Rats Of Various Ages Research Articles

Impact of aging on kidneys of male Wistar albino rats: the protective antiaging role of resveratrol

Because aging leads to multiple health problems associated with changes in the structure and functions of a different organ system, this study aimed to assess the effect of aging on the histology of renal tissue in rats of various ages and the possible protective role of resveratrol. In the present study, twenty-four male Wistar albino rats were separated into three groups of eight animals each, including rats adult aged (6 months), and old-aged (24 months old). The elderly resveratrol-treated group was administered 25 mg/kg/day of resveratrol diluted in distilled water orally via gastric tube. The treatment lasted three months. At the end of the experiment, blood was drawn for serum creatinine analysis, the animals were sacrificed, and the kidneys were removed and processed for histological investigation. The findings revealed variable changes in kidney tissue, including glomerulosclerosis, compensatory glomerular hypertrophy, tubulointerstitial fibrosis, thickened glomerular basement membrane, arterial sclerosis, tubular dilatation with cast formation, atrophy of the tubules, infiltration of inflammatory cells, a rise in the rate of apoptotic cells, and a decrease in the glomerular number. These histological changes were associated with increased serum creatinine levels and kidney malondialdehyde (MDA), a marker of lipid peroxidation. The use of RES (Resveratrol) improved the creatinine level with a decrease in the MDA and improved the histological changes of aged kidney. As a result, the progression of aging was accompanied by different histological variations that interfered with the physiological functioning of the kidney, predisposing older persons to renal illnesses. Utilizing RES as a prophylactic and/or therapeutic medicine for aging-related renal changes is also possible.

Age-related Changes in Humanin Expression in the Ovarian Tissue of Rat.

This study examined humanin expression in rat ovarian tissue, its cellular localization, and its correlation with rat age under physiological conditions. A total of 40 Sprague-Dawley rats of various ages (2, 12, 30, and 60 days old and 1 year old) were grouped by age. Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group. In addition, Western blotting and Real-time quantitative reverse transcription PCR (qRT-PCR) techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group. The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues. In addition, cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes, interstitial cells, granulosa cells and theca cells in all levels of follicles after the primary follicles, and in the corpus luteum. The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats (P>0.05), whereas the levels of humanin expression in the ovarian tissues of 30-day-old, 60-day-old, and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats (P<0.05). The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats (P<0.01), whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats. This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues. Moreover, the level of humanin expression was highest in the ovarian tissues of 12-day-old rats, and it subsequently decreased with age. The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging. The effect of humanin on ovarian function is worthy of further study in the future.

Corrigendum for: Sex Differences in Blood Pressure, Free Radicals and Plasma Cholesterol Fractions in Ren-2 Transgenic Rats of Various Ages.

List of changes: On the basis of author's request the publisher of Physiological Research decided to change the license of the article to CC BY license.

THE IMPORTANCE OF AGE-RELATED CHANGES IN INTERCALATED DISKS IN THE FUNCTIONING OF CARDIOMYOCYTES

The volume of the extracellular matrix rises along with the age increase. The presence of intercellular junctions and the exchange processes of electrical impulses and ion currents carried out via them is a critical component in the functioning of cardiomyocytes (both primary and secondary). The intercalated discs may engage in compensatory-adaptive responses resulting from age-related involutional processes, as evidenced by an increase in their quantity in the hearts of older rats. The structural integrity of the intercalated discs in young and middle-aged rats may be directly correlated with the highly functional capabilities of the heart muscle. It would be interesting to conduct a more in-depth study of the intercalated discs using immunohistochemical techniques and a comparative analysis of disc histological structure in rats of various ages by extrapolating the findings on the functional capabilities of cardiomyocytes.

Pulmonary ACE2 expression in neonatal and adult rats.

Children show a distinct presentation of COVID‐19, characterized by a lower incidence and mild phenotype, but the reason for this is still unknown. The angiotensin‐converting enzyme 2 (ACE2) functions as the primary cell entry receptor for Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and is thought to cause distinct clinical features between children and old people. The primary purpose of this study was to determine whether differences exist in the level of expression and distribution of ACE2 between neonatal and adult rat lungs. The lung tissues from rats of various ages were used to investigate the expression patterns of ACE2. Western blot, immunohistochemistry, and immunofluorescence were used to quantify or identify the localization of ACE2 in rat lungs. ACE2 was homogenously expressed in fewer alveolar type II (AT2) cells in the neonatal lung, with no polarization to the alveolar space and additional expression in pulmonary endothelium when compared to adult rat lungs. These findings suggest that the patterns of ACE2 distribution and cellular localization in rat lungs change with age.

Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts.

Aging represents a major risk for developing cardiac disease, including heart failure. The gradual deterioration of cell quality control with aging leads to cell death, a phenomenon associated with mitochondrial dysfunction in the heart. Apoptosis is an important quality control process and a necessary phenomenon for maintaining homeostasis and normal function of the heart. However, the mechanism of mitochondria-mediated apoptosis in aged hearts remains poorly understood. Here, we used male Fischer 344 rats of various ages, representing very young (1 month), young (4 months), middle-aged (12 months), and old (20 months) rats, to determine whether mitochondria-mediated apoptotic signals and apoptosis in the left ventricle of the heart are altered notably with aging. As the rats aged, the extramyocyte space and myocyte cross-sectional area in their left ventricle muscle increased, while the number of myocytes decreased. Additionally, mitochondrion-mediated apoptotic signals and apoptosis increased remarkably during aging. Therefore, our results demonstrate that aging promotes remarkable morphological changes and increases the degree of mitochondrion-mediated apoptosis in the left ventricle of rat hearts.

Propofol Improved Glucose Tolerance Associated with Increased FGF-21 and GLP-1 Production in Male Sprague-Dawley Rats.

Anesthetics, particularly volatile anesthetics, have been shown to impair glucose metabolism and cause hyperglycemia, closely linking them with mortality and morbidity as related to surgery. Beyond being an anesthetic used for general anesthesia and sedation, intravenous hypnotic propofol displays an effect on glucose metabolism. To extend the scope of propofol studies, its effects on glucose metabolism were evaluated in male Sprague-Dawley rats of various ages. Unlike chloral hydrate and isoflurane, propofol had little effect on basal glucose levels in rats at 2 months of age, although it did reduce chloral hydrate- and isoflurane-induced hyperglycemia. Propofol reduced postload glucose levels after either intraperitoneal or oral administration of glucose in both 7- and 12-month-old rats, but not those at 2 months of age. These improved effects regarding propofol on glucose metabolism were accompanied by an increase in insulin, fibroblast growth factor-21 (FGF-21), and glucagon-like peptide-1 (GLP-1) secretion. Additionally, an increase in hepatic FGF-21 expression, GLP-1 signaling, and FGF-21 signaling, along with a decrease in endoplasmic reticulum (ER) stress, were noted in propofol-treated rats at 7 months of age. Current findings imply that propofol may turn into insulin-sensitizing molecules during situations of existing insulin resistance, which involve FGF-21, GLP-1, and ER stress.

Effect of Age on Histological Changes of Urogenital Tract in Albino Rats

This study was conducted to investigate the histologic changes of kidney, urinary bladder, testis, seminal vesicle and prostate gland of rats of various ages (6,12 and 18 months old). Results illustrated variable changes of kidney represented by congestion of renal capillaries, acute tubular necrosis, shrinkage of glomerular tuft, degeneration in tubular epithelium of the 6,12 and 18 months old rats, the morphometric changes of the glomerular diameter decreases with advanced age. The lesions of urinary bladder characterized by hyperplasia of the epithelial lining, papillae into the lumen, hypertrophy of muscle fibers, desquamation of epithelium, cystitis in addition to thickening of the mucosa and hyalinization of muscle fibers of the 6,12 and 18 months old rats. The thickness of the bladder wall showed a significant changes increase at (P≤0.05) with age, while morphometric analysis did not show any age related changes in the bladder muscle thickness. In testis there were congestion of blood vessels, a spermia, degeneration of the spermatocytes and spermatozoa, thickening of interstitial and hyperplasia of leydig cells of the 6,12 and 18 months old rats. The wall thickness of Seminiferous tubule increases with age and basement membrane thickness and tubular diameter decreased with age. The seminal vesicle of the 6,12 and 18 months old rats revealed hyperplasia of glandular epithelium. Lesions of the prostate gland of 6,12 and 18 months old rats showed epithelial hyperplasia which extended as finger-like projections and presence of variable amounts of colloid substance.

Noninvasive Monitoring of Choroid-Retina Autofluorescence and Intravitreal Nanoparticle Disposition in Royal College of Surgeon Rats of Different Ages and Retinal Thinning.

Purpose: To determine the baseline choroid-retina fluorescence signal in Royal College of Surgeon (RCS) rats of various ages with different degrees of retinal degeneration and assess the persistence of intravitreal nanoparticles. Methods: In RCS rats of age 6, 12, and 20 weeks and Sprague Dawley (SD) rats of age 6 and 20 weeks, baseline eye tissue fluorescence and retinal thickness were recorded noninvasively using fluorophotometry and optical coherence tomography (OCT), respectively. Further, 20-nm carboxylate-modified fluorescent particles were injected intravitreally in the above groups of rats, and the depth-wise fluorescence signal was monitored over 7 days using fluorophotometry and confocal laser scanning ophthalmoscopy (cSLO). Additionally, 200 nm particles of the same material were injected intravitreally into about 7-week-old RCS rats and the fluorescence signal was monitored up to 35 days using fluorophotometry. Results: Reduction in retinal thickness and an increase in choroid-retina and lens baseline fluorescence was observed with increasing age of RCS and SD rats. The 20 nm particles persisted in the vitreous of animals from all age groups for at least 7 days postadministration, irrespective of the differences in retinal thickness. cSLO confirmed nanoparticle persistence in the eye. The fluorescence signal from 200 nm particles persisted for 35 days in the vitreous humor. Conclusions: Choroid-retina and lens autofluorescence monitored using fluorophotometry increase with age. Intravitreally injected nanoparticles can be monitored noninvasively in rats using fluorophotometry and cSLO imaging. Both 20 and 200 nm particles persist in the back of the eye tissues, for several days following intravitreal injection.

RESISTANCE OF ENAMEL IN SUPRA-OCCLUSION CONTACTS OF INDIVIDUAL TEETH IN RATS OF VARIOUS AGES

Introduction. Supra-occlusion is a position of a group of teeth or individual teeth, the cutting edge or chewing surface of which is located above the occlusal plane. This condition is characterized as primary traumatic occlusion, supra-contact or traumatic nodes, in which a number of structural and functional changes occur in the hard tissues of the teeth and periodontal tissue. Traumatic occlusion of teeth is often caused by occlusal intervention, such as high fillings or prostheses, parafunctional habits. In physiological conditions, the protection of teeth from chemical and mechanical interventions is provided by their structural and functional resistance. However, the influence of supra-occlusion on the resistance of tooth enamel, and especially in different age groups, has not yet been studied. Therefore, we consider this topic relevant. The objective of the work was to study the state of enamel resistance in supra-occlusal contacts of individual teeth in rats of various ages according to the enamel resistance test (ERT-test). Materials and methods. The study involved 36 white male laboratory rats aged 4 to 22 months and weighing 100 to 210 g. The animals were divided into two groups (control and experimental), each was divided into three subgroups (6 animals each) according to age categories: young, mature, old-aged. In the study group, the state of supra-occlusion was simulated by increasing the height of the lower right second molars via filling 1 mm in height, without preparation of hard tissues of the teeth. Previously, the animals were anesthetized intramuscularly with sodium thiopental solution. After removing the animals from the experiment on the 15th day by decapitation under general anesthesia with sodium thiopental, by intraperitoneal injection, the dental blocks were removed and the structural and functional state of the tooth enamel was determined by the ERT-test. Statistical processing of data was performed using the program AtteStat V.12.5 with the determination of the mean and its error (M ± m). The probable significance of the difference in the obtained data was determined by the Student's t-test (p ≤ 0.05). Study results. In the control group, ERT-test values decreased (enamel resistance increased accordingly) in rats, depending on age. In young rats, enamel resistance to acidic dissolution was the smallest, and in mature and old-aged rats it increased. However, the difference between the age groups was not statistically significant (p &gt; 0.05). A similar situation was registered in animals of the study group. However, statistically significant differences were observed only between young and old-aged rats (p = 0.025). In the control group, the acid resistance of enamel is higher compared to study group (p = 0.007). In young rats from the control group, enamel resistance to acids was 16.7% higher than in the study group (p = 0.025). In mature animals of the control group, the resistance of enamel to acid dissolution is 17.7% higher than in the study group (p = 0.046), and in old-aged – by 15.2% (p = 0.2). Conclusions. The resistance of enamel of teeth that are subjected to increased stress via supra-occlusal interactions is reduced in young, mature and old-aged rats in comparison with the control group. Reduced enamel resistance can be one of the risk factors in the occurrence of dental caries.

Изменения белой пульпы селезенки у потомства спленэктомированных крыс различных возрастных периодов после введения 1,2-диметилгидразина

Изменения белой пульпы селезенки у потомства спленэктомированных крыс различных возрастных периодов после введения 1,2-диметилгидразина

Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia.

SummaryObjectiveMalformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia (SBH) and examine whether this model develops spontaneous epileptic seizures.MethodsTo generate bilateral SBH in rats, we combined RNAi‐mediated knockdown of Dcx and in utero electroporation with a tripolar electrode configuration enabling simultaneous transfection of the two brain hemispheres. To determine whether bilateral SBH leads to epileptiform activity, rats of various ages were implanted for telemetric electrocorticographic recordings and histopathological examination was carried out at the end of the recording sessions.ResultsBy 2 months, rats with bilateral SBH showed nonconvulsive spontaneous seizures consisting of spike‐and‐wave discharges (SWDs) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands. SWDs occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also, SWDs were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of SWDs were found to be uncorrelated with the size of SBH, SWDs were initiated in some occasions from brain hemispheres comprising a larger SBH. Lastly, SWDs exhibited absence‐like pharmacological properties, being temporarily alleviated by ethosuximide administration.SignificanceThis novel model of bilateral SBH with spontaneous epilepsy may potentially provide valuable new insights into causality between cortical malformations and seizures, and help translational research aiming at designing novel treatment strategies for epilepsy.

ВІКОВІ ОСОБЛИВОСТІ ЖИРНОКИСЛОТНОГО СКЛАДУ ЛІПІДІВ СИРОВАТКИ КРОВІ ЩУРІВ З ОЖИРІННЯМ ПРИ ВПЛИВІ ЙОДУ

Вступ. У статті наведено нові дані про вікові особливості складу жирних кислот загального вмісту ліпідів сироватки крові білих щурів-самців з експериментальним аліментарним ожирінням у порівняльному ефекті внутрішньошлункового введення біологічно активного йоду в складі йодіс-концентрату і неорганічного йоду в складі йодомарину.&#x0D; Мета дослідження – вивчити порівняльний ефект біологічно активного йоду в складі йодіс-концентрату і неорганічного йоду в складі йодомарину на вміст жирних кислот загального вмісту ліпідів сироватки крові білих щурів-самців з експериментальним аліментарним ожирінням.&#x0D; Методи дослідження. Експериментальне аліментарне ожиріння моделювали протягом 45 днів на 48 білих щурах-самцях лінії Вістар різних вікових груп. Тварин поділили на 3 вікові групи по 16 щурів у кожній: 1-ша – віком 3 місяці; 2-га – 4 місяці; 3-тя – 6,5 місяця. У кожній віковій групі було 4 підгрупи: 1-ша – контрольна, тварини якої перебували на основному раціоні віварію; 2-га, 3-тя і 4-та – щури з експериментальним аліментарним ожирінням. Крім того, тваринам 3-ї групи внутрішньошлунково вводили біологічно активний йод у складі йодіс-концентрату, а щурам 4-ї групи – неорганічний йод у формі калію йодиду в складі йодомарину. Жирнокислотний склад визначали методом газорідинної хроматографії на газовому хроматографі HewlettPackardHP-6890 з полум’яно-іонізаційним детектором, обладнаному капілярною колонкою SP-2380, довжиною 100 м (Supelco).&#x0D; Результати й обговорення. У сироватці крові білих щурів усіх вікових груп з експериментальним аліментарним ожирінням спостерігали збільшення відносного вмісту насичених жирних кислот, головним чином за рахунок стеаринової кислоти, порівняно з інтактними тваринами. У щурів з експериментальним аліментарним ожирінням, які отримали йодомарин та йодіс-концентрат, результати були кращими відносно тварин 2-ї підгрупи.&#x0D; Висновок. Йод позитивно впливає на склад жирних кислот загального вмісту ліпідів сироватки крові білих щурів-самців з експериментальним аліментарним ожирінням.

Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging.

Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.

Effects of Extracellular Diadenosine Tetraphosphate on Action Potentials in the Atrial and Ventricular Myocardium of the Rat Heart during Early Postnatal Ontogenesis

Diadenosine tetraphosphate (AP4A) belongs to a wide group of naturally derived endogenous purine compounds that have recently been considered as new neurotransmitters in the autonomic nervous system. It has been shown that AP4A induces inhibitory effects and modulates adrenergic control in the heart of adult mammals. Nevertheless, the physiological significance of AP4A in early postnatal development, when sympathetic innervation remains yet immature, has not been investigated. The aim of the present study was to elucidate the effects of AP4A on the heart bioelectrical activity in early postnatal ontogenesis. Action potentials (AP) were recorded using the standard microelectrode technique in multicellular isolated right atrial (RA), left atrial (LA), and ventricle (RV) preparations from male Wistar rats at postnatal days 1, 14, and 21 and from 60-day animals that were considered as adults. The application of AP4A caused significant reduction of AP duration in atrial (RA and LA) preparations from rats of all ages. Also, AP4A caused significant AP shortening in RV preparations from rats of various ages; however, the effect was more pronounced in 21-day-old and adult rats. AP4A failed to alter automaticity of RA preparations from the rats at postnatal days 1, 14, and 21 and weakly decreased spontaneous rhythm in RA preparations from the adult rats. The effect of AP4A was partially abolished by P2-receptor blocker PPADS in LA preparations from both 21-dayold and adult rats, while it failed to suppress AP4A-caused AP shortening in preparations from 1- and 14-dayold animals. Thus, extracellular AP4A causes shortening of AP both in the atrial and ventricular myocardium in the rats of early postnatal ontogenesis and in adults. The effect of AP4A depends on age only for ventricular myocardium where it may be attributed with growing contribution of diadenosine polyphosphates to the control of myocardium inotropy.

Age-associated expression of erythropoietin and its receptor in rat spiral ganglion neurons and its association with neuronal apoptosis and hearing alterations.

The present study aimed to determine the expression of erythropoietin (EPO) and the EPO receptor (EPOR) in spiral ganglion neurons (SGNs) in the inner ear of rats of various ages, and the associated neuronal apoptosis and hearing alterations. A total of 15 healthy rats (n=30 ears), were divided into three groups: i) A nominated infant group at post-natal day (PND) 12–14, ii) an adult group at PND 60 and iii) a 3-year postnatal aged group. Auditory brainstem response (ABR) measurements were performed on all rats. EPO and EPOR expression in the inner ear was detected by immunohistochemistry. In situ terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed to detect the apoptosis of SGNs. The average hearing thresholds of the ABR (decibels above normal hearing level) were 5.625±4.955 in the infant, 15.000±8.498 in the adult and 23.500±13.134 in the aged groups. Hearing thresholds for aged and adult rats increased significantly compared with infant rats. However, the difference in latencies of peak I was not significant (P>0.05). EPO in SGNs was detected during different developmental periods without significant alterations, but were reduced compared with Corti's organ or the stria vascularis. EPOR expression increased significantly from infant to adult stage, and this increased expression was maintained in the aged group. An age-associated increase in the apoptosis of SGNs was detected in all three groups (P=0.0347). The potential neuroprotective effects of EPO in SGNs may not be revealed during the aging process under natural conditions, and may be associated with spontaneous neuronal apoptosis and consequently, hearing diminution. However, the age-associated increase in EPOR in SGNs may exert a role in neuroprotection when necessary, for example in presbycusis.

Histological structure of the mandibular condylar cartilage in rats of various age after 60-day intake of epichlorohydrin

Histological structure of the mandibular condylar cartilage in rats of various age after 60-day intake of epichlorohydrin

Alpha-Tocopherol Counteracts the Effect of Ethanol on Cortical Spreading Depression in Rats of Various Ages, With and Without Ethanol Abstinence.

We previously demonstrated that acute and chronic treatment with ethanol (EtOH), respectively, decelerated and accelerated the propagation of cortical spreading depression (CSD) in rats and that the antioxidant carotenoid astaxanthin counteracted these effects. Here, we investigated whether noncarotenoid antioxidants exert the same action by testing α-tocopherol in rats of various ages, with and without 5 to 10 days of EtOH abstinence. Male Wistar young adult (60 to 80 days old) and mature adult (150 to 180 days old) rats received per gavage acute (1 day) or chronic (21 days) treatment with 3 g/kg/d EtOH combined with acute (300 mg/kg) or chronic (85 mg/kg/d) treatment with α-tocopherol or vehicle-only treatment (olive oil and water for α-tocopherol and EtOH, respectively). CSD was recorded over 4 hours and the velocity of CSD propagation was calculated. On both ages, animals under chronic EtOH treatment were subjected to CSD recording immediately after EtOH treatment or after a 5- to 10-day period of EtOH abstinence. In both age groups, acute and chronic EtOH exposure decelerated and accelerated CSD, respectively, versus the corresponding control groups. Addition of α-tocopherol counteracted the effects of EtOH on CSD, returning CSD velocities to levels in control groups (p < 0.05). Chronic α-tocopherol (85 mg/kg/d) did not alter CSD. Our data reinforce the counteracting role of antioxidants on brain processes involved in the action of EtOH on CSD and suggest that this role is not a particular property of carotenoids; furthermore, this general feature of antioxidants is not substantially influenced by age or by 5 to 10 days of EtOH abstinence.

Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats.

Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

Donor Age and Cell Passage Affect Osteogenic Ability of Rat Bone Marrow Mesenchymal Stem Cells.

Tissue engineering allows the restoration of pathologically damaged tissues such as cartilage and bone using bio-scaffolds containing functionally active cells. Bone-marrow-derived mesenchymal stem cells (BMSCs) are a promising source of cells for tissue engineering due to their multilineage differentiation potential. However, proliferative and osteogenic abilities of BMSCs, and quantity of stem cells decreases in the bone marrow in aged population. We cultured BMSCs isolated from rats of various ages and evaluated their morphology, activity, and differentiation potential. Cultured BMSCs formed monolayer of fibroblast-like cells and maintained their characteristic morphology for 7-10 generations. Flow cytometry showed that aging of the cultured cell population correlated with the decrease in the expression of mesenchymal and hematopoietic surface markers, such as CD44, CD45, CD90, and CD29. We detected strong correlation between the age of BMSC donor and ALP activity in BMSC culture induced with low doses of dexamethasone and vitamin C. Cells from 2- and 6-week-old donor SD rats exhibited markedly increased ALP activity that coincided with increased bone content and strong positive staining of mineralized nodules. In contrast, BMSCs isolated from 10-month-old donors showed the lowest ALP activity, and decreased bone content and mineralized nodules formation. Our results demonstrate that the increase in donor age negatively affects proliferation and differentiation capacity of BMSCs in culture.