Aged Rats Research Articles

Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis.

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats. This paper aimed to explore the role and mechanism of BJTW in ameliorating iron overload-induced bone loss. Furthermore, BJTW effectively improved the bone micro-structure of the femur in mice, and altered bone metabolism biomarkers alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, as well as oxidative indexes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) glutathione (GSH) and malondialdehyde (MDA) in liver. As for network pharmacology, 73 components collected from BJTW regulated 99 common targets merged in the BJTW and OP. The results of RNA-seq indicated that there were 418 potential targets in BJTW low dose group (BJTW-L) and 347 potential targets in BJTW high dose group (BJTW-H). Intriguingly, both PI3K-AKT signaling pathway and the AGEs-RAGE signaling pathway were contained in the KEGG pathways enrichment results of network pharmacology and transcriptomics, which were considered as the potential mechanism. Additionally, we verified that BJTW regulated the expression of related proteins in RAGE/PI3K-AKT pathways in MC3T3-E1 cells. In summary, BJTW has potent effect on protecting against iron overload-induced OP, and its mechanism may be related to the activation of the RAGE/PI3K-AKT signaling pathways.

NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes' mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.

Differential impact of unilateral stroke on the bihemispheric motor cortex representation of the jaw and tongue muscles in young and aged rats.

Dysphagia commonly occurs after stroke, yet the mechanisms of post-stroke corticobulbar plasticity are not well understood. While cortical activity associated with swallowing actions is bihemispheric, prior research has suggested that plasticity of the intact cortex may drive recovery of swallowing after unilateral stroke. Age may be an important factor as it is an independent predictor of dysphagia after stroke and neuroplasticity may be reduced with age. Based on previous clinical studies, we hypothesized that cranial muscle activating volumes may be expanded in the intact hemisphere and would contribute to swallowing function. We also hypothesized that older age would be associated with limited map expansion and reduced function. As such, our goal was to determine the impact of stroke and age on corticobulbar plasticity by examining the jaw and tongue muscle activating volumes within the bilateral sensorimotor cortices. Using the middle cerebral artery occlusion rat stroke model, intracortical microstimulation (ICMS) was used to map regions of sensorimotor cortex that activate tongue and jaw muscles in both hemispheres. Young adult (7 months) and aged (30 months) male F344 × BN rats underwent a stroke or sham-control surgery, followed by ICMS mapping 8 weeks later. Videofluoroscopy was used to assess oral-motor functions. Increased activating volume of the sensorimotor cortex within the intact hemisphere was found only for jaw muscles, whereas significant stroke-related differences in tongue activating cortical volume were limited to the infarcted hemisphere. These stroke-related differences were correlated with infarct size, such that larger infarcts were associated with increased jaw representation in the intact hemisphere and decreased tongue representation in the infarcted hemisphere. We found that both age and stroke were independently associated with swallowing differences, weight loss, and increased corticomotor thresholds. Laterality of tongue and jaw representations in the sham-control group revealed variability between individuals and between muscles within individuals. Our findings suggest the role of the intact and infarcted hemispheres in the recovery of oral motor function may differ between the tongue and jaw muscles, which may have important implications for rehabilitation, especially hemisphere-specific neuromodulatory approaches. This study addressed the natural course of recovery after stroke; future work should expand to focus on rehabilitation.

Effects of boric acid on oxidant-antioxidant, proinflammatory cytokine levels, and biochemical parameters in aged rats

Purpose: As a result of the literature studies, it was seen that boric acid was the subject of many studies, and its effects on living things were investigated and examined. The aim of this study was to investigate the effects of oral boric acid supplementation at pharmacologic doses on physiological and biochemical systems in aged rats.
 Material and methods: A total of 32 Wistar Albino male-aged rats were randomly and equally divided into the following four groups: 1st; Control=1 ml saline; 2nd; Low-dose boric acid (L-BA)=10 mg/kg; 3rd; Medium-dose boric acid (M-BA)=20 mg/kg; 4th; High-dose boric acid (H-BA)=40 mg/kg. Boric acid was given orally to aged rats for 28 days. Blood, liver, and kidney samples of rats were collected on day 29 to be analyzed for oxidants, antioxidants, proinflammatory cytokines, and biochemical changes.
 Result: Boric acid significantly increased albumin, total protein, calcium levels equally in all boric acid groups compared to the control group (p

Changes in Paraoxonase, β-Glucosidase, and Carbonic Anhydrase Enzymes Related to Age and Scopolamine-Induced Memory Impairment in Rats

This study aimed to investigate the changes in Paraoxonase (PON), Carbonic Anhydrase (CA), and β-glucosidase levels of different aged rats and scopolamine-induced memory impairment rats. This study used young, adult, and middle-aged male Wistar Albino rats. Scopolamine was administered as a single dose/multiple doses and a Morris water maze (MWM) was used for spatial learning testing in rats. Enzyme-linked immunosorbent assays (ELISAs) were used to determine serum and liver PON and β-glucosidase levels. The CA enzyme activity was assayed following the hydration of CO2. As a result of the comparison of age-related and scopolamine-related changes in PON and β-glucosidase levels in liver and serum samples, no significant age-related and scopolamine-effective changes were observed in serum, while liver PON and liver β-glucosidase levels were found to change significantly. CA activity studies, on the other hand, showed that adults have the lowest CA activity compared to young and middle-aged groups and scopolamine inhibited CA activity in vivo. We found that adult rats modeled with memory impairment had statistically lower levels of liver PON and liver β-glucosidase. CA activity was also found to be significantly reduced. β-glucosidase and CA should be further investigated in terms of neurodegenerative disease risk factors, just like PON, whose importance has been determined by numerous studies in the literature.

Investigation of Potential Protective effects of Betanin on experimental Monosodium Glutamate–induced toxicity in Elderly rats

This study was conducted to investigate the protective effects of Betanin active ingredient in red beetroot plant (Beta vulgaris) in elderly rats exposed to chronic toxicity of monosodium glutamate (MSG). A total of 48 elderly rats were randomly divided into 4 different groups. At the end of the 28–day study, the rats were sacrificed under deep anesthesia. Total antioxidant capacity (TAC), total oxidant capacity (TOC), paraoxonase (PON), thiol, malondialdehyde (MDA), and nitric oxide (NO) levels were investigated in rat blood serum using the spectrophotometric method. Oxidative Stress Index (OSI) was calculated by dividing TOC by TAC. Total bilirubin was measured with the colorimetric method using an ELISA kit. Liver tissues were stained with hematoxylin–eosin (HE) for histopathological examination. The difference in serum levels of TAC, TOC, OSI, PON, MDA, and thiol was statistically significant between the groups (P<0.05). The difference in serum levels of NO and total bilirubin was not statistically significant between the groups (P>0.05). The analysis of histopathological findings revealed uncommon mild hydropic degeneration in the MSG group and almost normal histological appearance in the MSG+Betanin group. This study demonstrated that betanin could increase the antioxidant effect and reduce the histopathological damage caused by MSG.

Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats

ObjectiveAnesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration.MethodsRats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2’s effect on tau phosphorylation.ResultsSevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats.ConclusionSevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

Complex alterations in inflammatory pain and analgesic sensitivity in young and ageing female rats: involvement of ASIC3 and Nav1.8 in primary sensory neurons.

Our aim was to determine an age-dependent role of Nav1.8 and ASIC3 in dorsal root ganglion (DRG) neurons in a rat pre-clinical model of long-term inflammatory pain. We compared 6 and 24months-old female Wistar rats after cutaneous inflammation. We used behavioral pain assessments over time, qPCR, quantitative immunohistochemistry, selective pharmacological manipulation, ELISA and in vitro treatment with cytokines. Older rats exhibited delayed recovery from mechanical allodynia and earlier onset of spontaneous pain than younger rats after inflammation. Moreover, the expression patterns of Nav1.8 and ASIC3 were time and age-dependent and ASIC3 levels remained elevated only in aged rats. In vivo, selective blockade of Nav1.8 with A803467 or of ASIC3 with APETx2 alleviated mechanical and cold allodynia and also spontaneous pain in both age groups with slightly different potency. Furthermore, in vitro IL-1β up-regulated Nav1.8 expression in DRG neurons cultured from young but not old rats. We also found that while TNF-α up-regulated ASIC3 expression in both age groups, IL-6 and IL-1β had this effect only on young and aged neurons, respectively. Inflammation-associated mechanical allodynia and spontaneous pain in the elderly can be more effectively treated by inhibiting ASIC3 than Nav1.8.

Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats.

Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC. In this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats. We found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning. These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury.

Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia-reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q10 (CoQ10 ) in myocardial IR injury of aged male rats. Seventy-two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ10 , MT, combination therapy (MT+CoQ10 ) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500µL of a respiration buffer containing 6×106 ± 5×105 mitochondria/mL) in MT-receiving groups at the onset of reperfusion. CoQ10 (10mg/kg/day) was injected intraperitoneally for 2weeks before IR induction. Twenty-four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ10 improved haemodynamic index changes and reduced IS and LDH release (P<0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P<0.05). CoQ10 also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.

Effects of moxibustion at "Zusanli" (ST 36) on oxidative stress and intestinal flora in aging rats.

To observe the effects of moxibustion at "Zusanli"(ST 36)on oxidative stress and intestinal flora in subacute aging rats, and to explore the possible mechanism of moxibustion in delaying aging. Thirty SD rats were randomly divided into a blank group, a model group and a Zusanli group, with 10 rats in each group. Subacute aging model was established by intraperitoneal injection of D-galactose at dosage of 500 mg/kg in the model group and the Zusanli group, once a day for 42 days. In the Zusanli group, moxibustion was applied at bilateral "Zusanli" (ST 36) , once a day, 3 moxa cones at each acupoint, for consecutive 28 days. After intervention, the serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA; the intestinal flora was detected by 16S rRNA sequencing technique in each group. Compared with the blank group, the serum level of SOD was decreased (P<0.01), the serum level of MDA was increased (P<0.01) in the model group. Compared with the model group, the serum level of SOD was increased (P<0.01), the serum level of MDA was decreased (P<0.01) in the Zusanli group. Compared with the blank group, Chao1 and Shannon indexes were decreased in the model group (P<0.01, P<0.05). Compared with the model group, Chao1 and Shannon indexes were increased in the Zusanli group (P<0.01, P<0.05). Compared with the blank group, the relative abundance of Firmicutes, Treponema_2 and Lachnospiraceae_NK4A136_group was increased (P<0.05, P<0.01), while the relative abundance of Prevotellaceae_UCG-003 and the relative abundance ratio of Bacteroidetes and Firmicutes (B/F value) were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the relative abundance of Firmicutes and Treponema_2 was decreased (P<0.01), while the relative abundance of Bacteroidetes, Lactobacillus, Prevotellaceae_UCG-003 and B/F value were increased (P<0.05, P<0.01) in the Zusanli group. Moxibustion at "Zusanli"(ST 36)can effectively improve the level of oxidative stress, regulate the constitution of intestinal flora, maintain the microecological balance of intestinal flora in aging rats, and thus play a role in delaying aging.

Advanced maternal age alters cardiac functional and structural adaptations to pregnancy in rats.

A significant number of pregnancies occur at advanced maternal age (>35 yr), which is a risk factor for pregnancy complications. Healthy pregnancies require massive hemodynamic adaptations, including an increased blood volume and cardiac output. There is growing evidence that these cardiovascular adaptations are impaired with age, however, little is known about maternal cardiac function with advanced age. We hypothesized that cardiac adaptations to pregnancy are impaired with advanced maternal age. Younger (4 mo; ∼early reproductive maturity in humans) and aged (9 mo; ∼35 yr in humans) pregnant Sprague-Dawley rats were assessed and compared with age-matched nonpregnant controls. Two-dimensional echocardiographic images were obtained (ultrasound biomicroscopy; under anesthesia) on gestational day 19 (term = 22 days) and compared with age-matched nonpregnant rats (n = 7-9/group). Left ventricular structure and function were assessed using short-axis images and transmitral Doppler signals. During systole, left ventricular anterior wall thickness increased with age in the nonpregnant rats, but there was no age-related difference between the pregnant groups. There were no significant pregnancy-associated differences in left ventricular wall thickness. Calculated left ventricular mass increased with age in nonpregnant rats and increased with pregnancy only in young rats. Compared with young pregnant rats, the aortic ejection time of aged pregnant rats was greater and Tei index was lower. Overall, the greater aortic ejection time and lower Tei index with age in pregnant rats suggest mildly altered cardiac adaptations to pregnancy with advanced maternal age, which may contribute to adverse outcomes in advanced maternal age pregnancies.NEW & NOTEWORTHY We demonstrated that even before the age of reproductive senescence, rats show signs of age-related alterations in cardiac structure that suggests increased cardiac work. Our data also demonstrate, using an in vivo echocardiographic approach, that advanced maternal age in a rat model is associated with altered cardiac function and structure relative to younger pregnant controls.

Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, β-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, β-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aβ peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aβ plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

Postpartum Oxytocin Treatment via the Mother Reprograms Long-Term Behavioral Disorders Induced by Early Life Stress on the Plasma and Brain Metabolome in the Rat.

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the "metabolic syndrome". We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex. We also investigated the reversal effect of postpartum carbetocin (Cbt) on these signatures, along with its impact on deficits in cognitive, social, and exploratory behavior. We found that PRS induced long-lasting changes in biomarkers of secondary bile acid metabolism in the plasma and glutathione metabolism in the frontal cortex. Cbt treatment demonstrated disease-dependent effects by reversing the metabolite alterations. The metabolomic signatures of PRS were associated with long-term cognitive and emotional alterations alongside endocrinological disturbances. Our findings represent the first evidence of how early life stress may alter the metabolomic profile in aged individuals, thereby increasing vulnerability to CNS disorders. This raises the intriguing prospect that the pharmacological activation of oxytocin receptors soon after delivery through the mother may rectify these alterations.

The mechanism by which piR-000699 targets SLC39A14 regulates ferroptosis in aging myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

Integrated Serum Pharmacochemistry and Network Pharmacological Analysis Used To Explore Possible Anti-Aging Mechanisms of the Ginsenosides

Although constitutive ginsenosides are credited with ginseng's remarkable anti-aging efficacy, the mechanism of action and bioactive components of ginsenosides are unclear. The goal of the study was to examine the effect of ginsenosides on D-galactose (D-gal)-induced aging in rats and to figure out the underlying molecular mechanism using serum pharmacochemistry and network pharmacology. Using behavioral, biochemical indexes, and histological analysis, ginsenosides were evaluated for their anti-aging effects in rats induced by D-gal, and effective ingredients absorbed in the blood were examined by ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry (UPLC-Q/TOF-MS) before being subjected to network pharmacology analysis. As well as improving spatial learning and memory skills, Ginsenosides are known to regulate malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity. In addition, it improved the ultrastructure of neurons in D-gal-induced rats' hippocampus. Seventy-four absorption components and metabolites of ginsenosides were identified in aging rat serum. According to a network pharmacology study, ginsenosides have anti-aging properties by modulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPK) signaling pathways. The potential mechanisms of the anti-aging effect of ginsenosides involve multiple components, targets, and pathways. These findings serve as a foundation for further research into the processes behind ginsenoside's anti-aging impact.

FoxO6-mediated ApoC3 upregulation promotes hepatic steatosis and hyperlipidemia in aged rats fed a high-fat diet.

FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation. In order to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts, we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO). Our findings indicate that FoxO6 triggered ApoC3-driven lipid accumulation in the livers of aged rats on an HFD and in FoxO6-Tg, consequently leading to hepatic steatosis and hyperglycemia. Conversely, the absence of FoxO6 attenuated the expression of genes involved in lipogenesis, resulting in diminished hepatic lipid accumulation and mitigated hyperlipidemia in murine models. Additionally, the upregulation of FoxO6 due to elevated glucose levels led to increased ApoC3 expression, consequently instigating cellular triglyceride mediated lipid accumulation. The transcriptional activation of FoxO6 induced by both the HFD and high glucose levels resulted in hepatic steatosis by upregulating ApoC3 and genes associated with gluconeogenesis in aged rats and liver cell cultures. Our conclusions indicate that the upregulation of ApoC3 by FoxO6 promotes the development of hyperlipidemia, hyperglycemia, and hepatic steatosis in vivo, and in vitro. Taken together, our findings underscore the significance of FoxO6 in driving hyperlipidemia and hepatic steatosis specifically under hyperglycemic states by enhancing the expression of ApoC3 in aged rats.

Young Plasma Rejuvenates Blood DNA Methylation Profile, Extends Mean Lifespan, and Improves Physical Appearance in Old Rats.

There is converging evidence that young blood conveys cells, vesicles, and molecules able to revitalize function and restore organ integrity in old individuals. We assessed the effects of young plasma on the lifespan, epigenetic age, and healthspan of old female rats. Beginning at 25.6 months of age, a group of 9 rats (group T) was intraperitoneally injected with plasma from young rats until their natural death. A group of 8 control rats of the same age received no treatment (group C). Blood samples were collected every other week. Survival curves showed that from age 26 to 30 months, none of the group T animals died, whereas the survival curve of group C rats began to decline at age 26 months. Blood DNAm age versus chronological age showed that DNAm age in young animals increased faster than chronological age, then slowed down, entering a plateau after 27 months. The DNAm age of the treated rats fell below the DNAm age of controls and, in numerical terms, remained consistently lower until natural death. When rats were grouped according to the similarities in their differential blood DNA methylation profile, samples from the treated and control rats clustered in separate groups. Analysis of promoter differential methylation in genes involved in systemic regulatory activities revealed specific GO term enrichment related to the insulin-like factors pathways as well as to cytokines and chemokines associated with immune and homeostatic functions. We conclude that young plasma therapy may constitute a natural, noninvasive intervention for epigenetic rejuvenation and health enhancement.

Cardioprotective effect of antioxidant combination therapy: A highlight on MitoQ plus alpha-lipoic acid beneficial impact on myocardial ischemia-reperfusion injury in aged rats

Objective(s): Considering the poor prognosis of ischemic heart disease and the diminished effectiveness of cardioprotective interventions in the elderly, it becomes necessary to investigate the interaction of aging with protection during myocardial ischemia/reperfusion injury (IRI). This study was conducted to assess the impact of mitoquinone (MitoQ) and alpha-lipoic acid (ALA) preconditioning on cardioprotection following IRI in aged rats. MethodsFifty aged male Wistar rats (22–24 months old) were divided into five groups including Sham, IR, and treatment groups receiving ALA and/or MitoQ. Treatment groups were received 100 mg/kg/day ALA by oral gavage and/or 10 mg/kg/day MitoQ by intraperitoneal injection for 14 consecutive days. An in vivo model of myocardial IRI was established through ligation of coronary artery for 30 min and it's reopening for 24 h. The left ventricles were removed at the end of reperfusion to assess oxidative stress indicators, mitochondrial function, and expression of mitochondrial dynamic genes. Myocardial infarct size (IS), hemodynamic parameters, and serum lactate dehydrogenase (LDH) level were also measured. ResultsCombination of MitoQ and ALA reduced oxidative stress, LDH level, and IS in aged hearts subjected to IRI. It also enhanced mitochondrial function and upregulated Mfn1, Mfn2, and Foxo1 and downregulated Drp1 and Fis1 gene expression. Co-administration of MitoQ and ALA partially restored IRI-induced hemodynamic changes to normal state. In all measured parameters, the effect of combined treatment was greater than monotherapies. ConclusionThe combination therapy of MitoQ and ALA demonstrated considerable therapeutic potential in protecting the aging heart against IRI by improving oxidative stress, mitochondrial function, and dynamics in aged rats.

Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats.

This study aimed to explore the impact of SCD Probiotics supplementation on biomolecule profiles and histopathology of ileum and colon tissues during a 30-day intermittent fasting (IF) program. Male Sprague-Dawley rats, aged 24 months, underwent 18-h daily fasting and received 3 mL (1 × 108 CFU) of SCD Probiotics. The differences in biomolecule profiles were determined using FTIR Spectroscopy and two machine learning techniques, Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM), which showed significant differences with high accuracy rates. Spectrochemical bands indicating alterations in lipid, protein and nucleic acid profiles in both tissues. The most notable changes were observed in the group subjected to both IF and SCD Probiotics, particularly in the colon. Both interventions, individually and in combination, decreased protein carbonylation levels. SCD Probiotics exerted a more substantial impact on membrane dynamics than IF alone. Additionally, both IF and SCD Probiotics were found to have protective effects on intestinal structure and stability by reducing mast cell density and levels of TNF-α and NF-κB expression in ileum and colon tissues, thus potentially mitigating age-related intestinal damage and inflammation. Furthermore, our results illustrated that while IF and SCD Probiotics individually instigate unique changes in ileum and colon tissues, their combined application yielded more substantial benefits. This study provides evidence for the synergistic potential of IF and SCD Probiotics in combating age-related intestinal alterations.