Aged Rats Research Articles

The Possible Effect of Platelet Rich Plasma on Liver and Small intestine in Adult and Aged Male Rats. A Histological and Immunohistochemical Study

Abstract Introduction There is a general modest decline in the function of different organs in the body with aging. In the small intestine, there may be alterations in the intestinal morphology, as well as a decline in the absorption of fatty acids and sugars. The aging process decreases regenerative ability which significantly delays the restoration of liver function. Platelet-rich plasma (PRP) has recently attracted interest in many medical fields. PRP might has benefit effect on aged male rats. Aim of the Work This study aims to investigate the structural changes that might occur during normal aging and the possible effect of PRP intraperitoneal injection on adult and aged male albino rats. Materias and Methods Forty-two male albino rats were classified according to age into adult group and old aged groups. Adult male rats (300 -350 g), their age range between 6-8 months. Aged male rats (570-660 g), their age range between 12-24 months. They were divided randomly into four groups: Group I (Control adult): Included 14 rats that further subdivided into 2 equal subgroups: subgroup IA: untreated rats and subgroup Ib: rats were injected by sterile saline intraperitoneally (0.5 mL/kg by intraperitoneal injection 3 times/week). Group II (Control Aged): Included 14 rat that further subdivided into 2 similar subgroups as group I, Group III (Adult treated): Included 7 rats that received intraperitoneal injection of PRP (0.5 mL/kg by intraperitoneal injection 3 times/week), Group IV (Aged treated): Included 7 rats that received intraperitoneal injection of PRP as group III. Animals were kept under observation and the treated groups received intraperitoneal injections for 21 days. At the end of the experiment, Liver and small intestine specimens were processed for histological and immunohistochemical examination. Morphometric and statistical analysis was also done. Results Group II showed decrease in height of intestinal villi with disruption of their epithelium surface, increase spacing between enterocytes and abundant mononuclear cellular infiltration. Changes in the liver comprised nuclear and cytoplasmic changes that included an increase in nuclei number in hepatocytes with droplets fat infiltration. Treated Groups showed decreasing mononuclear cellular infiltration with decreasing collagen fibres and congested blood vessels. Conclusion Aging process enhanced the vulnerability to injury and inflammation in both the liver and small intestine. PRP had ameliorating effects on these changes.

Effects of sacubitril-valsartan on aging-related cardiac dysfunction

Heart failure (HF) remains a huge medical burden worldwide, with aging representing a major risk factor. Here, we report the effects of sacubitril/valsartan, an approved drug for HF with reduced EF, in an experimental model of aging-related HF with preserved ejection fraction (HFpEF).Eighteen-month-old female Fisher 344 rats were treated for 12 weeks with sacubitril/valsartan (60 mg/kg/day) or with valsartan (30 mg/kg/day). Three-month-old rats were used as control.No differential action of sacubitril/valsartan versus valsartan alone, either positive or negative, was observed. The positive effects of both sacubitril/valsartan and valsartan on cardiac hypertrophy was evidenced by a significant reduction of wall thickness and myocyte cross-sectional area. Contrarily, myocardial fibrosis in aging heart was not reduced by any treatment. Doppler echocardiography and left ventricular catheterization evidenced diastolic dysfunction in untreated and treated old rats. In aging rats, both classical and non-classical renin-angiotensin-aldosterone system (RAAS) were modulated. In particular, with respect to untreated animals, both sacubitril/valsartan and valsartan showed a partial restoration of cardioprotective non-classical RAAS.In conclusion, this study evidenced the favorable effects, by both treatments, on age-related cardiac hypertrophy. The attenuation of cardiomyocyte size and hypertrophic response may be linked to a shift towards cardioprotective RAAS signaling. However, diastolic dysfunction and cardiac fibrosis persisted despite of treatment and were accompanied by myocardial inflammation, endothelial activation, and oxidative stress.

Noise Exposure Promotes Alzheimer's Disease-Like Lesions and DNA Damage.

This study aimed to explore the mechanism by which noise contributes to the development of Alzheimer's disease (AD)-like lesions. Male Wistar rats (24 months) were allocated into two groups (n = 6 per groups): a noise group exposed to 98 dB sound pressure-level white noise for 4 hours daily from 8:00 to 12:00 for 30 days, and a control group without noise exposure. The cognitive functions of the rats were assessed using new-object recognition and Morris water maze tests. Then, hippocampal tissues were collected, and the levels of amyloid β 1-42 (Aβ1-42), Aβ1-40, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) were measured using enzyme-linked immunosorbent assay (ELISA). Protein expression was evaluated through Western blot. Noise exposure significantly impaired cognitive and recognition abilities, increased the escape latency, and decreased the number of crossings through the platform quadrant intersection and the time spent in the target quadrant (P < 0.01). The new-object exploration and recognition index of the rats in the noise group markedly decreased (P < 0.01). ELISA results indicated increases in Aβ1-40 and Aβ1-42 levels and decreases in BDNF and TrkB levels in the rat hippocampus in the noise group (P < 0.01). Western blot analyses revealed that beta-site amyloid precursor protein (APP) cleaving enzyme 1, phosphorylated tau protein, gamma-H2A histone family, member X, checkpoint kinase 2, p53, and p21 were remarkably elevated in the noise group (P < 0.01). Chronic noise exposure can cause hippocampal genetic damage in aged rats, leading to cognitive disorders and the development of lesions similar to those observed in AD. Thus, noise is a potential risk factor for neurodegenerative disorders.

N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions. This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues. The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis. The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes. The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

A Comparative Study of the Temperature Coefficient Q10 in Hibernating Ground Squirrels Urocitellus undulatus and Cooled Rats of Different Ages

A Comparative Study of the Temperature Coefficient Q10 in Hibernating Ground Squirrels Urocitellus undulatus and Cooled Rats of Different Ages

ANK-1, ANK-2, ITL-2 Polyphenols in a Dexamethasone-Induced Rat Model of Type 2 Diabetes Mellitus Treatment

Background: Diabetes mellitus (DM) is a prevalent endocrine disorder that significantly increases the risk of cardiovascular complications due to the dysfunction of the coagulation and anticoagulation systems, exacerbated by metabolic imbalances. Despite advancements in understanding DM's pathophysiology, the precise alterations in the hemostatic system remain inadequately explored, posing challenges in diagnosis and treatment. This study investigated the effects of polyphenolic compounds isolated from Hexagalloy-lglucose (ANK-1), Hepta galloyl-glucose (ANK-2), and Isatis tinctoria L. (ITL-2) on biochemical and coagulation parameters in a dexamethasone-induced type 2 diabetes mellitus (T2DM) model in rats. Methods: T2DM was induced in 25 aged white outbred rats by administering dexamethasone (0.150 mg/kg) twice daily, with a control group receiving saline. Biochemical parameters, including glucose, total protein, ALT, AST, cholesterol, and triglycerides, were measured using a semi-automatic analyzer. Coagulation parameters such as prothrombin time (PT), activated partial thromboplastin time (APTT), plasma recalcification time (RP), and fibrinogen levels were assessed using a single-channel coagulometer. Platelet aggregation was recorded using an aggregometer, and clot degradation was measured spectrophotometrically. Results: Dexamethasone administration induced significant hyperglycemia and hypercoagulation, evidenced by reduced PT, APTT, and RP, alongside increased fibrinogen levels. The administration of ITL-2 normalized all biochemical parameters, while ANK-1 and ANK-2 normalized glucose, cholesterol, and triglycerides but not ALT and AST levels. ANK-1, ANK-2, and ITL-2 demonstrated significant antithrombotic effects, with ITL-2 showing the highest efficacy, reducing clot mass and enhancing clot degradation. Conclusion: Polyphenolic compounds, particularly ITL-2, exhibit potential as therapeutic agents for managing coagulation abnormalities and hyperglycemia in T2DM. These findings highlight the importance of further research into plant-derived substances as safer and effective alternatives in diabetes management.

Mechanism of tea polyphenols improving the sarcopenia in the aged type 2 diabetes model rats via mitochondrial quality control

To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC). A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10), the aged model group(aged, n=10) and the aging T2DM model group(n=35). The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ). After STZ injection for 2 weeks, fasting blood glucose(FBG) ≥ 16.7 mmol/L was defined as successful T2DM model. When the model was successfully induced, the 30 model rats were randomly divided into aged T2DM group(Mod), 300 mg/kg TP teatment group(TP) and 3 mg/kg rosiglitazone treatment group(RSG) according to FBG, with 10 rats in each group. Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks. Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment, which was higher than that of the control group, indicating that the aging T2DM model was successfully established. FBG was detected by the blood glucose meter, gastnemius muscle relative weights was calculated, the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM), the expression of mitochondrial biosynthesis-related proteins PGC-1α, mitochondrial dynamics-related proteins(OPA1, DRP1) and mitochondrial autophagy-related proteins(P62, LC3) in gastnemius muscle were detected by western blot. Compared with the control group, the level of FBG and the expression of P53 in the Mod group were increased(P&lt;0.01). The gastnemius muscle relative weights, the expression level of PGC-1α, OPA1 and the ratio of LC3II/LC3I were decreased(P&lt;0.01). The expression level of P62 and DRP1 were significantly increased(P&lt;0.01). The number of mitochondria decreased, the volume decreased and a large number of vacuolization, and there were no obvious autophagolysosomes and fission and fusion. After 8 weeks, compared with the Mod group, the number of mitochondria in the gastrocnemius of TP and RSG groups, vacuolization, fission and fusion were improved, and the autophagolysosomes was significantly increased. The expression levels of P53, DRP1 and P62, the level of FBG in the TP group were significantly decreased(P&lt;0.01, P&lt;0.05). The expression levels of OPA1 and PGC-1α, the ratios of LC3II/LC3I and gastnemius muscle relative weights were significantly increased(P&lt;0.05, P&lt;0.01). TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.

Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production. Disease, genetic impairment, or deconditioning can harm muscle mitochondria, affecting energy production. Endurance training enhances mitochondrial function but assumes mobility. Individuals with limited mobility lack effective treatments for mitochondrial dysfunction because of disease or aging. Mitochondrial transplantation replaces native mitochondria that have been damaged with viable, respiration-competent mitochondria. Here, we used a rodent model selectively bred for low-capacity running (LCR), which exhibits innate mitochondrial dysfunction in the hind limb muscles. Hence, the purpose of this study was to use a distinct breed of rats (i.e., LCR) that display hereditary skeletal muscle mitochondrial dysfunction to evaluate the consequences of mitochondrial transplantation. We hypothesized that the transplantation of mitochondria would effectively alleviate mitochondrial dysfunction in the hind limb muscles of rats when compared with placebo injections. In addition, we hypothesized that rats receiving the mitochondrial transplantation would experience an improvement in their functional capacity, as evaluated through incremental treadmill testing. Twelve aged LCR male rats (18 months old) were randomized into 2 groups (placebo or mitochondrial transplantation). One LCR rat of the same age and sex was used as the donor to isolate mitochondria from the hindlimb muscles. Isolated mitochondria were injected into both hindlimb muscles (quadriceps femoris, tibialis anterior (TA), and gastrocnemius complex) of a subset LCR (n = 6; LCR-M) rats. The remaining LCR (n = 5; LCR-P) subset received a placebo injection containing only the vehicle without the isolated mitochondria. Four weeks after mitochondrial transplantation, rodents were euthanized and hindlimb muscles harvested. The results indicated a significant (p < 0.05) increase in mitochondrial markers for glycolytic (plantaris and TA) and mixed (quadricep femoris) muscles, but not oxidative muscle (soleus). Moreover, we found significant (p < 0.05) epigenetic changes (i.e., hypomethylation) at the global and site-specific levels for a key mitochondrial regulator (transcription factor A mitochondrial) between the placebo and mitochondrial transplantation groups. To our knowledge, this is the first study to examine the efficacy of mitochondrial transplantation in a rodent model of aging with congenital skeletal muscle dysfunction.

Effect of Young Plasma Therapy on Cognition, Oxidative Stress, miRNA-134, BDNF, CREB, and SIRT-1 Expressions and Neuronal Survey in the Hippocampus of Aged Ovariectomized Rats with Alzheimer's.

Menopause may increase the risk of Alzheimer's disease (AD) dementia. This study aimed to use young plasma therapy (YPT) to improve dementia caused by AD in aged ovariectomized rats. Female Wistar rats were used in the following groups: (a) young (CY) (180-200 g, 2-3 months, n = 10) and (b) old groups (250-350 g, 22-24 months, n = 60). The old rats were randomly assigned to six sub-groups: (1) control, (2) sham, (3) ovariectomized group (OVX), (4) OVX + Alzheimer disease (OVX + AD), (5) OVX + AD+ 17β-Estradiol (OVX + AD + E), and (6) OVX + AD + young plasma (OVX + AD + YP). Cognitive behaviors were evaluated using NOR, MWM, and PAL tests. MiR-134a, SIRT-1, CREB, and BDNF expressions were measured using real-time PCR and western blot, respectively. Oxidative stress in hippocampal tissue was assayed using ELISA kits. OVX and AD caused significant cognitive impairment (p < 0.001), up-regulated miR-134a (p < 0.001), down-regulated SIRT-1, CREB, and BDNF protein expression (p < 0.001), and decreased antioxidant marker levels (p < 0.001) compared to the sham group. YPT significantly restored miR-134a (p < 0.001), SIRT-1 (p < 0.001), CREB (p < 0.001), and BDNF (p < 0.001) protein expression in OVX + AD rats. YPT, as much as or more than estrogen therapy (ERT), significantly improved oxidative stress and down-regulated miR-134a expression and the up-regulation of SIRT-1, CREB, and BDNF proteins in OVX + AD rats (p < 0.001). YPT significantly improved histological alteration compared to the OVX + AD group (p < 0.001). As a non-pharmacological treatment, YPT can improve the expression of miR-134a and SIRT-1, CREB, and BDNF proteins as much as or more than estrogen therapy, ameliorating AD-induced dementia in aged OVX rats.

Adipose-Derived Mesenchymal Stem Cells and Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging in Rats.

Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. In this study, we isolated and characterized adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of male Sprague Dawley rats. We assessed the in vitro differentiation of Ad-MSCs into epidermal progenitor cells (EPCs) using ascorbic acid and hydrocoritsone. Additionally, we induced skin aging in female Sprague Dawley rats via daily intradermal injection of D-galactose over a period of 8weeks. Then we evaluated the therapeutic potential of intradermal transplantation of Ad-MSCs and conditioned media (CM) derived from differentiated EPCs in the D-galactose-induced aging rats. Morphological assessments, antioxidant assays, and histopathological examinations were performed to investigate the effects of the treatments. Our findings revealed the significant capability of Ad-MSCs to differentiate into EPCs. Notably, compared to the group that received CM treatment, the Ad-MSCs-treated group exhibited a marked improvement in morphological appearance, antioxidant levels and histological features. These results underscore the effectiveness of Ad-MSCs in restoring skin aging as a potential therapy for skin aging.

Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial Necroptosis by Activation of RIPK1 Acetylation.

Aging is one of the most potent risk determinants for the onset of atrial fibrillation (AF). Sirts (sirtuins) have been implicated in the pathogenesis of cardiovascular disease, and their expression declines with aging. However, whether Sirts involved in age-related AF and its underlying mechanisms remain unknown. The present study aims to explore the role of Sirts in age-related AF and delineate the underlying molecular mechanisms. Sirt1 levels in the atria of both elderly individuals and aging rats were evaluated using quantitative real-time polymerase chain reaction and Western blot analysis. Mice were engineered to specifically knockout Sirt1 in the atria and right ventricle (Sirt1mef2c/mef2c). Various techniques, such as echocardiography, atrial electrophysiology, and protein acetylation modification omics were employed. Additionally, coimmunoprecipitation was utilized to substantiate the interaction between Sirt1 and RIPK1 (receptor-interacting protein kinase 1). We discerned that among the diverse subtypes of sirtuin proteins, only Sirt1 expression was significantly diminished in the atria of elderly people and aged rats. The Sirt1mef2c/mef2c mice exhibited an enlarged atrial diameter and heightened vulnerability to AF. Acetylated proteomics and cell experiments identified that Sirt1 deficiency activated atrial necroptosis through increasing RIPK1 acetylation and subsequent pseudokinase MLKL (mixed lineage kinase domain-like protein) phosphorylation. Consistently, necroptotic inhibitor necrosulfonamide mitigated atrial necroptosis and diminished both the atrial diameter and AF susceptibility of Sirt1mef2c/mef2c mice. Resveratrol prevented age-related AF in rats by activating atrial Sirt1 and inhibiting necroptosis. Our findings first demonstrated that Sirt1 exerts significant efficacy in countering age-related AF by impeding atrial necroptosis through regulation of RIPK1 acetylation, highlighting that the activation of Sirt1 or the inhibition of necroptosis could potentially serve as a therapeutic strategy for age-related AF.

3D electronic implants in subretinal space: Long-term follow-up in rodents

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime – up to 32–36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12–16 weeks. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices – 0.05 mW/mm2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 12–16 weeks, before stabilizing at about 0.08 mW/mm2. Such threshold is still significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

Glioprotective Effects of Sulforaphane in Hypothalamus: Focus on Aging Brain.

Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes.

Dysregulation of baseline and learning-dependent protein degradation in the aged hippocampus

The ubiquitin-proteasome system (UPS) controls the majority of protein degradation in cells and dysregulation of the UPS has been implicated in the pathophysiology of numerous neurodegenerative disorders, including Alzheimer’s disease. Further, strong evidence supports a critical role for the UPS in synaptic plasticity and memory formation. However, while proteasome function is known to decrease broadly in the brain across the lifespan, whether it changes in the hippocampus, a region critical for memory storage and among the first impacted in Alzheimer’s disease, at rest and following learning in the aged brain remains unknown. Further, which proteins have altered targeting for protein degradation in the aged hippocampus has yet to be explored and whether learning in advanced age interacts with changes in ubiquitin-proteasome function across the lifespan remains unknown. Here, using proteasome activity assays and unbiased proteomic analyses, we report age-dependent changes in proteasome activity and degradation-specific K48 polyubiquitin protein targeting in the hippocampus and retrosplenial cortex of male and female rats across the lifespan. In the hippocampus, the targets of altered protein degradation were involved in transcription and astrocyte structure or G-protein and Interferon signaling in males and females, respectively. Importantly, we found that contextual fear conditioning led to an increase in proteasome activity and K48 polyubiquitin protein targeting in the hippocampus of aged male rats, a result in direct contrast to what was previously reported in young adult animals. Together, these data suggest that changes in protein degradation in the hippocampus across the lifespan may be contributing to age-related memory loss.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

Impact of age-related gut microbiota dysbiosis and reduced short-chain fatty acids on the autonomic nervous system and atrial fibrillation in rats.

Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in age-related diseases, but its role in AF development remains unclear. This study aimed to investigate the correlations between changes in the autonomic nervous system, short-chain fatty acids (SCFAs), and alterations in gut microbiota in aged rats with AF. Electrophysiological experiments were conducted to assess AF induction rates and heart rate variability in rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify SCFAs in fecal samples. The study found that aged rats exhibited a higher incidence of AF and reduced heart rate variability compared to young rats. Omics research revealed disrupted gut microbiota in aged rats, specifically a decreased Firmicutes to Bacteroidetes ratio. Additionally, fecal SCFA levels were significantly lower in aged rats. Importantly, correlation analysis indicated a significant association between decreased SCFAs and declining heart rate variability in aged rats. These findings suggest that SCFAs, as metabolites of gut microbiota, may play a regulatory role in autonomic nervous function and potentially influence the onset and progression of AF in aged rats. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF.

Alleviating Acute Lung Injury Induced by Lipopolysaccharide: Dayuan Yin Suppresses Inflammation and Oxidative Stress in Elderly Male Rats.

The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore，this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY. The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS. In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB). The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses. In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.

Accumulated HIIT inhibits anxiety and depression, improves cognitive function, and memory-related proteins in the hippocampus of aged rats.

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15min, while the 3xHIIT performed three daily sessions of 5min with a 4h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.

Polygonatum polysaccharide ameliorates D-galactose-induced cognitive dysfunction in aging rats by inhibiting ferroptosis through activation of Nrf2

ContextAging is a major risk factor for various neurodegenerative diseases, and ferroptosis has been identified as an important mode of cell death during accelerated aging. As the main component of the edible plant YuZhu in China, Polygonatum polysaccharide (POP) is an important natural compound with anti-aging properties. ObjectiveTo evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved and to evaluate the overall anti-aging effects of POP on cognitive impairment due to accelerated aging. Materials and methodsA D-galactose (D-gal)-induced accelerated aging rat model was established to evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved. In turn, Morris water maze and open field experiments were used to evaluate the anti-aging effects of POP on cognitive impairment due to accelerated aging. ResultsThe mechanism by which POP affects nuclear factor E2-related factor 2 (Nrf2), an essential transcription factor, was confirmed. POP significantly improved d-gal-induced cognitive dysfunction in treated model rats, which exhibited reduced pathological changes in the hippocampus, reduced latency of the water maze platform, and increased exploration time in the central area in the open field experiment compared to those of untreated model rats. Furthermore, POP intervention downregulated ferroptosis-related proteins and upregulated Nrf2 expression, and selective inhibition of Nrf2 eliminated the ability of POP to reduce ferroptosis. ConclusionsPOP is a natural ingredient with therapeutic potential due to its ability to alleviate aging by activating Nrf2, inhibiting ferroptosis, and alleviating cognitive dysfunction.

Density of lymphocytes in cortex and medulla substance of thymus particles of white rats in normal conditions and under influence of heavy metal salts during three months

The consumption of clean water is the most relevant today, but natural water is delivered to our homes through plastic, iron and galvanized pipes. Metal ions, which are part of the pipe material, can get into drinking water and affect the human body, in particular the thymus. That is why the aim of the work was to determine the density of large, medium and small lymphocytes in the cortex and medulla of the thymus lobules of outbred white male rats of reproductive age when consuming small doses of heavy metal salts with water for three months. The study was conducted on 40 outbred white male rats of reproductive age, which were divided into 4 groups: 1 group – control animals that consumed distilled water; 2 group of animals that consumed aqueous solutions – CuSO4·5H2O at a dose of 0.247 mg/dm3; 3 group – aqueous solution of ZnSO4·7H2O at a dose of 1.505 mg/dm3; group 4 – aqueous solution of FeSO4·7H2O at a dose of 0.5 mg/dm3. Histological, electron microscopic and morphometric research methods were used to study the density of large, medium and small lymphocytes in different zones of the thymus lobules. It was found that in the control group of rats, the density of large lymphocytes is the highest in the subcapsular zone, and the lowest in the medulla. The density of medium lymphocytes is the lowest in the subcapsular zone. The density of small lymphocytes is the lowest in the medulla, and the highest in the cortico-medullary zone. When using CuSO4·5H2O salts with drinking water for three months, there were no significant changes in the density of lymphocytes compared to the control group, except for a slight decrease in the density of large lymphocytes in the cortex of the thymus lobules. The density of lymphocytes in the third group of animals that consumed zinc salts (ZnSO4·7H2O) with drinking water changes significantly: the density of large lymphocytes in the subcapsular zone decreases by 2.3 times, in the cortico-medullary zone it increases by 4.7 times, and in the medulla it increases by 2.7 times; the density of medium lymphocytes decreases in the subcapsular zone by 2 times; the density of small lymphocytes decreases by 1.5 times in the subcapsular zone, in the cortex and cortico-medullary zone – decreases by 1.2 times, and in the medulla by 1.1 times. When using FeSO4·7H2O salts with drinking water for three months, no special changes in the density of lymphocytes were noted: a decrease in the density of large lymphocytes in the subcapsular zone by 1.5 times and by 1.3 times in the cortex was observed; the density of medium lymphocytes decreases by 1.2 times in the cortex, and the density of small lymphocytes decreases by 1.2 times in the subcapsular zone and cortex, and increases by 1.2 times in the medulla, compared to the control group of animals. Ultrastructural changes in the structure of lymphocytes and reticuloepithelial cells were not detected when heavy metal salts were consumed with water. Thus, the study showed that the most toxic for the body are zinc salts (ZnSO4·7H2O), the consumption of which with drinking water in small doses for three months led to significant changes in the density of lymphocytes, compared to the control group experimental animals.