Aged Rats Research Articles

Calorie Restriction Attenuates Memory Impairment and Reduces Neuroinflammation in Obese Aged Rats.

Obesity and aging collectively potentiate inflammatory responses, particularly within the central nervous system. Managing obesity presents a significant challenge, even more so considering the context of aging. Caloric restriction (CR) has been extensively documented in the literature for its multiple health benefits. Motivated by these findings, we hypothesized that CR could serve as a valuable intervention to address the brain alterations and cognitive decline associated with obesity in aged rats. Our investigation revealed that cafeteria diet increased hippocampal and hypothalamic transcripts related to neuroinflammation, along with cognitive deficits determined in the object recognition test in 18-month-old male rats. Western blot data indicate that the obesogenic diet may disrupt the blood-brain barrier and lead to an increase in Toll-like receptor 4 in the hippocampus, events that could contribute to the cognitive deficits observed. Implementing CR after the onset of obesity mitigated neuroinflammatory changes and cognitive impairments. We found that CR increases GABA levels in the hippocampus of aged animals, as demonstrated by liquid chromatography coupled with mass spectrometry analysis. These findings underscore the potential of CR as a therapeutic opportunity to ameliorate the neuroinflammatory and cognitive alterations of obesity, especially in the context of aging.

Combination treatment with whole body vibration and simvastatin improves the early osseointegration in aged rats

BackgroundCurrent research has demonstrated that Simvastatin (SIM) and Whole Body Vibration (WBV) actively contributes to the repair of osteoporotic bones. However, there is still limited knowledge regarding the impact of this combined therapy on osseointegration in elderly individuals. Objective: The objective of this study was to verify the influence of WBV and SIM combination treatment on Titanium implants' fixation strength in aged rats. MethodsMale Sprague-Dawley rats at 24 months old were utilized for this investigation. Titanium rods were surgically inserted into the distal femoral canal on their left side. Subsequently, all animals were randomly assigned to one of four groups: Control group; WBV group; SIM group; and WBV + SIM group. Each group received Saline, Whole Body Vibration, Simvastatin, or a combination of Whole Body Vibration plus Simvastatin treatment until they reached their natural death after 12 weeks. The bilateral femurs and serum samples from these rats were collected for evaluation purposes. ResultsBoth WBV and SIM treatments exhibited an increase in bone mass, osseointegration, and push-out force compared to the Control group (all, P < 0.05). Additionally, levels of oxidative stress and inflammatory factors decreased with both treatments when compared to the Control group alone (all, P < 0.05). Notably, the WBV + SIM group displayed superior effects on new bone formation, biomechanical strength, BMP2 expression in bone tissue as well as SOD2 expression regulation related to bone repair genes when compared to other groups involved in this study (all, P < 0.05). ConclusionThese findings suggest that combining physiotherapy (WBV) with drug therapy (SIM) proves beneficial for enhancing implant fixation in aged rats.

The intersection between menopause and depression: overview of research using animal models.

Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.

Treatment of vascular dementia in female rats with AV-001, an Angiopoietin-1 mimetic peptide, improves cognitive function.

Vascular dementia (VaD) is a complex neurodegenerative disorder. We previously found that treatment of VaD in middle-aged male rats subjected to multiple microinfarction (MMI) with AV-001, a Tie2 receptor agonist, significantly improves cognitive function. Age and sex affect the development and response of VaD to therapeutic intervention. Thus, the present study investigated the therapeutic effect of AV-001 on VaD in aged female rats subjected to MMI. Female 18-month-old Wistar rats were subjected to MMI by injecting either 1,000 (low dose, LD-MMI) or 6,000 (high dose, HD-MMI) cholesterol crystals of size 70-100 μm into the right internal carotid artery. AV-001 (1 μg/Kg, i.p.) was administered once daily after MMI for 1 month, with treatment initiated 1 day after MMI. A battery of behavioral tests to examine sensorimotor and cognitive functions was performed at 21-28 days after MMI. All rats were sacrificed at 1 month after MMI. Aged female rats subjected to LD-MMI exhibit severe neurological deficits, memory impairment, and significant white matter (WM) and oligodendrogenesis injury in the corpus callosum compared with control rats. HD-MMI in aged female rats induces significant anxiety- and depression-like behaviors, which were not detected in LD-MMI aged female rats. Also, HD-MMI induces significantly increased WM injury compared to LD-MMI. AV-001 treatment of LD-MMI and HD-MMI increases oligodendrogenesis, myelin and axon density in the corpus callosum and striatal WM bundles, promotes WM integrity and attenuates neurological and cognitive deficits. Additionally, both LD-MMI and HD-MMI rats exhibit a significant increase, while AV-001 significantly decreases the levels of inflammatory factors in the cerebrospinal fluid (CSF). MMI reduces oligodendrogenesis, and induces demyelination, axonal injury and WM injury, and causes memory impairment, while HD-MMI induces increased WM injury and further depression-like behaviors compared to LD-MMI rats. AV-001 has a therapeutic effect on aged female rats with MMI by reducing WM damage and improving neuro-cognitive outcomes.

The Effect of Omega-3 Fatty Acid Supplementation and Exercise on Locomotor Activity, Exploratory Activity, and Anxiety-Like Behavior in Adult and Aged Rats.

Aging is an inevitable and complex biological process that is associated with a gradual decline in physiological functions and a higher disease susceptibility. Omega-3 fatty acids, particularly docosahexaenoic acid, play a crucial role in maintaining brain health and their deficiency is linked to age-related cognitive decline. Combining omega-3-rich diets with exercise may enhance cognitive function more effectively, as both share overlapping neurobiological and physiological effects. This study aimed to evaluate the effect of exercise and omega-3 fatty acid (FA) supplementation in two different doses (160 mg/kg and 320 mg/kg) on anxiety-like behavior and cognitive abilities in both adult and aged rats. Male Wistar rats (4-5- and 23-24-month-old) were randomly divided into seven groups: 3-week control supplemented with placebo without exercise, low-dose omega-3 FAs, high-dose omega-3 FAs, 7-week control supplemented with placebo without exercise, exercise-only, low-dose omega-3 FAs with exercise, and high-dose omega-3 FAs with exercise. The administered oil contained omega-3 FAs with DHA:EPA in a ratio of 1.5:1. Our results indicate that aging negatively impacts the locomotor and exploratory activity of rats. In adult rats, a low dose of omega-3 FAs reduces locomotor activity when combined with exercise while high dose of omega-3 FAs reduces anxiety-like behavior and improves recognition memory when combined with exercise. The combination of omega-3 FAs and exercise had varying impacts on behavior, suggesting a need for further research in this area to fully understand their therapeutic efficacy in the context of cognitive changes associated with aging.

Retraction: Yizhi Qingxin formula extract ameliorates cognitive decline in aged rats via the brain-derived neurotrophic factor/tropomyosin receptor kinase B pathway.

[This retracts the article DOI: 10.3389/fphar.2020.00510.].

Circadian rhythms of antioxidant enzymes activity, clock, and inflammation factors are disrupted in the prefrontal cortex of aged rats. Potential targets for therapeutic strategies for a healthy aging.

Age impairs cognitive functions and antioxidant defenses, for example, by increasing oxidative stress and inflammation in the brain. However, so far, there is no report on the consequences of aging on temporal patterns of proteins and lipids oxidation, antioxidant enzymes activity, endogenous clock and proinflammatory cytokine, in the prefrontal cortex (PFC). Therefore, our objectives here were: 1) to investigate the endogenous nature of 24h-rhythms of lipoperoxidation, protein carbonyls levels, CAT and GPx activity, RORa, and TNFα, in the rat PFC, and 2) to study the consequences of aging on the circadian organization of those factors in the same brain area. To do that, 3- and 22-mo-old male Holtzman rats were maintained under constant darkness conditions during 15 days before reaching the corresponding age. PFC samples were isolated every 4 h, under dim-red light, during a 24h period. Our results revealed circadian patterns of antioxidant enzymes activity, oxidative stress, RORa and TNFα proteins levels, in the PFC of young rats. The circadian distribution of the rhythms’ phases suggests the existence of a reciprocal communication among the antioxidant defenses, the endogenous clock, and the inflammation, in the PFC. Noteworthy, such circadian organization disappears in the PFC of aged rats. An increased oxidative stress would make the redox environment to change into an oxidative status, which alters the endogenous clock activity and disrupts the circadian organization of, at least part, of the antioxidant defenses and the TNFα, in the PFC. These results might highlight novel chronobiological targets for the design of therapeutic strategies addressed to a healthy aging.

Propofol ameliorates cognitive deficits following splenectomy in aged rats by inhibiting ferroptosis via the SIRT1/Nrf2/GPX4 pathway.

The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function.

Integrated renal and sympathetic mechanisms underlying the development of sex- and age-dependent hypertension and the salt sensitivity of blood pressure

Aging is a non-modifiable understudied risk factor for hypertension. We hypothesized that sympathetically mediated activation of renal sodium reabsorption drives age-dependent hypertension and the salt sensitivity of blood pressure (BP). Using 3-, 8-, and 16-month-old male and female Sprague–Dawley rats as a model of normal aging, we assessed BP, indices of sympathetic tone, and the physiological responses to acute and chronic sodium challenge including sodium chloride cotransporter (NCC) regulation. The effects of renal nerve ablation and NCC antagonism were assessed in hypertensive male rats. We observed sex-dependent impaired renal sodium handling (24 h sodium balance (meq), male 3-month 0.36 ± 0.1 vs. 16-month 0.84 ± 0.2; sodium load excreted during 5% bodyweight isotonic saline volume expansion (%) male 3-month 77 ± 5 vs. 16-month 22 ± 8), hypertension (MAP (mmHg) male 3-month 123 ± 4 vs. 16-month 148 ± 6), and the salt sensitivity of BP in aged male, but not female, rats. Attenuated sympathoinhibitory afferent renal nerve (ARN) responses contributed to increased sympathetic tone and hypertension in male rats. Increased sympathetic tone contributes to renal sodium retention, in part through increased NCC activity via a dysfunctional with-no-lysine kinase-(WNK) STE20/SPS1-related proline/alanine-rich kinase signaling pathway, to drive hypertension and the salt sensitivity of BP in aged male rats. NCC antagonism and renal nerve ablation, which reduced WNK dysfunction and decreased NCC activity, attenuated age-dependent hypertension in male Sprague–Dawley rats. The contribution of an impaired sympathoinhibitory ARN reflex to sex- and age-dependent hypertension in an NCC-dependent manner, via an impaired WNK1/WNK4 dynamic, suggests this pathway as a mechanism-based target for the treatment of age-dependent hypertension.

AGE-DEPENDENCE OF BIOCHEMICAL MANIFESTATIONS OF HEPATOTOXICINJURY IN RAT EXPOSED TO XENOBIOTICS OF VARIOUS GENESIS

Currently, the problem of liver diseases against the backdrop of the toxic effects of medicinal and industrial (herbicides) xenobiotics on the body is becoming increasingly relevant. The activation of compensatory mechanisms in response to the action of toxic agents –acetaminophen and/or diquat is closely related to age-specific features. Heightened focus on acetaminophen-induced injury is linked to the widespread use of this medication as an analgesic and antipyretic during pandemics of infectious and inflammatory diseases, especially under the conditions of warfare in Ukraine. In return, the widespread use of the herbicide diquat is accompanied by an increase in the registration of cases of diquat -induced acute poisoning. The aim of study was to evaluation the biochemical parameters of the functional state of the liver of different-aged rats under conditions of acetaminophen-and diquat-induced toxic injury. Animals were divided into three age groups: adolescent (60 days), reproductive (150 days), and mature age rats (360 days). Acute toxic injury by acetaminophen was modeled by its oral administration through gastric intubation at a daily dose of 1250 mg/kg of the animal's body weight during the last 2 days of the experiment. Acute toxic damage by diquat was modeled by a single intragastric administration using a probe at a dose of 115.5 mg/kg of the animal's body weight. The functional state of the liver was assessed on an automatic biochemical analyzer NTI Biochem FC-120.Acetaminophen intoxication led to an increase in the absolute liver mass indicator, organ index, changes in the macroscopic structure of the organ, increased serum activities of ALT and AST, total LDH, and a decrease in the De Ritis ratio amidst increased activities of ALP, GGT, and levels of total and indirect bilirubin in all age groups compared to the control. The most significant changes were observed in mature age animals (increase in ALT activity by 76%, AST by 56%, ALP by 51%, GGT by 51%, and a decrease in the De Ritis ratio by 47%). Under conditionsof diquat-induced toxic injury, a slightly different trend and degree in manifestation of established changes are observed. A more pronounced hepatotoxic effect was registered in adolescent animals, manifested by the maximum increase in absolute liver mass by 26%, ALT activity by 71%, AST by 47%, ALP by 50%, Bili-T level by 69%. No statistically significant differences compared to the control and APAP-induced injury in the activity of total LDH and GGT upon administration of toxic doses of the herbicide diquat regardless of age category were observed.Based on the experimental results, an age-related multidirectionality in the adverse effects of the medicinal xenobiotic acetaminophen and the industrial xenobiotic diquat on indicators of the morpho-functional state of the liver is observed. The most sensitive age group of animals to toxic injury by acetaminophen are rats of 360 days of age, while for diquat –60 days of age

Low-molecular-weight heparin ameliorates intestinal barrier dysfunction in aged male rats via protection of tight junction proteins.

The intestinal barrier weakens and chronic gut inflammation occurs in old age, causing age-related illnesses. Recent research shows that low-molecular-weight heparin (LMWH), besides anticoagulation, also has anti-inflammatory and anti-apoptotic effects, protecting the intestinal barrier. This study aims to analyze the effect of LMWH on the intestinal barrier of old male rodents. This study assigned Sprague-Dawley male rats to four groups: young (3months), young + LMWH, old (20months), and old + LMWH. The LMWH groups received 1mg/kg LMWH via subcutaneous injection for 7days. Optical and transmission electron microscopy (TEM) were used to examine morphological changes in intestinal mucosa due to aging. Intestinal permeability was measured using fluorescein isothiocyanate (FITC)-dextran. ELISA kits were used to measure serum levels of IL-6 and IL-1β, while Quantitative RT-PCR detected their mRNA levels in intestinal tissues. Western blotting and immunohistochemistry (IHC) evaluated the tight junction (TJ) protein levels such as occludin, zonula occludens-1 (ZO-1), and claudin-2. Western blotting assessed the expression of the apoptosis marker cleaved caspase 3, while IHC was used to detect LGR5+ intestinal stem cells. The intestinal permeability of aged rats was significantly higher than that of young rats, indicating significant differences. With age, the protein levels of occludin and ZO-1 decreased significantly, while the level of claudin-2 increased significantly. Meanwhile, our study found that the levels of IL-1β and IL-6 increased significantly with age. LMWH intervention effectively alleviated age-related intestinal barrier dysfunction. In aged rats treated with LMWH, the expression of occludin and ZO-1 proteins in the intestine increased, while the expression of claudin-2 decreased. Furthermore, LMWH administration in aged rats resulted in a decrease in IL-1β and IL-6 levels. LMWH also reduced age-related cleaved caspase3 expression, but IHC showed no difference in LGR5+ intestinal stem cells between groups. Research suggests that LMWH could potentially be a favorable therapeutic choice for age-related diseases associated with intestinal barrier dysfunction, by protecting TJ proteins, reducing inflammation, and apoptosis.

Morphofunctional changes in brain and peripheral blood in aged Wistar rats due to AlCl3 exposure

The purpose of the study: To examine morphofunctional changes of brain and peripheral blood in aged Wistar rats to observe adaptive reactions as a response on AlCl3 exposure. Methods: The work was performed on male Wistar rats, 24 months of age. Animals consumed a solution of AlCl3 100 mg/kg per day for 60 days. Morphological changes of neurons and microglia, mRNA expression levels of pro- and anti-inflammatory cytokines, microglia activation markers, amyloid-related and hypoxia-related proteins, as well as monocyte and lymphocyte subpopulations in peripheral blood, were examined. Results: AlCl3-treated old rats showed the increasing of hyperchromic neurons in 2 out of 3 examined regions of the hippocampus; morphological features of microglia cells’ dystrophy; the upregulation of pro-inflammatory cytokine Il-18 and the downregulation of anti-inflammatory cytokine Il-10, as well as App, Bace1, and Hif-1a; the decreasing of percentage of B-cells, general CD3+ lymphocyte population, including CD4+ T-helpers and CD8+ cytotoxic cells, but the increasing of CD4+/CD8+ ratio in peripheral blood. Conclusion: AlCl3-treated aged rats demonstrated systemic maladaptation to AlCl3 impact. Unlike adult rodents, aged ones have the background of inflammaging, as well as elderly people. The exposure of AlCl3 could potentially be a replacement of integral cellular and molecular processes accompanying age-related diseases, presenting in most elderly people, as an enhancer of inflammaging and hypoxia. These conditions make this model of neurodegeneration a reliable one to explore the initial mechanisms of such detrimental process, as well as prove aged rats more suitable subjects to perform future researches in this field.

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.