Aged Rats Research Articles

Protective effects of electroacupuncture on senile osteoporosis in rats.

The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms. This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague-Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks. EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups. EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.

The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

Health concerns about excess dietary salt have traditionally focused on its relationship with hypertension and the increased risk of cognitive impairment. However, research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, particularly regarding disease prevention and treatment strategies for women. The present study examined aged female rats over 12 weeks, using control, low, and high salt diets to mimic the post-menopausal phase in human females when cardiovascular risks typically increase. Cardiometabolic parameters and cognition were monitored. The findings revealed the impact of varying salt diets on blood lipids, blood pressure (BP) and heart rate (HR) levels and variability, anxiety, and cognition. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Aged female rats exhibited increased anxiety on the low-salt diet at the fourth week, but the anxiety began to improve starting from the eighth week. Additionally, a trend suggested that the low salt intake worsened short-term memory while improving long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on a high-salt diet compared to those on a low-salt diet. The study provides valuable insights into the effects of salt intake on cardiometabolic parameters and cognitive function in aged female rats, highlighting the importance of considering sex-specific dietary guidelines for cardiometabolic and cognitive health.

Concrete-Inspired Bionic Bone Glue Repairs Osteoporotic Bone Defects by Gluing and Remodeling Aging Macrophages.

Osteoporotic fractures are characterized by abnormal inflammation, deterioration of the bone microenvironment, weakened mechanical properties, and difficulties in osteogenic differentiation. The chronic inflammatory state characterized by aging macrophages leads to delayed or non-healing of the fracture or even the formation of bone defects. The current bottleneck in clinical treatment is to achieve strong fixation of the comminuted bone fragments and effective regulation of the complex microenvironment of aging macrophages. Inspired by cement and gravel in concrete infrastructure, a biomimetic bone glue with poly(lactic-co-glycolic acid) microspheres is developed and levodopa/oxidized chitosan hydrogel stabilized on an organic-inorganic framework of nanohydroxyapatite, named DOPM. DOPM is characterized via morphological and mechanical characterization techniques, in vitro experiments with bone marrow mesenchymal stromal cells, and in vivo experiments with an aged SD rat model exhibiting osteoporotic bone defects. DOPM exhibited excellent adhesion properties, good biocompatibility, and significant osteogenic differentiation. Transcriptomic analysis revealed that DOPM improved the inflammatory microenvironment by inhibiting the NF-κB signaling pathway and promoting aging macrophage polarization toward M2 macrophages, thus significantly accelerating bone defect repair and regeneration. This biomimetic bone glue, which enhances osteointegration and reestablishes the homeostasis of aging macrophages, has potential applications in the treatment of osteoporotic bone defects.

Spermidine protects cellular redox status and ionic homeostasis in D-galactose induced senescence and natural aging rat models.

Impaired redox homeostasis is an important hallmark of aging. Among various anti-aging interventions, caloric restriction mimetics (CRMs) are the most effective inpromoting health and longevity. The potential role of spermidine (SPD) as a CRM in modulating oxidative stress and redox homeostasis during aging remains unclear. Thisstudy aimed to investigate the protective effect of SPD inD-galactose (D-gal) accelerated induced senescence model and naturally aged rats. Young male rats (4months), D-gal induced (500 mg/kg b. w., subcutaneously) aging model and naturally aged (22months) rats were supplemented with SPD (10 mg/kg b. w., orally) for 6weeks. The results showed that SPD supplementation suppresses the age induced increase in reactive oxygen species, lipid peroxidation andprotein oxidation. Additionally, it increases the level ofantioxidants, plasma membrane redox system in erythrocytes and membrane. These results also indicate that membrane transporter activity is correlated with the susceptibility of the erythrocyte towards oxidative damage. We therefore present evidence that SPD improves redox status and membrane impairments in erythrocytes in experimental and naturally aging rat models, however, more research is required to recommend a potential therapeutic role for SPD as an anti-aging intervention strategy.

Preparation and characterization of W/O/W purple potato anthocyanin nanoparticles: Antioxidant effects and gut microbiota improvement in rats.

Purple potato anthocyanins (PPAs) are recognized for their broad physiological activities, including significant antioxidant, antimicrobial, and gut microbiota-regulating effects. However, their limited bioavailability in biological systems restricts the full realization of these potentials. In order to improve the bioavailability of PPA, this paper established and optimized the preparation process of W/O/W purple potato anthocyanin nanoparticles (PPA-NPs). Based on the determination of the metabolites of PPA-NPs, in vivo experiments were conducted in rats to investigate the absorption and metabolism, antioxidant activity, and the impact on the intestinal microbiota of PPA-NPs. UPLC-Q-TOF-MSMS analysis showed that the absorption of anthocyanins was increased by 220.36% in rats gavaged with PPA-NPs compared to rats gavaged with PPA directly. Subsequent in vivo experiments revealed that PPA-NPs significantly bolster primary antioxidant markers, evidenced by elevated glutathione and superoxide dismutase levels and reduced malondialdehyde content. Moreover, PPA-NPs were found to positively alter the gut microbiome structure in aged rats, notably increasing the abundance of beneficial bacteria, such as Lactobacillus and Rothia, and improving microbial diversity. These findings suggest that W/O/W PPA-NPs markedly improve the bioavailability of PPAs, showcasing promising antioxidant properties and potential health benefits for gut health in vivo. Overall, this research presents a novel approach for developing nanodelivery systems aimed at enhancing the bioavailability of water-soluble substances.

Correlations between Metabolic Parameters, Blood Cytokine Levels, and Behavioral Parameters in Male and Female Rats of Different Age after Intrauterine Stress.

We studied interrelationships between behavioral parameters, metabolic processes, and cytokine content in the blood of male and female rats at different stages of postnatal ontogeny after intrauterine stress (mothers were forced to swim in cold water from the 10th to the 16th day of pregnancy). Correlations between behavioral and metabolic parameters in prenatally stressed rats were revealed at an earlier age (day 21 of life) than in controls. In comparison with intact rats, in males exposed to intrauterine stress no relationships between these parameters were revealed at older age, while in females, their direction and character change on day 60 of life. In prenatally stressed males, correlations of the blood levels of IL-6 were revealed: inverse relationships with behavioral parameters on the days 21 and 30 and direct relationships with metabolic parameters on day 60 of life. In prenatally stressed females on day 30 of life, we observed negative correlations between IL-4 levels and metabolic parameters that were absent under normal conditions. Thus, intrauterine stress leads to reorganization of the relationships between the parameters of metabolic and immune processes, which are essential for the purposeful behavior of mammals. The effects of stress seem to depend on the sex of the offspring and stage of postnatal development.

Fish Oil Supplement Mitigates Muscle Injury In Vivo and In Vitro: A Preliminary Report.

Background: Following injury, older adults exhibit slow recovery of muscle function. Age-related impairment of sarcolemmal membrane repair may contribute to myocyte death, increasing the need for myogenesis and prolonging recovery. Dietary fish oil (FO) is a common nutritional supplement that may alter plasma membrane composition to enhance the response to membrane injury. Methods: We assessed effects of an 8-week dietary intervention on muscle contractile recovery in aged (22 mo.) rats on control (n = 5) or FO (control + 33 g/kg FO (45% eicosapentaenoic acid; 10% docosahexaenoic acid); n = 5) diets 1-week after contusion injury, as well as adult (8 mo., n = 8) rats on the control diet. Results: Recovery was reduced in aged rats on the control diet vs. adults (63 vs. 80%; p = 0.042), while those on the FO diet recovered similarly to (78%) adults. To directly assess sarcolemma injury, C2C12 cells were cultured in media with and without FO (1, 10, and 100 μg/mL; 24 or 48 h) and injured with an infrared laser in medium containing FM4-64 dye as a marker of sarcolemmal injury. FO reduced the area under the FM4-64 fluorescence-time curve at all concentrations after both 24 and 48 h supplementation. Conclusions: These preliminary data suggest FO might aid recovery of muscle function following injury in older adults by enhancing membrane resealing and repair.

Anticancer Potential of Ethanolic Extract of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) Dried Fruits on Breast Adenocarcinoma: In Vitro and In Vivo Evidences.

Breast cancer incidence and mortality rate in Cameroonian women is incredibly high, thus there is need for more effective therapy. Xylopia aethiopica dry fruits are traditionally used for both nutritional and medicinal purposes, including the management of diverse ailments such as cancer. This study evaluated the in vitro and in vivo anti-mammary cancer potential of X. aethiopica. The cytotoxic activity of the ethanolic extract of X. aethiopica dry fruits was assessed at different concentrations against MDA-MB 231 and MCF-7 cells using the MTT assay. Additionally, clone formation, apoptosis/necrosis, cell adhesion, cell migration, and chemotaxis were examined. Furthermore, the chemo-preventive potential of X. aethiopica dry fruit extract (XAE) was evaluated on breast tumors induced by DMBA in 42 female rats of age 45-55 days (~80 g). The normal (NOR) and negative (DMBA) control groups were daily treated with the vehicle, while the positive (Tamox) and test (XAE) groups were administered tamoxifen (3.3 mg/kg) and X. aethiopica extract (75, 150, and 300 mg/kg BW), respectively for 20 weeks. Parameters such as tumor volume and burden, tumor incidence, CA 15-3 serum level, inflammatory status, antioxidant and histopathology were evaluated. X. aethiopica significantly (p < 0.05) decreased ER+ (MCF-7) and ER- (MDA-MB 231) breast adenocarcinoma cell growth from 12.5 to 100 μg/mL after 72 h. At the 100 μg/mL concentration, clone formation, cell proliferation, and migration were notably decreased in MDA-MB 231 cells after 48 h, while there was an observed rise in cell adhesion to the collagen extracellular matrix. Additionally, there was a rise in apoptotic cell count (p < 0.01) and caspase-3 activity (p < 0.05) observed in MDA-MB 231 cells following exposure to XAE at 100 μg/mL. XAE, across all tested doses, demonstrated significant reductions in tumor incidence, burden, and volume, akin to tamoxifen, compared to untreated rats (DMBA). Furthermore, there was an elevation in antioxidants (SOD, CAT, and GSH) and a decrease in pro-inflammatory cytokines (INF-γ, TNF-α, IL-12, and IL-6) observed at all tested doses. Overall, X. aethiopica dry fruit displays anticancer potential through caspase-3-dependent apoptosis pathways, alongside antioxidant and anti-inflammatory activities.

Natural pesticide, Azadirachta indica A. Juss. (Neem), disrupted reproductive parameters of male rats

Ethnopharmacological relevanceNeem (Azadirachta indica A. Juss.) is native to India and belongs to the Meliaceae family. It has been used for centuries in Eastern medicine, and more recently, as a natural pesticide. Although the use of bioinsecticides is supported by organic food production, further research is needed on each formulation, particularly on their effects on organisms. Aim of the studyThis study evaluated the reproductive toxicity of an aqueous extract of neem leaves in male Wistar rats of reproductive age after eight days of exposure. Materials and methodsFor this study, 20 rats were divided into four groups of five animals each and treated with different concentrations: Group 1 received 10,000 ppm, Group 2 received 7500 ppm, Group 3 received 5000 ppm, and Group 4 served as the control, received distilled water. The animals were observed for eight days for any clinical signs of toxicity. Semen quality, including sperm motility and viability, was analyzed. ResultsNo significant differences in physiological changes were observed between treatments. However, sperm motility and viability were affected in a concentration-dependent manner, with the group that received the highest dose exhibiting inviable spermatozoa. ConclusionThe data suggested that the administered doses had low toxicity. Nevertheless, concerns regarding reproductive toxicity remain because motility and sperm viability are negatively affected at the highest dose. Although bioinsecticides are widely used in organic food production, further research on each formulation, particularly regarding their long-term effects on organisms, is required.

High-intensity interval training, but not Spirulina supplementation, changes muscle regeneration signaling proteins in aged rats with obesity and diabetes.

This study aimed to investigate changes in protein signaling associated with muscle regeneration in aged rats with obesity and diabetes following high-intensity interval training (HIIT) and SP supplementation. Forty male Wistar rats weighting 280-325 g were used in this study. Obesity was induced by eight weeks of a high-fat diet, and diabetes was induced by intraperitoneal injection of 40 mg/kg streptozocin. Rats were randomly divided into control (CON), sham, SP, HIIT, and HIIT+SP groups. HIIT was performed five times per week during the 8-week period. SP dose was 50 mg/kg. Real-time PCR was used to evaluate the expression of myogenin, MyoD1, and Pax7. The decreases in body mass in the HIIT, HIIT+SP and SP groups were significantly higher than those in the sham and CON groups (p=0.0001). The soleus muscle mass increased significantly only in the HIIT and HIIT+SP groups (p<0.01). HIIT+SP improved fasting blood glucose and insulin levels more than HIIT alone and SP (p<0.05), while HIIT increased the expression levels of myogenic factors more than other groups (p=0.0001). In conclusion HIIT alone had a significant impact on myogenic factors, whereas Spirulina had an effect only when combined with HIIT.

Protective Effects of Cervus elaphus and Eucommia ulmoides Mixture (KGC01CE) on Muscle Loss and Function in Aged Rats.

Sarcopenia is a condition characterized by a progressive loss of muscle mass and function which are influenced by certain factors such as aging, nutritional deficiencies, and chronic diseases. Despite numerous efforts to prevent or treat sarcopenia, effective therapeutic options for this disease remain limited. This study aims to evaluate the effects of KGC01CE treatment, a mixture of Cervus elaphus (Ce) and Eucommia ulmoides (Eu), which are well-known traditional herbal medicines in Asia, on age-related muscle loss and functional decline in aged rats. KGC01CE has been found to be more effective than the individual extracts in inhibiting dexamethasone (DEX)-induced muscle atrophy and improving muscle mass and grip strength in C2C12 cells and aged rats. Moreover, animal studies were conducted to determine the minimum effective dose, and a 12-week oral administration of KGC01CE treatment at doses of 50, 100, and 200 mg/kg to 15-month-old aged rats resulted in a dose-dependent increase in lean mass, muscle mass, grip strength, and muscle cross-sectional area (CSA), which had decreased due to aging. Furthermore, it was shown that KGC01CE activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and inhibited the expression of muscle-degrading proteins MuRF, Atrogin-1, and myostatin. These results suggest that KGC01CE treatment may effectively prevent muscle loss and functional decline, providing a novel therapeutic strategy for sarcopenia.

PTPN2 dephosphorylates STAT3 to ameliorate anesthesia-induced cognitive decline in aged rats by altering the microglial phenotype and inhibiting inflammation

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

Study of Histological Changes of Testis in Rats of Different Ages When Exposed to Frequency 10GHZ Within The X-Band Microwave

This study investigates the impact of 10 GHz microwave exposure, within the X-band range, on rat testicular tissue and sperm development across different age groups. Laboratory rats were divided into a control group of six, which was not exposed to microwaves, and a treatment group of 18, further split into three age-based subgroups (8–12 weeks, 12–16 weeks, and 16–20 weeks), each containing six rats exposed to 10 GHz microwaves for 2.5 hours daily over five weeks. The findings revealed no histological changes in the control group. However, in the treated groups, significant alterations were observed: the youngest group showed a lack of sperm formation and loss of spermatocytes; the middle group displayed malformed sperm and reduced numbers; and the oldest group experienced a decrease in sperm count and minor shape alterations. Additionally, after five weeks, all treated groups exhibited damage to the testicular interstitial tissue, including ruptures and space formation between seminiferous tubules. This study suggests potential risks of microwave exposure on reproductive health and lays the groundwork for future research in this area.

Elucidating the Mechanism of Large-Diameter Titanium Dioxide Nanotubes in Protecting Osteoblasts Under Oxidative Stress Environment: The Role of Fibronectin and Albumin Adsorption.

Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear. This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved. Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110. In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30. TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients.

Neuroinflammation inhibition and neuroprotective effects of purpurin, a potential anti-AD compound, screened via network proximity and gene enrichment analyses.

Alzheimer's disease (AD) is a complex neurodegenerative disease without any effective preventive or therapeutic drugs. Natural products with stable structures and pharmacological characteristics are valuable sources for the development of novel drugs for many complex diseases. This study aimed to discover potential natural compounds for the treatment of AD using new technologies and methods and explore the efficacy and mechanism of candidate compounds. AD-related large-scale genetic datasets were collated to construct disease-PPIs and natural products were collected from six databases to construct compound-protein interactions (CPIs). Potential relationships between natural compounds and AD were predicted via network proximity and gene enrichment analyses. Then, five AD-related cell models and d-galactose-induced aging rat model were established to evaluate the neuroprotective effects of candidate compounds in vitro and in vivo. We identified that 267 natural compounds were predicted to have close connections with AD and 19 compounds could exert protective effect in at least one cell model. Notably, purpurin exerted protective effect in three cell models and significantly improved the cognitive learning and memory functions, reduced the oxidative stress injuries and neuroinflammation, and enhanced the synaptic plasticity and neurotrophic effect in the brain of d-galactose-treated rats. In this study, AD-related natural compounds were identified via network proximity and gene enrichment analyses. In vivo and in vitro experiments revealed the therapeutic potential of purpurin for AD treatment, laying the foundation for further in-depth research and providing valuable information for the development of novel anti-AD drugs.

Activity of the hypothalamic neuropeptide Y increases in adult and decreases in old rats.

Middle-aged obesity and aging anorexia with muscle loss (sarcopenia) of old people present public health burden. These alterations may appear both in humans and rodents suggesting the role for regulatory alterations. Previously, we demonstrated that biphasic changes in the weight-reducing (catabolic) effects of neuropeptides of the hypothalamus-adipose tissue axis (e.g. leptin) may contribute to both trends. With regard to the anabolic effects of the hypothalamic neuropeptide Y (NPY) inhibited by leptin, we hypothesized non-linear age-related changes with shifts in the opposite directions. We investigated the orexigenic and hypometabolic effects of intracerebroventricularly administered NPY (hyperphagia induced by NPY injection or changes in food intake, body weight, heart rate, body temperature, locomotor activity during a 7-day NPY infusion), the immunoreactivity and gene expression of NPY in the hypothalamic arcuate nucleus of male Wistar rats of five age groups from young to old. The orexigenic/hypometabolic efficacy and the immunoreactivity of NPY increased in middle-aged animals preceding the peak of adiposity observed in aging rats, then decreased preceding anorexia and weight loss in old rats. These shifts may contribute to the development of both age-related obesity and aging anorexia, sarcopenia, and should be considered in future drug development targeting the NPY system.

Effect of ethanol leaf extract of Moringa oleifera on D-galactose induced changes in lipid profile of aged Wistar rats

Uncontrolled hyperlipidaemia is linked to some age-related diseases like obesity, diabetes mellitus, and cardiovascular diseases. To examine the blood lipid profile in wistar rats, this study employed D-galactose-induced aging as a model. The lipid profiles were analysed using standard methods. Thirty (30) male albino rats were randomly assigned into five (5) groups of six (6) rats each and fed with basal diets. Group 1 and 5 which served as the young and adult controls respectively received basal diet only while the others were administered D-galactose (150mg/kg) and Moringa oleifera extract (MOLE-200mg/kg and 400mg/kg) respectively for eight (8) weeks. At the end of the study rats were sacrificed and blood samples were collected. At week 0, the results of the total cholesterol concentrations (98.81 ± 6.43), TAG (69.15 ± 1.34), LDL-cholesterol (31.80 ± 4.10), VLDL-cholesterol (13.83 ± 0..27) and HDL-cholesterol (35.64 ± 2.81) in rats administered M. oleifera leaf extract, D-galactose and distilled water respectively showed no significant (P &gt; 0.05) difference across all the groups but at week 8 treatment with high dose of MOLE resulted in a significant (P ≤ 0.05) decrease in total serum cholesterol (112.45 ± 3.05), TAG (114.05 ± 5.47), LDL-cholesterol (19.66 ± 4.06) concentrations relative to the D-galactose only treated group. Conversely, HDL-cholesterol concentration was significantly increased (P ≤ 0.05) following treatment with both low (69.53 ± 1.94) and high dose (69.99 ± 2.64) of MOLE relative to the D-galactose (63.65 ± 2.54) treated group. These results suggest that Moringa oleifera leaf extract exerts an anti-hyperlipidaemic effect against D-galactose-induced toxicity and thus could confer protection against aging.

Combined Treatment with Tauroursodeoxycholic Acid and SCD Probiotics Reduces Oxidative Stress in Lung Tissue of Aged Rats

Aging is associated with an increased level of oxidative stress, resulting from an elevated production of reactive oxygen species, which can lead to cellular and tissue damage, particularly in the lungs. This study examined the effects of Tauroursodeoxycholic acid (TUDCA) and SCD Probiotics, both individually and in combination, on oxidative stress markers in the lung tissue of aged Sprague-Dawley rats. The primary objective was to assess the potential of these agents in reducing malondialdehyde (MDA), advanced oxidation protein products (AOPP), and myeloperoxidase (MPO) levels, which are indicative of oxidative damage and inflammation. The results showed that TUDCA significantly decreased MDA and AOPP levels, suggesting its role in maintaining mitochondrial stability and inhibiting apoptotic pathways. SCD Probiotics also demonstrated a reduction in AOPP levels, highlighting their immunomodulatory and antioxidant effects. Furthermore, the combined treatment of TUDCA and SCD Probiotics led to a more pronounced decrease in both MDA and AOPP levels, along with a significant reduction in MPO activity. This suggests a synergistic interaction that enhances the antioxidative and anti-inflammatory properties of the individual treatments. These findings support the therapeutic potential of TUDCA and SCD Probiotics in mitigating oxidative damage in aging lung tissues, proposing that their concurrent use could be an effective strategy against age-related oxidative stress. Further research is warranted to explore these effects across different models and long-term applications.

Resistance training suppresses accumulation of senescent fibro-adipogenic progenitors and senescence-associated secretory phenotype in aging rat skeletal muscle

AbstractAccumulation of senescent cells in tissues contributes to multiple aging-related pathologies. Senescent fibro-adipogenic progenitors (FAPs) contribute to aging-related muscle atrophy. Resistance training can help to maintain skeletal muscle mass, improve mobility, and reduce certain health risks commonly associated with aging. We investigated, using rat model, the impact of resistance training on FAPs in aging skeletal muscle, which remains unclear. Twenty-two-month-old female rats were divided into sedentary and training groups. The training group rodents were trained to climb a ladder while bearing a load for 20 training sessions over 2 months, after which, the flexor hallucis longus muscles were collected and analyzed. Senescent cells were identified using a senescence-associated β-galactosidase stain and p21 immunohistochemistry (IHC), and FAPs were identified using platelet-derived growth factor receptor alpha IHC. The results indicate that resistance training in rats prevented aging-associated skeletal muscle atrophy and suppressed M2 polarization of macrophages. The number of senescent cells was significantly reduced in the 24-month-old training group, with most of them being FAPs. Conversely, the number of senescent FAPs increased significantly in the 24-month-old sedentary group compared with that in the 18-month-old sedentary group. The number of senescent FAPs in the 24-month-old training group decreased significantly. Resistance training also suppressed the senescence-associated secretory phenotype (SASP). The killer T cell-specific marker, CD8α, was elevated in the skeletal muscles of the aging rats following resistance training, indicating upregulation of recognition and elimination of senescent cells. Overall, resistance training suppressed the accumulation of senescent FAPs and acquisition of SASP in aging skeletal muscles.

Research on the mechanism of buyang huanwu decoction in the amelioration of age-associated memory impairment based on the “co-occurrence network regulation of intestinal microecology-host metabolism-immune function”

Ethnopharmacological relevanceBrain aging can promote neuronal damage, contributing to aging-related diseases like memory dysfunction. Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula known for tonifying qi and activating blood circulation, shows neuroprotective properties. Despite this, the specific mechanism by which BYHWD improves age-associated memory impairment (AAMI) has not been explored in existing literature. Aim of the studyThis study aimed to investigate the mechanism of BYHWD in the improvement of AAMI based on the “co-occurrence network regulation of intestinal microecology-host metabolism-immune function”. Materials and methodsFirstly, D-galactose was performed to induce a rat model of AAMI. Learning and memory deficits was assessed by the Morris water maze test. H&E and Nissl staining were used to observe the pathological changes in neurons in the hippocampus of rats. Meanwhile, the levels of pro-inflammatory cytokines and the activation of antioxidant enzymes in rat serum were measured using ELISA. Finally, an integrated pharmacological approach was applied to explore the potential mechanism of BYHWD in improving AAMI. ResultsOur results indicated that BYHWD significantly mitigated the pathological structure of the hippocampus, reversed the levels of IL-6, TNF-α, GSH, and CAT in the serum, and improved learning and memory in aging rats. Transcriptomics combined with network pharmacology showed that energy metabolism and the inflammatory response were the key biological pathways for BYHWD to ameliorate AAMI. Integrative analysis of the microbiome and metabolomics revealed that BYHWD has the potential to restore the balance of abundance between probiotics and harmful bacteria, and ameliorate the reprogramming of energy metabolism caused by aging in the brain. The co-occurrence network analysis demonstrated that a strong correlation between the treatment of AAMI and the stability of intestinal microecology, host metabolism, and immune network. ConclusionThe findings of this study collectively support the notion that BYHWD has a superior therapeutic effect in an AAMI rat model. The mechanism involves regulating the “intestinal microecology-metabolism-immune function co-occurrence network” system to restore the composition of gut microbiota and metabolites. This further improves the metabolic phenotype of brain tissue and maintains the homeostasis of central nervous system's immunity, leading to an improvement in AAMI. Consequently, this study offers a unique perspective on the prevention and treatment of AAMI. And, BYHWD is also considered to be a promising preclinical treatment for improving AAMI.