Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet (original) (raw)

Aging and food restriction: Effect on lipids of cerebral cortex

Neurobiology of Aging, 1991

TACCONI, M. T., L. LLIGO/qA, M. SALMONA, N. PITSIKAS AND S. ALGERI. Aging and food restriction: Effect on lipids of cerebral cortex. NEUROBIOL AGING 12(1) 55-59, 1991.--In experimental animals dietary restriction reduces the body weight increase due to aging, increases longevity and delays the onset of age-related physiological deterioration, including age-related changes in serum lipids. Little is known about the influence of food restriction on brain lipids, whose concentration and composition have been shown to change with age. We studied whether some biochemical and biophysical parameters of rat brain membranes, known to be modified with age, were affected by a diet low in calories, in which 50% of lipids and 35% of carbohydrates have been replaced by fibers. The diet was started at weaning and maintained throughout the animal's entire life span. Animals fed the low calorie diet survived longer and gained less body weight than standard diet fed rats. Age-related increases in microviscosity, cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios were reduced or restored to the levels of young animals in cortex membranes of 32 old rats fed the low calorie diet, while the age-related increase in mono-to polyunsaturated fatty acid ratios in phospholipids was further raised. In conclusion we have shown that a diet low in calories and high in fibers affects lipid composition in the rat brain, in a direction opposite to that normally believed to reduce age-related deterioration of brain functions.

Effect of Initial Aging and High-Fat/High-Fructose Diet on Mitochondrial Bioenergetics and Oxidative Status in Rat Brain

Molecular Neurobiology, 2019

Middle age is an early stage of the aging process, during which the consumption of diets rich in saturated fats and/or simple sugars might influence brain function, but only few data are available on this issue. We therefore investigated the impact of a diet rich in saturated fat and fructose (HFF) on mitochondrial physiology in hippocampus and frontal cortex of middle-aged rats (1 year old), by including a group of adult rats (90 days) as a Bnegative control,^lacking the putative effect of aging. Middle-aged rats were fed HFF or control diet for 4 weeks. Mitochondrial function was analyzed by high-resolution respirometry and by assessing the amount of respiratory complexes. Markers of oxidative balance, as well as the protein content of uncoupling protein 2 (UCP2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and peroxisome proliferator-activated receptor alpha (PPARα), were also assessed. A decrease in the activity of complex I was detected in both brain areas of middle-aged rats. In hippocampus, mitochondrial respiratory capacity and complex IV content decreased with age and increased with HFF diet. Higher protein oxidative damage, decreased antioxidant defenses, and increased UCP2 and PGC-1α content were found in hippocampus of middle-aged rats. HFF feeding induced a significant reduction in the amount of UCP2, PGC-1α, and PPARα, together with higher protein oxidative damage, in both brain areas. Overall, our results point to middle age as a condition of early brain aging for mitochondrial function, with hippocampus being an area more susceptible to metabolic impairment than frontal cortex.

The aging brain - molecular and metabolic changes

Biologia Serbica, 2017

Aging is a complex set of events that involves the whole body. However, disruption of the central nervous system (CNS) function is the aspect of aging that elderly people worry about most. Aging has different effects on different aspects of neurological function. Our knowledge of the basic molecular mechanism of brain aging has significantly improved over the past few decades. The rate of aging is not fixed, but is plastic and subject to modifications. The environmental factor proven to be very potent in modulating aging is reduced dietary intake. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay ageing and increase an active and healthy lifespan in diverse species, from yeast to mammals. Additionally, DR can improve various brain functions, including learning and memory, synaptic plasticity and neurogenesis.

Effect of Carbohydrate Type on Brain Composition and Senescence in Aging, Hyperinsulinemia-prone OBESE LA/Ntul//-cp Rats

Asian Journal of Medicine and Health

To determine if phenotype and the carbohydrate type resulted in alterations in brain composition in the obese phenotype of the congenic LA/Ntul//-cp rat, groups (n= 8 rats/group) of male littermate lean and obese rats were fed standardized isocaloric diets containing 54% (w/w) cornstarch (ST diet) or 54% (w/w) sucrose (SUC diet) from 1 until 10.5 ± 0.5 months of age. The obese phenotype of his strain develops early onset chronic hyperinsulinemia without NIDDM associated with hypertrophic-hyperplastic obesity during early postweaning growth. Brain tissues were dissected, and representative aliquots subjected to total fat, protein, and DNA analysis. Body weights of obese >> lean and were greater when fed the SUC than the ST diet in both phenotypes. Brain mass of lean > obese, and diet was associated with modestly lower brain weights in rats fed the SUC than the ST diet. Brain total Protein and DNA content of lean rats were > obese rats and were modestly Lower in SUC than S...

Caloric restriction and redox homeostasis in various regions of aging male rat brain: Is caloric restriction still worth trying even after early-adulthood?

Journal of Food Biochemistry, 2018

Aging is generally considered as a major risk factor in the etiology and/ or progression of neurodegenerative diseases; namely, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, and amyotrophic lateral sclerosis (Hindle, 2010; Niccoli & Partridge, 2012). Pathophysiological alterations leading to these morbidities do not take place in a short period of time and they tend to involve longterm neurometabolic dysregulation (Gao & Hong, 2008). Therefore, the aforementioned disorders are said to be "age"-related and are currently seen as "natural" consequences of biological aging process. Etiology and effects of brain aging are known to be multifactorial and they involve many intrinsic factors including degenerative alterations in neuronal network, vasculature, signal transduction mechanisms,

(n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats

The Journal of nutrition, 2005

The altered neuron activity of rats deficient in (n-3) PUFAs may be due in part to a decrease in brain glucose utilization and glucose transport. We measured the glucose transporter protein GLUT1 isoforms at the blood-brain barrier (55-kDa) and in astrocytes (45-kDa) by Western immunoblotting and their mRNA by real time RT-PCR analysis in the cerebral cortex of adult male rats fed diets lacking (n-3) fatty acids (1st generation). The neuron glucose transporter GLUT3 was also assayed. The fatty acids in the phosphatidylcholine (PC), ethanolamine phosphoglycerolipid (EPG), and phosphatidylserine (PS) fractions of isolated microvessels and homogenates of the cerebral cortex were determined. The levels of (n-6) PUFAs [mainly arachidonic acid, 20:4(n-6)] in the phospholipid fractions of microvessels were higher and the levels of (n-3) PUFAs [mainly docosahexaenoic acid, 22:6(n-3)] were lower than in cerebral cortex homogenates. The microvessels and cortex of rats fed the (n-3) PUFA-defic...

Age-related changes in metabolic profiles of rat hippocampus and cortices

European Journal of Neuroscience, 2010

The time course of metabolic changes was investigated in the hippocampus and the parietal, rhinal and frontal cortices of rats from 4 to 30 months old. Samples were analysed by the solid-state high-resolution magic angle spinning nuclear magnetic resonance method. Quantification was performed with the quest procedure of jmrui software. Eighteen metabolites were identified and separated in the spectrum. Six of them were not age sensitive, in particular alanine, glutamine and lactate. In contrast, choline, glycerophosphocholine, myo-inositol, N-acetylaspartate, scyllo-inositol (s-Ins) and taurine (Tau) were notably altered over aging. Interestingly, each age group showed a specific metabolic profile. The concentration of metabolites such as Tau was altered in middle-aged rats only, whereas the sIns level decreased in old rats only. Most metabolites showed progressive alteration during the process of aging, which was initiated during the middle-aged period (18 months). Taken together, these results suggest that cell membrane integrity is perturbed with age. Each brain region investigated had distinctive qualitative and ⁄ or quantitative metabolic age-related features. These age-related changes would affect network connectivities and then cognitive functions.

Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids

Journal of Neurochemistry, 2002

Long-chain polyunsaturated (n-3) fatty acids have been reported to influence the efficiency of membrane receptors, transporters and enzymes. Because the brain is particularly rich in docosahexaenoic acid (DHA, 22:6 n-3), the present study addresses the question of whether the 22:6 n-3 fatty acid deficiency induces disorder in regulation of energy metabolism in the CNS. Three brain regions that share a high rate of energy metabolism were studied: fronto-parietal cortex, hippocampus and suprachiasmatic nucleus. The effect of the diet deficient in n-3 fatty acids resulted in a 30-50% decrease in DHA in membrane phospholipids. Moreover, a 30% decrease in glucose uptake and a 20-40% decrease in cytochrome oxidase activity were observed in the three brain regions. The n-3 deficient diet also altered the immuno-reactivity of glucose transporters, namely GLUT1 in endothelial cells and GLUT3 in neurones. In n-3 fatty acid deficient rats, GLUT1-immunoreactivity readily detectable in microvessels became sparse, whereas the number of GLUT3 immunoreactive neurones was increased. However, western blot analysis showed no significant difference in GLUT1 and GLUT3 protein levels between rats deficient in n-3 fatty acids and control rats. The present results suggest that changes in energy metabolism induced by n-3 deficiency could result from functional alteration in glucose transporters.

Effect of Age and Caloric Intake on Protein Oxidation in Different Brain Regions and on Behavioral Functions of the Mouse

Archives of Biochemistry and Biophysics, 1996

The objective of this study was to determine if oxidative stress/damage is a possible causal factor in the senescence-related loss of brain functions in the mouse. If such a relationship indeed existed, it was expected that oxidative protein damage would increase with age within regions of the brain associated with senescence-related functional loss, and that calorie restriction, an intervention which retards certain aspects of age-associated functional loss, would reverse such increases. Dietary restriction was found to retard age-associated decline of sensorimotor coordination and improve performance of aged mice on an avoidance learning problem. Protein carbonyl concentration, one measure of protein oxidation, increased from 8 to 27 months of age in most regions of the mouse brain, with the most notable increases occurring in the striatum and hippocampus, regions of the brain strongly implicated in age-associated functional loss. Age-associated loss of protein sulfhydryls was more uniform across brain regions and did not involve the hippocampus. Dietary restriction resulted in reversal of the age-associated regional trends in carbonyl and sulfhydryl concentration, with the largest changes occurring within the striatum. Cross over studies in aged calorie restricted andad libitumfed mice indicated that lowering of carbonyl content by calorie restriction could be induced or reversed within a time frame of 3 to 6 weeks. These findings suggest that the beneficial effects of dietary restriction upon brain function and life span may depend upon its ability to acutely reduce steady-state levels of oxidative stress.