active ROCK1 in vitro cultures significantly prevented SIRT1-mediated response, suggesting that alpha-secretase activity is required for SIRT1-mediated prevention of AD-type amyloid neuropathology. Consistently we found that the expression of exogenous human (h) SIRT1 in the brain of hSIRT1 transgenics also resulted in decreased ROCK1 expression and elevated alpha-secretase activity in vivo. These results demonstrate for the first time a role for SIRT1 activation in the brain as a novel mechanism through which CR may influence AD amyloid neuropathology. The study provides a potentially novel pharmacological strategy for AD prevention and/or treatment.
- Glucose, glycation and aging
Glycation, a deleterious form of post-translational modification of macromolecules has been linked to diseases such as diabetes, cataract, Alzheimer's, dialysis related amyloidosis (DRA), atherosclerosis and Parkinson's as well as physiological aging. This review attempts to summarize the data on glycation in relation to its chemistry, role in macromolecular damage and disease, dietary sources and its intervention. Macromolecular damage and biochemical changes that occur in aging and age-related disorders point to the process of glycation as the common event in all of them. This is supported by the fact that several age-related diseases show symptoms manifested by hyperglycemia. Free radical mediated oxidative stress is also known to arise from hyperglycemia. There is evidence to indicate that controlling hyperglycemia by antidiabetic biguanides prolongs life span in experimental animals. Caloric restriction, which appears to prolong life span by bringing about mild hypoglycemia and increased insulin sensitivity further strengthens the idea that glucose via glycation is the primary damaging molecule.
- Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems
Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR) extend lifespan and increase resistance to age-related diseases in rodents and monkeys and improve the health of overweight humans. Both IF and CR enhance cardiovascular and brain functions and improve several risk factors for coronary artery disease and stroke including a reduction in blood pressure and increased insulin sensitivity. Cardiovascular stress adaptation is improved and heart rate variability is increased in rodents maintained on an IF or a CR diet. Moreover, rodents maintained on an IF regimen exhibit increased resistance of heart and brain cells to ischemic injury in experimental models of myocardial infarction and stroke. The beneficial effects of IF and CR result from at least two mechanisms--reduced oxidative damage and increased cellular stress resistance. Recent findings suggest that some of the beneficial effects of IF on both the cardiovascular system and the brain are mediated by brain-derived neurotrophic factor signaling in the brain. Interestingly, cellular and molecular effects of IF and CR on the cardiovascular system and the brain are similar to those of regular physical exercise, suggesting shared mechanisms. A better understanding of the cellular and molecular mechanisms by which IF and CR affect the blood vessels and heart and brain cells will likely lead to novel preventative and therapeutic strategies for extending health span.
- The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans
We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species.
- Physiologic changes in humans subjected to severe, selective calorie restriction for two years in biosphere 2: health, aging, and toxicological perspectives
Biosphere 2 is a closed ecological space of 7-million cubic feet near Tucson, AZ, containing 7 biomes: rain forest, Savannah, ocean, marsh, desert, agricultural station, and habitat for humans and domestic animals. Sealed inside, 4 men and 4 women maintained themselves and the various systems for 2 years. All organic material, all water, and nearly all air was recycled, and virtually all food was grown inside. On the low calorie but nutrient-dense diet available, the men sustained 18% and the women 10% weight loss, mostly within the first 6 to 9 months. The nature of the diet duplicated rodent diets that had been shown to enhance health, lower disease incidence, and retard aging. Using blood specimens frozen at different points during and after the 2 years, determinations were made of a number of biochemical parameters judged to be pertinent based on past studies of rodents and monkeys on similar diets. These included blood lipids, glucose, insulin, glycosylated hemoglobin, renin, and others. The results clearly suggest that humans react to such a nutritional regime similarly to other vertebrates. In addition to these studies, and because this was a tightly closed, isolated environment, the levels of insecticides or pollutants or their derivatives were determined in the sera of 2 crew members. It was found that levels of the lipophilic toxicant DDE and the "total PCB" load increased with the loss of body fat during the first 12-18 months inside Biosphere 2, then decreased.
- Caloric restriction and aging as viewed from Biosphere 2
The low-calorie nutrient-dense diet consumed for 2 yr by the eight persons sealed inside the closed ecological space known as Biosphere 2, near Tucson, AZ, constituted a unique "experiment of nature," amounting to the first well-monitored application of a nutritional regimen proven in animals to substantially inhibit and delay time of onset of most age-related diseases, induce physiological changes characteristic of a functionally "younger" age, and extend both average and maximum lifespans. Over the 2 yr the eight persons demonstrated a substantial weight loss, remarkable fall in blood cholesterol, blood pressure, fasting blood sugar, and low white blood cell counts--exactly as seen in rodents on such a regimen. Studies in progress involving levels of cortisol, insulin, and glycosylated hemoglobin support the rodent similarity. Further studies will seek to determine whether additional among the large battery of physiologic changes induced in animals by caloric restriction are also induced in humans on a similar nutrient-dense, calorie-limited diet. Such evidence will pertain to the question whether the increased disease resistance and aging retardation shown by calorie-restricted rodents might also be expected to occur in humans.
- Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period
Four female and four male crew members, including two of the present authors (R. Walford and T. MacCallum)--seven of the crew being ages 27 to 42 years, and one aged 67 years--were sealed inside Biosphere 2 for two years. During seven eighths of that period they consumed a low-calorie (1750-2100 kcal/d) nutrient-dense diet of vegetables, fruits, nuts, grains, and legumes, with small amounts of dairy, eggs, and meat (approximately 12% calories from protein, approximately 11% from fat, and approximately 77% from complex carbohydrates). They experienced a marked and sustained weight loss of 17 +/- 5%, mostly in the first 8 months. Blood was drawn before entry into Biosphere 2, at many time-points inside it, and four times during the 30 months following exit from it and return to an ad libitum diet. Longitudinal studies of 50 variables on each crew member compared outside and inside values by means of a Bayesian statistical analysis. The data show that physiologic (e.g., body mass index, with a decrease of 19% for men and 13% for women; blood pressure, with a systolic decrease of 25% and a diastolic decrease of 22%), hematologic (e.g., white blood cell count, decreased 31%), hormonal (e.g., insulin, decreased 42%; T3, decreased 19%), biochemical (e.g., blood sugar, decreased 21%; cholesterol, decreased 30%), and a number of additional changes, including values for rT3, cortisol, glycated hemoglobin, plus others, resembled those of rodents or monkeys maintained on a calorie-restricted regime. Significant variations in several substances not hitherto studied in calorie-restricted animals are also reported (e.g., androstenedione, thyroid binding globulin, renin, and transferrin). We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets. With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.
- Changes in plasma lipids and lipoproteins in humans during a 2-year period of dietary restriction in Biosphere 2
Energy restriction was the major factor leading to low lipid and lipoprotein levels. Energy restriction with adequate nutrition of young and middle-aged people may substantially reduce risk for atherosclerosis and consequent coronary artery and cerebrovascular disease.
- Exercise-induced Modulation of Antioxidant Defense
Maintaining mobility is a critical element for the quality of life. Skeletal muscle, the primary organ for locomotion, undergoes age-associated deterioration in size, structure, and function.
- Can Exercise Training Improve Immune Function in the Aged?
Moderate exercise training has been shown to elicit beneficial outcomes in both the prevention and rehabilitation of many diseases of the elderly. It has been hypothesized that moderate levels of exercise improves, whereas strenuous exercise or overtraining suppresses, various immune function measures.
- Oxidative stress : relationship with exercise and training
Free radicals are reactive compounds that are naturally produced in the human body. They can exert positive effects (e.g. on the immune system) or negative effects (e.g. lipids, proteins or DNA oxidation). To limit these harmful effects, an organism requires complex protection - the antioxidant system. This system consists of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (e.g. vitamin E [tocopherol], vitamin A [retinol], vitamin C [ascorbic acid], glutathione and uric acid). An imbalance between free radical production and antioxidant defence leads to an oxidative stress state, which may be involved in aging processes and even in some pathology (e.g. cancer and Parkinson's disease). Physical exercise also increases oxidative stress and causes disruptions of the homeostasis. Training can have positive or negative effects on oxidative stress depending on training load, training specificity and the basal level of training. Moreover, oxidative stress seems to be involved in muscular fatigue and may lead to overtraining.
Maagdarmstoornissen: Candida infectie - Prikkelbaredarmsyndroom - Crohn - Colitus Ulcerosa - CVS/ME: Chronische vermoeidheid Syndroom - Diabetische complicaties: Bloeduiker stabilisatie - Neuropathie - Retinopathie - Nefropathie - Hart- en vaatziekten: Cardiomyopathie en Hartfalen - Hoge bloeddruk - Cholesterol verlaging - Aderverkalking (atherosclerose) - Spataderen - Levensverlenging: 100 jaren jong - DHEA - Melatonine - 65+ - Kanker: - Ondersteuningstherapie bij kanker - Bot en gewrichtsaandoeningen: - Artrose - Artritis - Osteoporose - Fibromyalgie: - Fibromyalgie - Urinewegaandoeningen: - Prostaatklachten - Blaasontsteking - Vrouwenklachten: Menopauze - Premenstrueelsyndroom - Overgewicht: - Overgewicht - SLIM - Oogaandoeningen: Staar - Slecht zien Andere artikelen: - HPU - Astma - Multiple Sclerose - Psoriasis - Depressie