scholarly journals Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4526
Author(s):  
Vesna Tesic ◽  
Jelena Ciric ◽  
Irena Jovanovic Macura ◽  
Nevena Zogovic ◽  
Desanka Milanovic ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Food Restriction ◽  
Corticosterone Level ◽  
Negative Regulator ◽  
Beneficial Effects ◽  
Age Related ◽  
Old Rats ◽  
Short And Long Term ◽  
Apoptotic Effects

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.

scholarly journals Effect of long-term food restriction on cardiac mechanics

1997 ◽  
Vol 273 (5) ◽  
pp. H2333-H2342 ◽  
Author(s):  
Simon Klebanov ◽  
Jeremiah T. Herlihy ◽  
Gregory L. Freeman
Keyword(s):  
Food Restriction ◽  
Relaxation Times ◽  
Cardiac Mechanics ◽  
Low Calcium ◽  
Age Related ◽  
Pressure Development ◽  
Short And Long Term ◽  
Ad Libitum ◽  
Contraction And Relaxation

Food restriction (FR) is the only known intervention capable of increasing mammalian life span. It not only increases longevity, but reduces the incidence of a broad spectrum of age-related pathologies, including cardiomyopathy, and retards the physiological decline associated with aging. Previous work from this laboratory has shown that long-term FR affects the contractile machinery of the heart, shifting the cardiac myosin profile from the fast, V1 isoform to the slow, V3 isoform. The aim of the present study was to determine whether FR also induces changes in cardiac mechanics. Isolated, isovolumically beating hearts were examined from four groups of rats: 1) ad libitum-fed rats killed at 10–13 mo of age, 2) FR rats offered only 60% of the calories consumed by ad libitum-fed rats and killed at the same age, 3) young ad libitum-fed rats having the same heart weights as the FR rats, and 4) ad libitum-fed rats subjected to short-term FR, i.e., for the last 3 wk of life, and also killed at 10–13 mo of age. Both short- and long-term FR profoundly and to approximately the same extent affected cardiac mechanics. Hearts from FR rats developed much higher pressures than hearts from the ad libitum-fed rats under conditions of low-calcium perfusate. This difference disappeared, however, when contractility was enhanced by either calcium or isoproterenol. FR prolonged both contraction and relaxation times. Long-term ad libitum-fed rats (adult, 10–13 mo of age) had a lower isoproterenol sensitivity than the young ad libitum-fed rats (10 wk of age). Both short- and long-term FR restored the sensitivity to isoproterenol. In summary, FR profoundly affects many aspects of cardiac mechanics, enhancing some age-related changes (prolongation of the contraction and relaxation times), attenuating another (increasing the isoproterenol sensitivity), and, finally, inducing some unique changes unrelated to age (increased pressure development under low-calcium perfusate).

scholarly journals Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

2014 ◽  
pp. 309 ◽  
Author(s):  
Cristovam Picanço-Diniz ◽  
Thais Cristina Galdino De Oliveira ◽  
Fernanda Cabral Soares ◽  
Liliane Dias E Dias De Macedo ◽  
Domingos Luiz Wanderley Picanco Diniz ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Long Term Care ◽  
Cognitive Stimulation ◽  
Term Care ◽  
Beneficial Effects ◽  
Age Related ◽  
Age Related Cognitive Decline

scholarly journals Gut Microbiota Is Involved in Alcohol-Induced Osteoporosis in Young and Old Rats Through Immune Regulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Cheng ◽  
Bo Tan ◽  
Xiaojing Wu ◽  
Feng Liao ◽  
Fei Wang ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Gut Microbiota ◽  
Bone Metabolism ◽  
Alcohol Metabolism ◽  
Excessive Alcohol Consumption ◽  
Young Rats ◽  
Age Related ◽  
Different Ages ◽  
Old Rats

Long-term and excessive alcohol consumption are risk factors for osteoporosis. Excessive drinking can reduce bone density and also cause imbalance of gut microbiota. And gut microbiota can affect bone metabolism through various mechanisms, and the regulation of gut microbiota is closely related to age. However, the effects of gut microbiota on alcohol-induced osteoporosis at different ages are unclear. In this study, young and old rats were used to induce osteoporosis by long-term alcohol consumption, and alcohol metabolism, bone morphology, bone absorption and immune activity of rats were analyzed to determine the effects of alcohol on rats of different ages. In addition, changes of gut microbiota in rats were analyzed to explore the role of gut microbiota in alcohol-induced osteoporosis in rats of different ages. The results showed the ability of alcohol metabolism was only associated with age, but not with alcohol consumption. Long-term alcohol consumption resulted in the changes of bone metabolism regulating hormones, bone loss, activation of receptor activator of NF-κB ligand (RANKL) signaling and inflammatory response. And osteoporosis was more severe in old rats than young rats, suggesting that alcohol-induced osteoporosis is age-related. In addition, long-term drinking also affected the composition of gut microbiota in rats, with a significant increase in the proportion of pro-inflammatory microorganisms. Overall, this study found that long-term alcohol consumption induced osteoporosis and affected the composition of gut microbiota. And alcohol can activate T lymphocytes directly or indirectly by regulating the changes of gut microbiota to produce cytokines, and further activate osteoclasts. In addition, the osteoporosis was more severe in the old rats than young rats, which may be due to the higher diversity and stronger regulation ability of gut microbiota in young rats compared with old rats.

Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2

2001 ◽  
Vol 281 (6) ◽  
pp. F1123-F1131 ◽  
Author(s):  
S. Combet ◽  
L. Teillet ◽  
G. Geelen ◽  
B. Pitrat ◽  
R. Gobin ◽  
...  
Keyword(s):  
Food Restriction ◽  
Marked Decrease ◽  
Collecting Duct ◽  
Apical Region ◽  
Principal Cells ◽  
Aquaporin 2 ◽  
Age Related ◽  
Old Rats ◽  
Ad Libitum ◽  
Chronic Food Restriction

First published August 8, 2001; 10.1152/ajprenal.00139.2001.—The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 (AQP2) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both AQP2 and the phosphorylated form of AQP2 (p-AQP2), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin (AVP) was similar in 10- and 30-mo-old rats fed ad libitum, but was doubled in food-restricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in AQP2, UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of AQP2 and p-AQP2 to the apical membrane in inner medulla principal cells, permitted by increased plasma AVP concentration.

scholarly journals Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

2009 ◽  
Vol 297 (3) ◽  
pp. H1087-H1095 ◽  
Author(s):  
Lori S. Kang ◽  
Rafael A. Reyes ◽  
Judy M. Muller-Delp
Keyword(s):  
Superoxide Dismutase ◽  
Hydroxyl Radical ◽  
Immunoblot Analysis ◽  
Radical Formation ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Age Related ◽  
Old Rats ◽  
Coronary Arterioles ◽  
Reduced Flow

Aging contributes significantly to the development of cardiovascular disease and is associated with elevated production of reactive oxygen species (ROS). The beneficial effects of nitric oxide (NO)-mediated vasodilation are quickly abolished in the presence of ROS, and this effect may be augmented with aging. We previously demonstrated an age-induced impairment of flow-induced dilation in rat coronary arterioles. Therefore, the purpose of this study was to determine the effects of O2− scavenging, as well as removal of H2O2, the byproduct of O2− scavenging, on flow-mediated dilation in coronary resistance arterioles of young (4 mo) and old (24 mo) male Fischer 344 rats. Flow increased NO and H2O2 production as evidenced by enhanced diaminofluorescein and dichlorodihydrofluorescein fluorescence, respectively, whereas aging reduced flow-induced NO and H2O2 production. Endothelium-dependent vasodilation was evaluated by increasing intraluminal flow (5–60 nl/s) before and after treatment with the superoxide dismutase mimetic Tempol (100 μM), the H2O2 scavenger catalase (100 U/ml), or Tempol plus catalase. Catalase reduced flow-induced dilation in both groups, whereas Tempol and Tempol plus catalase diminished vasodilation in young but not old rats. Tempol plus deferoxamine (100 μM), an inhibitor of hydroxyl radical formation, reversed Tempol-mediated impairment of flow-induced vasodilation in young rats and improved flow-induced vasodilation in old rats compared with control. Immunoblot analysis revealed increases in endogenous superoxide dismutase, catalase, and nitrotyrosine protein levels with aging. Collectively, these data indicate that NO- and H2O2-mediated flow-induced signaling decline with age in coronary arterioles and that elevated hydroxyl radical formation contributes to the age-related impairment of flow-induced vasodilation.

scholarly journals Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats

2000 ◽  
Vol 11 (8) ◽  
pp. 1488-1497
Author(s):  
LAURENT TEILLET ◽  
PHILIPPE VERBEKE ◽  
SABINE GOURAUD ◽  
HILAIRE BAKALA ◽  
CAROLINE BOROT-LALOI ◽  
...  
Keyword(s):  
Food Restriction ◽  
Structure And Function ◽  
Female Rats ◽  
Advanced Glycation ◽  
Age Related ◽  
Glycation End Products ◽  
Old Rats ◽  
Cardiovascular Systems ◽  
And Function ◽  
Chronic Food Restriction

Abstract.Tissue content of advanced glycation end products (AGE) increases with age and contributes to the changes in structure and function of the renal and cardiovascular systems. The effect of chronic food restriction on this AGE accumulation was investigated in lean WAG/Rij rats. A 30% food restriction performed from 10 to 30 mo in female rats reduced their mean body weight from 240 ± 7 to 160 ± 12 g, but did not modify their survival. AGE collagen content increased from 14.3 ± 5.5 to 104.7 ± 13.0 arbitrary units per microgram (AU/μg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from 9.7 ± 1.2 to 310.6 ± 34.6 AU/μg OHPro in the abdominal aorta. Food restriction reduced AGE accumulation to 21.4 ± 3.3 and 74.6 ± 16.5 AU/μg OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for collagen prepared from isolated glomeruli (7.8 ± 1.2, 81.2 ± 16.1, and 10.3 ± 4.3 AU/μg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats). Reduction of intrarenal and arterial AGE accumulation by food restriction was confirmed by immunostaining in optical microscopy. Age-related changes in arterial and kidney structures as polyuria and proteinuria were mainly prevented by food restriction. These data indicate that chronic food restriction reduces the accumulation of AGE and preserves the structure and function of the renal and cardiovascular systems in learn rats, although it did not affect survival of the animals between 10 and 30 mo.

scholarly journals A Computational Solution to Bolster Epigenetic Clock Reliability for Clinical Trials and Longitudinal Tracking

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 5-5
Author(s):  
Albert Higgins-Chen ◽  
Kyra Thrush ◽  
Tina Hu-Seliger ◽  
Yunzhang Wang ◽  
Sara Hagg ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Reliability ◽  
Principal Component ◽  
Epigenetic Clock ◽  
Age Related ◽  
Longitudinal Tracking ◽  
Short And Long Term ◽  
Epigenetic Biomarker ◽  
Computational Solution

Abstract Epigenetic clocks are widely used aging biomarkers, but they are calculated from methylation data for individual CpGs that can be surprisingly unreliable. We report that technical noise causes six major epigenetic clocks to deviate by 3 to 9 years between replicates. We present a novel computational solution: we perform principal component analysis followed by biological age prediction using principal components, extracting shared age-related changes across CpGs while ignoring noise from individual CpGs. Our novel principal-component versions of six clocks show agreement between most technical replicates within 1 year, and increased stability in short- and long-term longitudinal studies. This requires only one additional step compared to traditional clocks, does not require prior knowledge of CpG reliabilities, and can improve the reliability of any existing or future epigenetic biomarker. The extremely high reliability of principal component epigenetic clocks makes them particularly useful for personalized medicine and clinical trials evaluating novel aging interventions.

scholarly journals Neuroprotective Effects of a Combined Therapy With Memantine, Donepezil and Vitamin D in Ovariectomized Female Mice Subjected to Dementia Model

2021 ◽  
Author(s):  
Ana Daniela Coutinho Vieira ◽  
Eduarda Behenck Medeiros ◽  
Gabriel Casagrande Zabot ◽  
Nathalia de Souza Pereira ◽  
Natália Baltazar do Nascimento ◽  
...  
Keyword(s):  
Vitamin D ◽  
Combined Therapy ◽  
Neuroprotective Effects ◽  
Female Mice ◽  
Beneficial Effects ◽  
Gfap Immunoreactivity ◽  
Short And Long Term ◽  
Triple Treatment ◽  
Inflammation Parameters

Abstract The postmenopausal period is characterized by a decrease in the hormonal supply which is associated with Alzheimer's Disease (AD). Vitamin D is neuroprotective and can be used in combination with pre-existing medications to improve its effects. The objective was to evaluate the effect of vitamin D associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for 5 months and subjected to an AD-induced dementia model. Animals were divided into 5 groups who received 17 days of treatment and were subjected to behavioral tests. The animals underwent euthanasia at 18th day. OVX groups exhibit reduced levels of E2 and triple treatment group had high levels of vitamin D. The induction of dementia with OVX induced short- and long-term spatial and habituation memories damage. Also, induced reduction of BDNF and IL-4 levels in hippocampus, and increasing levels of TNFα in hippocampus and of IL-1β in hippocampus and frontal cortex of animals, as well as a significant increase on GFAP immunoreactivity. Triple-association treatment reversed the effects of long-term spatial and habituation memories damage, as well as reversed changes in TNFα, IL-1β, IL-4 and GFAP immunoreactivity levels in hippocampus of treated animals. Therapeutic association has beneficial effects on memory and inflammation parameters in female mice subjected to OVX and the AD animal model of dementia.

Working Memory Training From an Individual Differences Perspective

2019 ◽  
pp. 14-39
Author(s):  
Erika Borella ◽  
Barbara Carretti ◽  
Cesare Cornoldi ◽  
Rossana De Beni
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Task Demands ◽  
Memory Training ◽  
Training Procedure ◽  
Adaptive Procedure ◽  
Age Related ◽  
Short And Long Term ◽  
Underlying Processes

This chapter presents and discusses a verbal WM training developed for older adults. The model of working memory (WM) proposed by Cornoldi and Vecchi, which is based on an analysis of individual and age-related differences, is used as a framework for discussing the efficacy of the WM training procedure proposed and developed for older adults. The model (a) assumes that different WM tasks (and underlying processes) may be located along two continua that describe the type of content to be processed and the degree of active control required by the task and (b) considers metacognitive/motivational aspects, which also have a role in determining WM performance. The WM training procedure presented here takes into account not only the capacity to use WM resources and attentional control by adopting an adaptive procedure, but also the importance of including variations in the training task demands to produce a challenging and engaging task that sustains motivation and favor the training’s short- and long-term efficacy, at least in older adults. These aspects seem crucial in explaining the results obtained with this verbal WM training program in aging.

Modulation of central glucocorticoid receptors in short- and long-term experimental hypothyroidism

2015 ◽  
Author(s):  
Elena Nikolopoulou ◽  
Dimitris Mytilinaios ◽  
Dimitris Spinos ◽  
Nikitas – Apollon Panagiotopoulos ◽  
George P. Chrousos
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Affinity ◽  
Glucocorticoid Receptors ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Receptor Number ◽  
Short And Long Term

Aim: Normal adrenocortical responsiveness to stress involves glucocorticoid negative feedback to terminate hypothalamic-pituitary-adrenal (HPA) axis activation. Hypothyroidism is associated with a centrally mediated adrenal insufficiency associated. The aim of this study was to examine whether this may be explained by a disturbed glucocorticoid feedback through specific brain receptors: the mineralocorticoid (MR) and glucocorticoid receptor (GR). Methods: Cytosolic receptor binding and gene expression was assessed in male Sprague-Dawley rats (350gm) with short- (7 days) and long-standing (60 days) hypothyroidism (thyroidectomy). Glucocorticoid receptor number and binding affinity in the hippocampus were measured using radioreceptor assay. In situ hybridization was employed to examine GR and MRmRNA levels in the hippocampus and the pituitary. Results: No differences in receptor number or affinity were observed after 7days and 60days treatment. Increased GRmRNA expression in the anterior pituitary was observed in 7day hypothyroid rats under basal conditions compared to euthyroid rats (122.77+4.93 vs 99.65+4.83 DPM/mg; p<0.05), which was associated with significantly decreased GRmRNA levels after osmotic stress (100.82+2.8 vs 110.48+4.1 DPM/mg; p<0.05). No differences were observed at 60days. No effect on MR mRNA expression in the hippocampus was seen in basal condition after both 7- and 60days hypothyroidism. MRmRNA was significantly decreased in 60 days-hypothyroid rats compared to euthyroid after normal saline (3995.67+131.54 vs 5121.00+505.2 DPM/mg; p<0.05). Conclusion: Hypothyroidism resulted in significant changes in GR and MR mRNA levels, in the hippocampus and the pituitary, without changes in receptor number and binding affinity.

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