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International audience; Wistar rats were fed during 6 months with 33% maize, either non genetically modified or containing MON810 or NK603 (11% and 33%). Extensive chemical analysis by MS and NMR profiling and targeted analyses were undertaken to qualify the harvests and quantify in maize and pellets macro- and micronutrients, anti-nutrients and undesirable substances and contaminants. All diets contained low levels (50 to 100 fold lower than the MRL values) of undesirable substances. Thirty rats per gender were fed with 8 different diets: MON810 (11% and 33%) plus isogenic control, NK603 (11% and 33% ± glyphosate treatment) and isogenic control. Rats were sacrificed after 3 months (sub-group A, 10 rats per diet, per gender) and 6 months (sub-group B, 12 rats and C, 8 rats per diet, per gender). Urine were collected in metabolic cages and blood at 90 (sub-group A), 90/135/180 (sub-group B) and 180 days of feeding (sub-group C). In addition to classical toxicological analysis we performed metabolomics and hormones quantification in blood and urine, transcriptomics on liver and kidney, gut barrier analysis, kidney and gonads targeted immunohistology. Statistical analyses were conducted first blindly and thereafter on the basis of relevant pair-wise comparison. We easily discriminate the rat gender or maize origin. Among the numerous statistically significant differences in pair-wise comparisons some concerned GMO and non-GMO, but no biological relevance could be established due to the lack of differences in biologically linked variables, dose-response effects or clinical disorders.

Analytical methods for food control are mainly focused on restricted lists of well-known contaminants. This paper shows that liquid chromatography-high-resolution mass spectrometry (LC/ESI-HRMS) associated with the data mining tools developed for metabolomics can address this issue by enabling (i) targeted analyses of pollutants, (ii) detection of untargeted and unknown xenobiotics, and (iii) detection of metabolites useful for the characterization of food matrices. A proof-of-concept study was performed on 76 honey samples. Targeted analysis indicated that 35 of 83 targeted molecules were detected in the 76 honey samples at concentrations below regulatory limits. Furthermore, untargeted metabolomic-like analyses highlighted 12 chlorinated xenobiotics, 1 of which was detected in lavender honey samples and identified as 2,6-dichlorobenzamide, a metabolite of dichlobenil, a pesticide banned in France since 2010. Lastly, multivariate statistical analyses discriminated honey samples according to their floral origin, and six discriminating metabolites were characterized thanks to the MS/MS experiments.

This work aimed at establishing the relevance of using the in vivo model of cyclophosphamide (CYP)-induced bladder inflammation in rats for in vivo pharmacological studies. Specifically, we measured visceral nociception, identified key inflammatory mediators and evaluated the effects of relevant pharmacological treatments. Cystitis was induced in female rats by a single CYP injection. Sensitivity of the lower abdomen to von Frey mechanical stimulation was determined as a nociceptive parameter. Bladders were assessed for weight, wall thickness and macroscopic damage. Inflammatory mediators were quantified in bladders and urines. The effects of aspirin, ibuprofen and morphine were investigated on all these parameters. A single CYP injection increased nociceptive scores and decreased nociceptive threshold in response to mechanical stimuli between 1 and 4h post-administration. Increased bladder weight and wall thickness were associated with edema and hemorrhage. Bladder levels of IL-1β, IL-6, MCP-1 and VCAM, and urinary levels of PGE2 were increased. In contrast, a decrease in the urinary metabolites, indoxyl sulfate and pantothenic acid, was observed. Aspirin, ibuprofen and morphine decreased CYP-induced referred visceral pain. Aspirin and ibuprofen also reversed the increased wall thickness, macroscopic damage and levels of IL-1β, IL-6 and PGE2, and the decreased panthotenic acid levels. In contrast, morphine increased wall thickness, edema, hemorrhage, and bladder IL-6 and MCP-1 levels. This work presents a new and reliable method to evaluate visceral sensitivity in rats, and new relevant biomarkers identified in the bladder and urine to measure inflammation and pain parameters for in vivo pharmacological studies.

Renal failure in the elderly is currently underestimated and presents a real challenge for the public health system. Kidney function must be routinely assessed by creatinine clearance, estimated with either the Cockcroft and Gault formula or the simplified MDRD formula, which appears especially appropriate for the elderly. Normal kidney aging is related to tissue and functional changes that make older patients very vulnerable to environmental modifications. Numerous factors can accelerate the impairment of rental function during aging. Some of them cannot be modified: sex, genome, and initial kidney disease. Most of them can be managed or treated: hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, proteinuria, and the presence of oxidation and glycation products. Chronic renal failure in the elderly must be managed early with strict treatment targets to avoid the development of end-stage renal disease. Inhibitors of the renin-angiotensin-aldosterone system play an essential role in optimizing nephroprotection: control of hypertension, diabetes complications, and proteinuria. They should be prescribed very carefully in older patients. Age is not a prerequisite for consultations with nephrologists, which should take place early so that nephroprotection can still be useful.

Pour reussir son vieillissement en restant en bonne sante et autonome le plus longtemps possible, un mode de vie sain evitant les facteurs de risque des grandes pathologies doit etre adopte precocement et maintenu. Il n’est toutefois jamais trop tard pour bien faire. Modifier des comportements meme tardivement peut s’averer benefique pour la sante. Les differents travaux resumes dans cet article montrent que les personnes qui reduisent leurs facteurs de risque vieillissent en meilleure sante, retardent la survenue de la dependance et changent leur mode de consommation de soins. Ces actions de promotion visant a ameliorer les comportements positifs peuvent etre ciblees sur certains aspects de la sante, tels que la nutrition, l’activite physique, le sommeil, la prise de medicaments ou etre integrees dans des programmes globaux couvrant plusieurs de ces domaines.

A data fusion approach was applied to a commercial honey data set analysed by (1)H-nuclear magnetic resonance (NMR) 400 MHz and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The latter was performed using two types of mass spectrometers: an Orbitrap-MS and a time of flight (TOF)-MS. Fifty-six honey samples from four monofloral origins (acacia, orange blossom, lavender and eucalyptus) and multifloral sources from various geographical origins were analysed using the three instruments. The discriminating power of the results was examined by PCA first considering each technique separately, and then combining NMR and LC-HRMS together with or without variable selection. It was shown that the discriminating potential is increased through the data fusion, allowing for a better separation of eucalyptus, orange blossom and lavender. The NMR-Orbitrap-MS and NMR-TOF-MS mid-level fusion models with variable selection were preferred as a good discrimination was obtained with no misclassification observed for the latter. This study opens the path to new comprehensive food profiling approaches combining more than one technique in order to benefit from the advantages of several technologies. Graphical Abstract Data fusion between high resolution 1H-NMR and mass spectrometry.

Screening of a large number of emerging pollutants is highly desirable for the control of water quality. In this respect, a novel, fully automated contaminant screening method based on an integrated sample preconcentration and liquid chromatography coupled to high resolution mass spectrometry (SPE-UHPLC-HRMS) has been developed. The optimal chromatographic column and experimental conditions allowing the retention and subsequent elution of the maximum number of analytes were defined. Liquid chromatography and Q-exactive (Orbitrap (TM)) parameters were optimized to obtain the best separation of molecules of interest, and the lowest detection limits. Due to the large amount of data to compare, a script written in R language was developed to evaluate the quality of the data generated by the comparison of 14 experimental conditions. The developed method enables the simultaneous semi quantitative analysis of 539 compounds (pesticides and drug residues), in 36 min with only 5 mL of water. Method validation was achieved through studies of repeatability, selectivity, linearity and matrix effect. Application to 20 tap water samples collected in and around Paris showed the presence of 34 different compounds all with concentrations below 0.1 mu g/L, the European Union limit for drinking water. Pesticides and transformation products frequently found in water resources such as atrazine and its metabolites, hexazinone, oxadixyl, propazine and simazine were detected. Drug residues such as valsartan and carbamazepine, usually not monitored, were also found. The next step will be to assess the ability of this method to highlight the presence of unexpected contaminants not present in our database. (C) 2016 Elsevier Ltd. All rights reserved.

Summary Introduction The prevalence of sleep disorders increases with age and reaches 20 to 40% of those older than 60 years. We set up a health education program to help the elderly to improve their sleep. It includes a preliminary 9-day evaluation with a sleep diary and wrist actigraph, a day of group cognitive behavioral therapy, and a follow-up assessment, again with sleep diary and actigraph. Methods Of the 26 study participants (9 men and 17 women, mean age: 68 ± 1 years), 14 had insomnia with night awakenings of 1 hour or longer or a sleep latency of 30 minutes or longer or both (group 1). The other 12 (group 2) also complained of insufficient sleep. Results In the weeks following cognitive behavioral therapy, group 1 improved their total sleep time by an average of 24 to 33 minutes, with reduced night-time awakenings and sleep latency and no change in their time spent in bed. Those in group 2 also increased their total sleep time by 18 to 47 minutes, by spending more time in bed and maintaining a sleep efficiency close to 88%. Conclusion This study showed that cognitive behavioral therapy coupled with individual sleep evaluation improves sleep duration in elderly people who complain of insufficient sleep. These beneficial effects were accompanied by positive assessments of both subjective sleep quality and morning energy.

Le nombre de personnes qui ne sont pas satisfaites de leur sommeil s’accroit avec l’âge. La difficulte a s’endormir, les reveils nocturnes frequents et durables, l’eveil precoce le matin sont courants apres 60 ans. La consommation de somniferes augmente en parallele dans cette tranche d’âge, au risque d’induire des effets secondaires importants. Et pourtant les modifications de la structure du sommeil reellement liees au vieillissement physiologique sont discretes. Ces troubles peuvent souvent s’ameliorer avec une bonne hygiene du sommeil, une alimentation adaptee, une exposition suffisante a la lumiere et une activite physique. Il n’en reste pas moins vrai que certaines pathologies susceptibles de perturber le sommeil sont plus frequentes chez les seniors. Il convient de les diagnostiquer et de les traiter au mieux. En effet, un sommeil de mauvaise qualite et l’installation d’insomnies chroniques ont des effets nefastes sur les fonctions cognitives, l’humeur, la qualite de vie et plus generalement la sante des seniors et de leur entourage.

Aging is commonly associated with defective urine-concentrating ability. The present study examined how the kidney and the brain of senescent (30-mo-old) female WAG/Rij rats respond to dehydration induced by 2 days of water deprivation in terms of urea transporter (UT) regulation. In euhydrated situation, senescent rats exhibited similar vasopressin plasma level but lower urine osmolality and papillary urea concentration and markedly reduced kidney UT-A1, UT-A3, and UT-B1 abundances compared with adult (10-mo-old) rats. Senescent rats responded to dehydration similarly to adult rats by a sixfold increase in vasopressin plasma level. Their papillary urea concentration was doubled, without, however, attaining that of dehydrated adult rats. Such an enhanced papillary urea sequestration occurred with a great fall of both UT-A1 and UT-A3 abundances in the tip of inner medulla and an increased UT-A1 abundance in the base of inner medulla. UT-A2 and UT-B1 were unchanged. These data suggest that the inability of control and thirsted senescent rats to concentrate urine as much as their younger counterparts derives from lower papillary urea concentration. In aging brain, UT-B1 abundance was increased twofold together with a fourfold increase in aquaporin-4 abundance. Dehydration did not alter the abundance of these transporters.

Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or V2receptor mRNA expression. Normalization of urine flow rate by 1-desamino-8-d-arginine vasopressin (dDAVP) was investigated in these animals. Long-term dDAVP infusion into 30-mo-old rats reduced urine flow rate and increased urine osmolality to levels comparable to those in control 10-mo-old rats. The maximal urine osmolality in aging rat kidney was, however, lower than that in adult kidney, despite supramaximal administration of dDAVP. This improvement involved increased inner medullary osmolality and urea sequestration. This may result from upregulation of UT-A1, the vasopressin-regulated urea transporter, in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. Expression of UT-A2, which contributes to medullary urea recycling, was greatly increased. Regulation of IMCD aquaporin (AQP)-2 (AQP2) expression by dDAVP differed between adult and senescent rats: the low AQP2 abundance in senescent rats was normalized by dDAVP infusion, which also improved targeting of the channel; in adult rats, AQP2 expression was unaltered, suggesting that IMCD AQP2 expression is not regulated by dDAVP directly. Increased AQP3 expression in senescent rats may also be involved in improved urine-concentrating capacity owing to higher basolateral water and urea reabsorption capacity.

The effects of food restriction on liver glucagon and vasopressin V1a receptors, on AGE accumulation and on gene expression were investigated in 10- and 30-month-old WAG/Rij female rats fed ad libitum or chronically food-restricted by 30%. The age-related increase in glucagon and vasopressin V1a receptor density, as well as the rise in glucagon-induced cAMP generation was prevented by the restriction. AGE accumulation, characteristic of the aging process, was normalized in food-restricted animals. Gene expression determined with rat Atlas cDNA Expression Arrays containing 1176 cDNA indicates that a few genes exhibited a greater than twofold change in mRNA ratios with age. Most down-regulated genes were related to oxidative metabolism of lipids, and most of the up-regulated genes were concerned with the cell cycle and transcription factors. Chronic food restriction partially prevents these changes in gene expression and induces up- and down-regulation of several mRNAs which are not modified with age in ad libitum fed rats.

Glucose tolerance is reduced with age. The relationship between this change in glucose homeostasis and signaling of glucagon and vasopressin V1a receptors was investigated in hepatocytes isolated from 10- and 30-month-old female WAG/Rij rats. Binding capacity of hepatocytes for 125I glucagon and 3H vasopressin increased 2- and 1.8-fold, respectively, between 10 and 30 months. Intracellular cAMP accumulation induced by glucagon was 40% greater in hepatocytes of aging rats than of adults, although EC50 were similar in the two groups. Conversely, phosphodiesterases activity and nucleotides leakage out of the cells were unchanged with age. The rise in intracellular calcium consecutive to the stimulation of V1a receptor was comparable in adult and senescent animals. Finally, glucose release by hepatocyte suspensions was greater in senescent than in adult animals in absence as in presence of glucagon. These experiments suggest that increase in glucagon receptor expression and cAMP generation would contribute to the impaired glucose tolerance characteristic of the aging process.

This study was designed to evaluate the effects of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), on the reactivity and intracellular calcium ([Ca2+]i) mobilization induced by noradrenaline in the perfused tail artery from aged WAG/Rij rats. Global mean internal diameter was 350±15 microns and wall thickness 161±3 microns. The influence of the endothelium on these responses was also analysed. The intracellular dye fura-2 for [Ca2+]i measurements was used. Noradrenaline-induced vasoconstriction decreased progressively from 3 to 20 and 30 months. Removal of the endothelium attenuated vasoconstriction in 20 and 30 month-old rats (P

In female Wistar/Rij rats, 10 and 30 mo old, the micturition profiles in conscious animals, the contractile responses of the isolated urinary bladder, and the histology of the vesical tissue have been investigated. During cystomanometry, 60% of conscious senescent rats, but only 25% of young adult rats, showed spontaneous contractions during the bladder-filling phase. In aging rats, micturition pressure and duration of micturition were significantly higher by approximately 40-50%. In contrast, bladder capacity, bladder compliance, micturition volume, and residual volume were not modified with age. In vitro, the contractile responses of the bladder body to KCl, carbachol, arecoline, and alpha,beta-MeATP were similar in tissues from young adult and senescent rats. In contrast, maximum responses to noradrenaline, but not phenylephrine, were two times greater in the older rats. Isoprenaline exhibited the same potency in relaxing KCl-precontracted bladder body of 10- and 30-mo-old animals. Morphometric analysis showed a significant increase in the mean thickness of the muscularis layer with age, whereas the collagen density significantly decreased in the muscularis and in the lamina propria layers. The fact that the majority of senescent rats displayed bladder instability and increased response to alpha-adrenergic agonists suggests that this strain of rat seems a good model for the aged human. However, other characteristics of the aging human urinary tract (urinary frequency, decreased cystometric capacity, and decreased detrusor contractility associated with fibrosis) are not present.

The structural requirements for internalization and signalling of the vasopressin V1a receptor were investigated in stably transfected HEK-293 cells. Removal of the 51 C-terminal amino acids did not affect vasopressin binding, calcium signalling, heterologous desensitization or internalization of the receptor. Deletion of 14 additional amino acids reduced vasopressin-dependent calcium increase and impaired receptor internalization. Substitution of cysteines 371-372 did not affect intracellular signalling, but decreased endocytosis by 26%. Substitution of the 361-362 leucine by alanine residues reduced by 56% V1a receptor sequestration without affecting calcium signalling. These results indicate that di-cysteine and mostly di-leucine motifs present in the C-terminal region of the V1a receptor are involved in its internalization.

Aging is associated with cardiac hypertrophy and arterial stiffening possibly associated with accumulation of advanced glycation end products (AGEs). We evaluated the effect of aminoguanidine, an inhibitor of AGE production, on end-stage alterations of renal and cardiovascular systems. Normotensive WAG/Rij rats were treated from 24 to 30 mo with aminoguanidine and compared with a control group. Aminoguanidine did not modify body and kidney weights but prevented the age-related cardiac hypertrophy (heart weight: 1276 ± 28 mg and 1896 ± 87 mg in 24- and 30-mo-old control animals and 1267 ± 60 mg in 30-mo-old treated rats, P < 0.01). The increase in mesangial surface in aging rats was reduced by 30% by aminoguanidine. Collagen content of the arterial wall increased between 24 and 30 mo whereas elastin content, media thickness, and smooth muscle cell number remained unchanged. Aminoguanidine did not affect these parameters; however, the age-related increase in aortic impedance (12.4 ± 1.4 and 18.2 ± 1.9 10 3 ⋅dyne⋅sec⋅cm −5 in control 24- and 30-mo-old rats, P < 0.01) and the decrease in carotid distensibility (0.79 ± 0.11 and 0.34 ± 0. 07 mm Hg −1 in control 24- and 30-mo-old rats, P < 0.01) were prevented by aminoguanidine. The prevention of arterial stiffening and cardiac hypertrophy in the absence of changes in collagen and elastin content suggests that the effect of aminoguanidine is related to a decrease in the AGE-induced cross-linking of the extracellular matrix.

The role of protein kinase C activation and carboxyl-terminal region in rapid desensitization of the vasopressin V1a receptor was investigated in Xenopus oocytes. Preincubation of the oocytes with vasopressin or with the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), or direct injection of active protein kinase C, all blunted the calcium response of the V1a receptor. Truncation of the 51 terminal amino acids (S374STOP) modified neither the intracellular calcium response to vasopressin nor its desensitization by vasopressin or OAG. These data suggest that desensitization of the V1a receptor is mediated by PKC activation and that its carboxyl-terminal domain is not required for signal transduction and rapid desensitization.

The activity of the renin-angiotensin system as well as the ability of the kidney to retain sodium following salt restriction are reduced with age. The relationship between these age-related changes in renal function and the renin gene expression was presently investigated. The concentrations of renin and its mRNA were measured in kidney of 10- and 30-month-old control female WAG Rij rats and of animals which were salt restricted for 4 days. In the senescent rats, the kidney renin concentration, like the plasma concentration of angiotensin II, was half that in adult rats. The intrarenal content of renin mRNA did not differ between 10- and 30-month-old animals, suggesting that the transcriptional rate of the renin gene is unchanged with age. During the early phase of adaptation to sodium depletion, the systemic angiotensin II concentration was not modified in either age groups. Four-days salt restriction did not significantly change the renal storage of renin. In contrast, this short term salt restriction induced a 2.3-fold increase in the renin mRNA in adult kidney, and a 1.9-fold increase in the senescent kidney. These data suggest that the age-related decrease in renal concentration of renin is linked to a modification in the rate of translation of renin mRNA, or to an alteration in the protein maturation. The difference in adaptation to the early phase of salt restriction with age should not be linked to changes in renin gene transcription, but more likely to a change in the tissue response to the local renin-angiotensin system.

Albumin glycation was investigated in old rats to elucidate the link between the preferential excretion of glycated albumin and age-related microalbuminuria. Postprandial blood glucose and the glycated albumin in the serum and urine of 3-, 10- and 30-month-old Wistar rats and in streptozotocin diabetic rats were determined. Blood glucose increased from 1.46 +/- 0.046 g l-1 in 3-month-old rats to 2.08 +/- 0.06 (10 months) and 1.75 +/- 0.23 (30 months) (P0.05). Albumin glycation level in the serum increased from 0.79 +/- 0.07 nmol HCHO/nmol albumin (3 months) to 1.41 +/- 0.14 (10 months) and 1.73 +/- 0.21 (30 months) (P0.05); urinary level increased from 1.63 +/- 0.39 nmol HCHO/nmol albumin (3 months) to 2.92 +/- 0.57 (10 months) and 2.39 +/- 0.36 (30 months) (P0.01). The percent glycated albumin in serum rose from 3.33 +/- 0.64 to 6.81 +/- 0.63 and 6.99 +/- 1.79% of total albumin (P0.05), whereas the urine percentage decreased from 12.81 +/- 3.97 to 12.64 +/- 2.87 and 2.63 +/- 0.97% (P0.05) in 3-, 10- and 30-month-old rats, respectively. Editing decreased with aging from 4.28 +/- 0.83 (3 months) to 1.84 +/- 0.32 (10 months) and 0.52 +/- 0.14 (30 months) (P0.01). Editing in microproteinuric diabetic rats was lower (0.95 +/- 0.08) than in 3-month-old control rats (P0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A three-day training programme on sleep in hospitals was created in 2008 on the initiative of the national association for the continuing training of hospital staff, in collaboration with the French ministry of health. 448 nurses have been trained thanks to a participative programme integrating new, interactive pedagogical tools.

Unintentional weight loss and Undernutrition are major problems among older people living in Long-Term Care Facilities (LTCF). Undernutrition manifests in LTCF particularly as weight loss and low Body Mass Index (BMI) and is associated with increased morbidity and mortality as well as with functional decline. There are many factors associated with poor nutritional status and affecting protein-energy intake and/or energy expenditure. These include age of 85 years or older, low nutrient intake, loss of ability to eat independently, swallowing and chewing difficulties, becoming bed-ridden, pressure ulcers, history of hip fracture, dementia, depressive symptoms and suffering from two or more chronic illnesses. Nutritional evaluation is an essential part of the Comprehensive Geriatric Assessment (CGA). This evaluation ranges from methods such as BMI to several validated tools such as Mini-Nutritional Assessment (MNA). After diagnosis, the management of undernutrition in LTCF requires a multidisciplinary approach which may involve dietary and environmental improvements and managing multiple co-morbidities, while avoiding polypharmacy as far as possible. Finally, the need for supplementation or artificial (tube) feeding may be considered taking into account the CGA and individual needs. This document presents a succinct review and recommendations of evaluation and treatment of undernutrition.

The loss of neurons is viewed as one of several causes of the deterioration of neural function during ageing. However, the existing experimental evidence for an age-related decrease in the neuronal number may be misinterpreted due to the way the cells are counted and to the interference of unsuspected degenerative pathology of the animals studied. To reinvestigate this question we have quantified an easily identifiable population of neurons, the cerebellar Purkinje cells, in very old but healthy rats. The number of Purkinje cells in the cerebellum was assessed in two populations of rats: control (10 months) and old (42 months) rats from the Wistar/Louvain strain. In both groups, paraffin-embedded brains were cut serially in the sagittal plane. Purkinje cells were counted every 15 or 22 sections under the light microscope at a magnification of 1250×. The raw value of cell counts were corrected according to the method of Hendry (21) in order to avoid the overestimation due to splitting of the nucleus during sectioning. The latero-lateral extent of the cerebellar cortex, obtained by multiplying the thickness of the section by the number of sections in which Purkinje cells were counted, was not statistically different (mean±standard deviation): 12.8±1.16 mm (n=6) for the control rats and 12.0±1.02 mm for the old animals (n=8) (Student's t-test, p=0.18). The corrected number of the Purkinje cells (mean±standard deviation) was 330, 350±35,448 cells (n=6) for the control animals and 299,019±50,223 (n=8) cells for the old rats. The 9.5% reduction observed in aged animals was not statistically significant (p=0.22). In conclusion, our studies indicate that, in the cerebellum of the Wistar/Louvain rat, if anything, the effect of ageing upon the Purkinje cell population is very mild.

Renal failure in the elderly is currently underestimated and presents a real challenge for the public health system. Kidney function must be routinely assessed by creatinine clearance, estimated with either the Cockcroft and Gault formula or the simplified MDRD formula, which appears especially appropriate for the elderly. Normal kidney aging is related to tissue and functional changes that make older patients very vulnerable to environmental modifications. Numerous factors can accelerate the impairment of rental function during aging. Some of them cannot be modified: sex, genome, and initial kidney disease. Most of them can be managed or treated: hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, proteinuria, and the presence of oxidation and glycation products. Chronic renal failure in the elderly must be managed early with strict treatment targets to avoid the development of end-stage renal disease. Inhibitors of the renin-angiotensin-aldosterone system play an essential role in optimizing nephroprotection: control of hypertension, diabetes complications, and proteinuria. They should be prescribed very carefully in older patients. Age is not a prerequisite for consultations with nephrologists, which should take place early so that nephroprotection can still be useful.

Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin (AVP)/V2receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 (AQP2) water channel in the inner medullary collecting duct (IMCD). We showed previously that dDAVP administration could partially correct this defect. Since AQP2 can also be regulated by AVP-independent pathways in water deprivation (WD), we investigated AQP2 and phosphorylated AQP2 (p-AQP2) regulation in thirsted adult (10 mo old) and senescent (30 mo old) female WAG/Rij rats. Following 2-day WD, urine flow rate decreased and urine osmolality increased in both groups. However, in agreement with significantly lower cortico-papillary osmotic gradient with aging, urine osmolality remained lower in senescent animals. WD induced sixfold increase of plasma AVP in all animals which, interestingly, did not result in higher papillary cAMP level. Following WD, AQP2 and p-AQP2 expression increased hugely in 10- and 30-mo-old rats and their mistargeting in old animals was corrected. Moreover, the age-related difference in AQP2 regulation was abolished after WD. To further investigate the mechanism of AQP2 underexpression with aging, AQP2 mRNA was quantified by real-time RT-PCR. In the outer medulla, preservation of AQP2 protein expression was achieved through increased AQP2 mRNA level in senescent rats. In the IMCD, no change in AQP2 mRNA was detected with aging but AQP2 protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of AQP2 with aging, which is abolished by WD.

The prevalence of sleep disorders increases with age and reaches 20 to 40% of those older than 60 years. We set up a health education program to help the elderly to improve their sleep. It includes a preliminary 9-day evaluation with a sleep diary and wrist actigraph, a day of group cognitive behavioral therapy, and a follow-up assessment, again with sleep diary and actigraph.Of the 26 study participants (9 men and 17 women, mean age: 68+/-1 years), 14 had insomnia with night awakenings of 1 hour or longer or a sleep latency of 30 minutes or longer or both (group 1). The other 12 (group 2) also complained of insufficient sleep.In the weeks following cognitive behavioral therapy, group 1 improved their total sleep time by an average of 24 to 33 minutes, with reduced night-time awakenings and sleep latency and no change in their time spent in bed. Those in group 2 also increased their total sleep time by 18 to 47 minutes, by spending more time in bed and maintaining a sleep efficiency close to 88%.This study showed that cognitive behavioral therapy coupled with individual sleep evaluation improves sleep duration in elderly people who complain of insufficient sleep. These beneficial effects were accompanied by positive assessments of both subjective sleep quality and morning energy.

Insomnia affects 20% of the adult population in western countries and its prevalence increases with age. There is a controversy regarding the origin of sleep disorders in elderly. Are they only due to a senile process of sleep functioning or due to other associated comorbidities? Considering the objective assessment of sleep in elderly (by polysomnography), it has been shown an increasing sleep latency, decreasing total sleep time and sleep efficiency, a lower percentage of slow wave sleep. The circadian clock is also modified by age with phase advance and a decreased amplitude of the circadian rhythms. The most relevant comorbidities found in older people are: sleep apneas, restless leg syndrome, psychiatric disorders (anxiety and depression) and the use of drugs.

Gene expression in aging kidney and pituitary was determined by subtractive hybridization, DNA micro arrays and RT-PCR. Kidneys and pituitary were removed from 10- and 30-month-old female WAG/Rij rats, which were free from chronic progressive nephrosis and had a low incidence of pituitary tumors with age. From 350 cDNA fragments isolated by subtractive hybridization, just one showed a more than twofold change in expression between 10 and 30 months. The use of a specific micro array with 4050 rodent genes also failed to detect downregulation lower than 0.5 or upregulation larger than 2.0 in aging rat kidney. Similarly,mRNA content for vasopressin V2 and V1 receptors, aquaporin 2 and 3, and adenylyl cyclase type VI was not significantly modified with age as determined by RT-PCR. In contrast,microarray analysis of pituitary mRNA expression showed upregulation of 11 genes with ratios equal to or greater than 2.0 and downregulation of 6 genes with ratios equal to or less than 0.5. Two cDNA sequences of unknown genes from the kidney subtractive library were part of the age-related up- and downregulated genes of the pituitary. Other genes were mainly related to cell differentiation, control of homeostasis, cellular signaling, endoplasmic reticulum trafficking and metabolism. These data indicated that mRNA expression is barely modified in aging kidney free from chronic progressive nephrosis, at least in the 0.5–2.0 range, in contrast to pituitary. They also suggest that the downregulation of proteins reported in aging kidneys free from gross disease is related to post-transcriptional changes.

Our objective was to study age-related changes in adrenergic contractility and gene expression profile in the rat urinary bladder. Young (3-month old), adult (10-month old) and senescent (30-month old) male WAG/Rij rats were used. Gene expression profile in the rat urinary bladder was defined using AtlasTM microarray technology. In vitro contractile responses induced by KCl, phenylephrine (PHE) and norepinephrine (NE) were compared in isolated urinary bladders dissected from young, adult and senescent rats. Among a total of 1176 genes present on the arrays, 15 genes showed an increase in expression and 10 genes a decrease with age. Four genes related to nerve growth factor were upregulated whereas NOS type III was downregulated in aging rats. Intrinsic contractility of isolated rat urinary bladders was not changed between adult and aging rats as judged by the response curves to KCl. In contrast, an age-related increase in the maximal contractile responses to NE, but not PHE, was noticed (13 ± 1, 48 ± 2% and 59 ± 2% at 3, 10 and 30 months, respectively). The α1D-adrenoceptor antagonist BMY7378 antagonized NE-induced contractions with low potency in both groups suggesting the involvement of the α1A-adrenoceptor subtype. This was confirmed by microarray, which demonstrated mRNA expression for the α1A -adrenoceptor subtype only. These results suggest that aging of the urinary bladder is associated with an increase in the maximal contractile response to NE which could be due to NO shortage resulting from downregulation of urothelial NOS III.

Aging is accompanied by a gradual deterioration of cell functions. Mitochondrial dysfunction and accumulation of protein damage have been proposed to contribute to this process. The present study was carried out to examine the effects of aging in mitochondrial matrix isolated from rat liver. The activity of Lon protease, an enzyme implicated in the degradation of abnormal matrix proteins, was measured and the accumulation of oxidation and glycoxidation (Nepsilon-carboxymethyllysine, CML) products was monitored using immunochemical assays. The function of isolated mitochondria was assessed by measuring respiratory chain activity. Mitochondria from aged (27 months) rats exhibited the same rate of oxygen consumption as those from adult (10 months) rats without any change in coupling efficiency. At the same time, the ATP-stimulated Lon protease activity, measured as fluorescent peptides released, markedly decreased from 10-month-old rats (1.15 +/- 0.15 FU x micro g protein-1 x h-1) to 27-month-old-rats (0.59 +/- 0.08 FU x micro g protein-1 x h-1). In parallel with this decrease in activity, oxidized proteins accumulated in the matrix upon aging while the CML-modified protein content assessed by ELISA significantly increased by 52% from 10 months (11.71 +/- 0.61 pmol CML x micro g protein-1) to 27 months (17.81 +/- 1.83 pmol CML x micro g protein-1). These results indicate that the accumulation of deleterious oxidized and carboxymethylated proteins in the matrix concomitant with loss of the Lon protease activity may affect the ability of aging mitochondria to respond to additional stress.

With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (−34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (−14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total−(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (−20%), leading to a fall in the elastic modulus/wall stress ratio (−27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 ± 0.3 ml/24 h and 2,511 ± 54 mosmol/kgH2O in adult rats and 12.8 ± 0.8 ml/24 h and 1,042 ± 44 mosmol/kgH2O in senescent animals. Vasopressin V2receptor mRNA did not significantly differ between 10 and 30 mo, and [3H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.

Aging is frequently associated with impaired ability to retain water. This is accounted for by changes in thirst and altered kidney concentrating ability. The mechanisms involved in this process hasve been studied in many different models. In humans, the thirst threshold appears to increase with age which results in impaired water homeostasis (see Vellas et al., 1998 for a review). In addition, a defect in renal water reabsorption has been described. In rodents, in particular, aging is characterized by polyuria and decreased urinary osmolality (Corman & Michel, 1987). Because water reabsorption in kidney is regulated by vasopressin (AVP), these changes can be due to impaired AVP secretion or to inappropriate kidney response to AVP.

The secretion of cerebrospinal fluid by the epithelial cells of choroid plexus is regulated by membrane receptors coupled to adenylyl cyclases or to phospholipase C. These intracellular signalling pathways as their interactions were investigated in a sheep choroid plexus cell line. Endothelin-1, bradykinin and serotonin induced a transient dose-dependent increase in intracellular calcium. EC 50 were 10 −8 M for endothelin-1, 10 −8 M for bradykinin and 10 −6 M for serotonin. Maximal increase in intracellular calcium was comparable for bradykinin and serotonin, but was 3 to 5 fold larger for endothelin-1. Successive stimulations with endothelin-1, serotonin or bradykinin elicited calcium increases similar to single stimulations reflecting absence of heterologous desensitization between these receptors. Forskolin-induced cAMP accumulation was potentiated by bradykinin, but not by serotonin and endothelin-1. This potentiation resulted from an increase in cAMP production rather than to an inhibition of cAMP hydrolysis. These data suggest that serotonin, endothelin-1 and bradykinin each use specific signalling pathways in the sheep choroid plexus cells.

Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transfected with the V1a and V2 vasopressin receptors. Cell lines expressing V1a, V2, or both V1a and V2 receptors, were established and characterized. Stimulation of V2 receptors by vasopressin induced a dose-dependent increase in cAMP accumulation, whereas stimulation of V1a receptor resulted in an increase in intracellular calcium without any change in basal cAMP. The simultaneous stimulation of V2 and V1a receptors by vasopressin elicited an intracellular cAMP accumulation which was twice that induced by stimulation of V2 receptor alone with deamino-[D-Arg8]vasopressin. This potentiation between V1a and V2 receptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleimide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying that an alteration in cAMP hydrolysis was not involved. Vasopressin, as well as PMA, had no effect on the forskolin-induced cAMP accumulation, suggesting that PKC did not directly stimulate the cyclase activity. On the other hand, vasopressin, like PMA, potentiated the cAMP accumulation induced by cholera toxin, an activator of Gαs protein. These results suggest that, in CHO cells, vasopressin V1a receptor potentiates the cAMP accumulation induced by the V2 receptor through a PKC-dependent increase in the coupling between Gs protein and adenylyl cyclase.

The V2 vasopressin and the AT1A angiotensin II receptors are respectively coupled to the adenylyl cyclase and the phosphoinositide pathways. The cross-talk between these two receptors and their transduction pathways were investigated in CHO cells transfected with cDNA of both AT1A and V2 receptors. In these cells, angiotensin II induced an increase in intracellular calcium, and vasopressin a rise in intracellular cAMP accumulation. The simultaneous addition of angiotensin II and vasopressin potentiated the production of cAMP by the V2 receptor. This potentiation was dose-dependent and, at a concentration of 10(-7) M angiotensin II, the accumulation of cAMP was 4-fold greater than that induced by 10(-7) M vasopressin alone. Such cross-talk occurred in the presence and absence of cyclic nucleotide phosphodiesterase inhibitors, indicating that inhibition of phosphodiesterase activity was not the principal cause of potentiation. This was confirmed by the absence of calcium-inhibitable isoforms of phosphodiesterases in CHO cells. The addition of angiotensin II to forskolin, which stimulates the adenylyl cyclase, did not modify the production of cAMP. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), partially mimicked, and staurosporine, an inhibitor of PKC, partially inhibited the effect of angiotensin II on vasopressin. Chelation of intracellular calcium with BAPTA-AM markedly reduced the potentiation of V2 receptor by angiotensin II. However, increase in intracellular calcium with thapsigargin did not modify the cAMP accumulation induced by vasopressin. It was concluded that, in CHO cells, activation of the AT1A receptor by angiotensin II potentiates the V2 receptor through activation of protein kinase C in the presence of intracellular calcium at a step located between the receptor and the adenylyl cyclase.

International audience; The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase.

The gender differences in the age-related changes of glomerular structures were determined in 10- and 30-month-old rats. In adult animals, glomerular volume, urinary space, capillary lumen area and mesangial domains of deep and superficial nephrons were larger in males than in females. Glomerular hypertrophy was evidenced with age in both males and females. This hypertrophy was greater in female (+70%) than in male (+20%) rats. Age-related hypertrophy concerned equally the urinary space and the glomerular tuft. The mesangial domain, however, increased more markedly than glomerular volume (+400%). As a result, the ratio of mesangial domain to glomerular section area was more than doubled between 10 and 30 months. In females, the age-related renal hypertrophy was associated with a constant total capillary lumen area in cortical nephrons. In contrast, the total capillary lumen area of male rats was reduced by 20% in superficial glomeruli and by 36% in deep glomeruli between 10 and 30 months. These morphological changes are in good agreement with the maintained glomerular filtration rate reported in old female rats and the decrease in renal blood flow and filtration rate reported in male rats. They suggest that the aging process does not similarly affect the vascular system of the kidney of male and female rats, although their mean blood pressure was comparable.

1. Age-related changes in noradrenergic neurotransmission in the tail arteries of three rat strains: outbred Wistar (WI/Ico), inbred Wistar (WAG/Rij) and inbred Fischer (F344) have been compared in the present study. 2. The arterial noradrenaline content varied from 5 to 10 ng mg-1 wet weight amongst young (3 to 6-month old) representatives of each strain, but did not change with age. As protein content increased in senescent rats (24-month old) by 30-40%, arterial tissue growth would not appear to receive a concomitant increase in sympathetic growth leading to relative, age-related, structural sympathectomy in all strains. 3. The vasoconstrictor response to transmural electrical stimulation was diminished in adult and senescent rats of all strains. 4. As far as could be judged from the increase in noradrenaline release following perfusion with the alpha-adrenoceptor antagonist, phentolamine (1 microM), the presynaptic alpha 2-adrenoceptor-mediated inhibition of noradrenaline release was intact in old representatives of all strains. 5. With blockade of the two main systems which control noradrenaline release in the rat tail artery, viz, neuronal reuptake with cocaine (4 microM) and presynaptic alpha 2-adrenoceptors with phentolamine (1 microM), stimulation-evoked release of noradrenaline was similar at all ages and in all strains. This suggests that in the rat tail artery the basic mechanism of neuronal release of noradrenaline is not functionally modified by aging. 6 We conclude that as sympathetic nerve terminals are apparently intact in all three strains of senescent rats used, the age-associated deficit of alpha-adrenergic control of vascular function is postsynaptic in nature.

Age-related changes in systemic arterial blood pressure, basal cerebral blood flow (CBF), and CBF regulatory capacity were investigated in awake 6-, 12-, 24-, and 30-mo-old male Wistar (WAG/Rij) rats, one-half of which received the angiotensin I-converting enzyme inhibitor (ACEI) perindopril from 6 mo onward. There was no age-dependent change in mean arterial blood pressure, basal CBF, or cerebrovascular reactivity to hypercapnia, but the lower limit of CBF autoregulation rose from 70 mmHg at 6 and 12 mo to 90 mmHg in 24- and 30-mo-old animals. ACEI lowered mean arterial blood pressure but had no effect on basal CBF or on cerebrovascular reactivity to hypercapnia. ACEI shifted the lower limit of CBF autoregulation to a 20-mmHg-lower level in 12- and 24-mo animals but not in rats treated for 2 yr, i.e., from the ages of 6 to 30 mo. In conclusion, the main age-related change in CBF regulation was an increase in the lower limit of CBF autoregulation to a higher blood pressure level. Treatment with ACEI partially restored the lower limit of CBF autoregulation.

The age-related changes in the structure and the function of the kidney and the effect of chronic inhibition of angiotensin-converting enzyme (ACE) activity on these alterations were assessed in senescent, genetically hypertensive rats. Mean blood pressure was unchanged between 6 and 21 months, being 136 +/- 10 and 135 +/- 21 mm Hg, respectively. Hypertrophy of the glomeruli with a high incidence of glomerulosclerosis was reported in the 21-month-old animals. Renal blood flow, glomerular filtration rate, and filtration fraction were reduced between 6 and 21 months, whereas albuminuria and cGMP excretion were markedly enhanced with aging. Chronic ACE inhibition by administration of 0.3 mg/kg/day trandolapril from 18-21 months increased the life expectancy of the animals without affecting their mean blood pressure. The incidence of glomerular lesions and the excretion of enzymes that reflected the integrity of tubular and glomerular cells were not altered by ACE inhibition. On the other hand, the filtration fraction was restored in the 21-month-old treated animals, and the age-related albuminuria and rise in cGMP excretion were prevented by ACE inhibition. These results indicated that ACE inhibitor administered at the end of the life of senescent hypertensive rats was able to prevent some of the age-related changes in kidney function when glomerulosclerosis was already present.

Food restriction or chronic converting enzyme inhibition (CEI) both limit age-related glomerulosclerosis and the associated proteinuria which occurs spontaneously in rats with renal mass ablation. Since hyperfiltration consecutive to the decreased number of nephrons may be damaging to the kidney, we investigated how fasting and CEI compare in lowering glomerular filtration rate in partially nephrectomized rats. Male Wistar rats were subjected to 3/4 nephrectomy and chronically catheterized. A week after surgery, the animals were separated into two groups, one control and one treated with the converting enzyme inhibitor perindopril (1 mg/kg/24 h) for ten days. In the control untreated 3/4 nephrectomized rats, successive measurements of kidney function in the same animal showed that renal blood flow and glomerular filtration were 30 to 50% higher in fed than in fasted animals. In the group treated with perindopril, there was no longer any such difference in the renal blood flow and filtration rate. These results indicate that, by blunting postprandial hyperfiltration, chronic converting enzyme inhibition is as effective as food restriction in reducing the load delivered to the kidney.

The effects of converting enzyme inhibition on the cardiac mass, isomyosins polymorphism, and collagen network in the left ventricle have been studied in renovascular, hypertensive, spontaneously hypertensive, and normotensive rats. The isoenzyme profile of left ventricular myosins was used as an indirect marker of the intrinsic property of contractility, whereas the collagen network, measured by a morphometric method, represented an indirect structural marker of the arrhythmogenic risk. One-clip, two-kidney renovascular hypertension was associated with cardiac hypertrophy, a shift in the isomyosin profile, and accumulation of collagen within the left ventricular myocardium. In this renin-angiotensin-dependent model, one month of treatment with converting enzyme inhibitor normalized blood pressure and consistently reversed cardiac hypertrophy and the isomyosin profile. Converting enzyme inhibitor treatment of 12-week-old spontaneously hypertensive rats for three months significantly decreased blood pressure but did not completely normalize it. The increase in cardiac mass observed in spontaneously hypertensive rats was not reversed by this short treatment. Nevertheless, the percentage of the V1 form of myosin increased slightly after treatment, and the collagen content of the left ventricle was considerably decreased. Converting enzyme inhibition did not decrease blood pressure in DOCA-salt hypertension, and no changes were observed in cardiac hypertrophy, isomyosin profile, or the collagen network. The cardiac hypertrophy that occurs with aging in normotensive rats was associated with a significant shift in isomyosin profile and a large accumulation of collagen. Thus, aging mimics several of the quantitative and qualitative changes in the left ventricular protein profile observed in hypertension. In young normotensive rats, converting enzyme inhibition significantly decreased blood pressure and left ventricular mass, increased the percentage of V1 isomyosin, and prevented the accumulation of collagen. In one-year-old normotensive rats, treatment for six months with converting enzyme inhibitor decreased blood pressure, decreased cardiac mass, and prevented the accumulation of collagen; the isomyosin profile was not modified. Converting enzyme inhibition, by acting on cardiac afterload, can bring about quantitative and qualitative changes in the cardiac proteins of both hypertensive and normotensive rats.