Search Results (117)

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Background/Objectives: Nutraceuticals containing milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are purported to abate age-related metabolic dysfunction due to their richness in milk sphingolipids. As such, nutraceuticals offer a compelling strategy to improve metabolic health through dietary means, especially for elderly persons who are unable to adhere to common therapeutic interventions. To address this, we examined the effects of supplementing aged sedentary rats with an MFGM/EV-rich concentrate. Methods/Results: In a 25-week study, 89-week-old male rats received either a milk sphingolipid-rich MFGM/EV concentrate or a control supplement. Analysis of metabolic health using a battery of tests, including MS^ALL lipidomics of plasma, liver, and other peripheral tissues, revealed that MFGM/EV supplementation promotes accretion of unique sphingolipid signatures, ameliorates ceramide biomarkers predictive of cardiovascular death, and has a general lipid-lowering effect. At the functional level, we find that these health-promoting effects are linked to increased lipoprotein particle turnover, showcased by reduced levels of triglyceride-rich particles, as well as a metabolically healthier liver, assessed using whole-body lipidomic flux analysis. Conclusions: Altogether, our work unveils that MFGM/EV-containing food holds a potential for ameliorating age-related metabolic dysfunction in elderly individuals. Full article

Intracerebral hemorrhage (ICH), a severe stroke subtype common in the elderly, often results in high morbidity and mortality, with limited treatment options for long-term recovery. While glial scar formation is increasingly recognized as key to central nervous system (CNS) repair, its role and characteristics in the aging brain post-ICH remain unclear. This study investigated glial scar formation after ICH (100 μL autologous blood injected into the right basal ganglia model) in aged Fischer 344 rats and assessed the effects of deferoxamine (DFX) treatment. Histological and immunohistochemical analyses were conducted on days 7, 28, and 60 post-ICH using cell-specific and iron-related markers, with DFX administered at 100 mg/kg daily for 14 days in separate groups. Over time, the lesion core showed increased hemosiderin accumulation and astrogliosis. By day 60, the area of astrogliosis corresponded to an area with persistent neuronal loss (DARPP-32-negative). Glial composition shifted from microglia dominance on day 28 to astrocyte predominance by day 60. DFX treatment reduced iron deposition, astrogliosis, and DARPP-32-negative regions while enhancing oligodendrocyte presence. Iron-related markers (HO-1, ferritin, Perls’ staining) and PDGFRβ-positive fibrotic cells were concentrated in the scar core. These findings provide novel insights into scar formation after ICH in aged rats and suggest DFX as a potential therapy to improve outcomes in elderly stroke patients. Full article

Background: Lung cancer represents a significant health concern, particularly among the elderly population. With global life expectancy increasing, the number of very elderly patients is rising. Robotic-assisted thoracic surgery (RATS) offers potential advantages over both traditional and video-assisted thoracoscopic surgery (VATS). This study aims to evaluate the feasibility and safety of RATS in very elderly patients (VEP) diagnosed with lung cancer. Methods: This retrospective study included patients who underwent major lung resections using RATS between 2015 and 2022 at two specialized centers. Patients were divided into very elderly patients (VEP, ≥80 years) and non-elderly patients (NEP, <80 years). Demographic, clinical, and surgical data were analyzed. Propensity score matching (PSM) at a 1:3 ratio was performed using clinically relevant variables that were significantly different at baseline to balance the two groups. Results: This study included 340 patients: 28 VEP and 312 NEP. Before PSM, VEP had higher ASA scores, more advanced disease stages, and increased comorbidities. Despite these differences, postoperative outcomes were comparable. Complications occurred in 42.9% of VEP and 29.8% of NEP (p = 0.16), but grade III complications were observed in 14.3% of VEP and 6.4% of NEP (p = 0.12), and grade IV complications were observed in 0% of VEP and 0.9% of NEP (p = not estimable). The mean hospital stay was 4 days in both groups (p = 0.99). Even after PSM (26 VEP vs. 71 NEP), complications, hospital stay, and 90-day mortality (3.9% in VEP, 0% in NEP) were similar. Multivariable analysis identified reduced FEV1 as a predictor of complications, while pathological stage I and lobectomy were associated with a decreased risk of complications, both before and after PSM. Conclusions: RATS is a safe and feasible option for selected very elderly patients with lung cancer, yielding outcomes comparable to younger patients. Full article

As the proportion of the elderly population increases, there is an urgent need for anti-aging technologies. Since the skin is the most visibly aging organ in the human body, it is crucial to develop active ingredients to slow down skin aging. Currently, identified anti-aging active substances include antioxidants, retinoids, peptides, growth factors, and compounds derived from biofermentation. However, they have limitations such as poor stability, low transdermal permeability, skin irritation, high effective concentrations, slow onset of efficacy, single-action mechanisms, and high production costs. These limitations highlight the necessity of developing new anti-aging technologies that are multifunctional and cause low irritation. This study aimed to investigate the anti-aging effects and mechanisms of fructosazine (FZ) and deoxyfructosazine (DOF) on the skin as well as their potential applications in skincare. The methods included ELISA tests to assess the viability of human dermal fibroblast (NHDF) cells and related factors, and monitoring in Sprague-Dawley (SD) rats. The results showed that FZ promoted cell viability. Both FZ and DOF enhanced the secretion of type I collagen (Col I) and hyaluronic acid (HA), inhibited matrix metalloproteinase-1 (MMP-1), boosted catalase (CAT), and reduced malondialdehyde (MDA), reactive oxygen species (ROS), and β-galactosidase. They also nourished the epidermis and increased fiber content. In conclusion, FZ and DOF can stimulate the production of anti-aging substances, exhibit antioxidant activity, and have potential in skincare. Full article

Osteoarthritis (OA), the most common degenerative pathology of the joints, affects mainly elderly people, and it is one of the most important factors causing disability. This study aimed to assess the effect of Juglans regia L. on rats with collagenase-induced knee osteoarthritis comparative with groups with the same disease treated with ellagic acid (EA), indomethacin as positive control and vehicle as negative control. After 2 and 4 weeks of treatment, blood samples were collected in order to evaluate the oxidative stress and inflammation, as well as RANKL and hydroxyproline levels. The results showed that EA improved the systemic antioxidant defense (p < 0.05), decreased the interleukin-6 (IL-6) secretion (p < 0 < 0.05) and RANKL levels (p < 0.01 and p < 0.001) at the same time enhancing hydroxyproline values, particularly after 2 weeks of treatment (p < 0.01). JR extract especially maintained low values of RANKL (p < 0.05) and hydroxyproline levels (p < 0.05), indicating a partial chondroprotective effect compared to EA. In conclusion, the use of EA and JR extract can improve some parameters of bone regeneration in experimental osteoarthritis, suggesting beneficial effects in articular inflammatory diseases. However, further studies are necessary to establish the optimum dose and time of treatment with both compounds in order to obtain optimal therapeutic results. Full article

Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of TMAO help proteins preserve their folding, high levels of this metabolite are harmful and promote oxidative stress, inflammation, and atherosclerosis. In humans, elevated levels of circulating TMAO predispose individuals to cardiovascular diseases and chronic kidney disease and increase mortality risk, especially in the elderly. How TMAO exerts its negative effects has been only partially elucidated. In hypertensive rats, the eNOS substrate L-arginine and Taurisolo^®, a nutraceutical endowed with TMAO-reducing activity, act synergistically to reduce arterial blood pressure. Here, we investigate the molecular mechanisms underpinning this synergism and prove that TMAO, the target of Taurisolo^®, acts as direct inhibitor of endothelial nitric oxide synthase (eNOS) and competes with L-arginine at its catalytic site, ultimately inhibiting NO production and acetylcholine (Ach)-induced relaxation in murine aortas. Full article

Background: Lower urinary tract symptoms (LUTS) due to prostate hyperplasia are the most frequent urological symptoms in elderly men. Current pharmacological treatments for LUTS and benign prostatic hyperplasia (BPH) are widely used in clinical practice; however, adverse effects associated with these drugs have been reported for sexual dysfunction and orthostatic hypotension. Prunella vulgaris (PV) is a medicinal herb that has a long history of use. This study aimed to address this gap by investigating the relaxant activity of PV extract (PVE) on rat prostate smooth muscle ex vivo and evaluating intravesical cystometry for its potential. Methods and Results: Ten male Sprague Dawley (SD) rats were used to study the relaxant efficacy of PVE and its constituents in isometric contraction ex vivo. Thirty-six SD rats were randomly assigned to six groups of six animals (n = 6) and administered testosterone propionate (TP; 3 mg/kg) daily for 4 weeks to induce BPH. Groups of BPH rats were treated with or without PVE (30, 60, or 90 mg/kg) via oral gavage. At the end of the experiments, the animals were subjected to intravesical pressure under urethane anesthesia. After successful cystometric recording, rats were euthanized with carbon dioxide. Prostate and bladder tissues were harvested and processed for histological and biochemical analysis. The results demonstrated that PVE exerted relaxant effects on prostatic smooth muscle in a concentration-dependent manner, mediated by nitric oxide and potassium channels, without antagonizing adrenergic receptors. Additionally, intravesical cystometry in SD rats treated with oral gavage of PVE for 4 weeks showed a significant improvement in voiding abnormalities. Conclusions: These findings suggest the potential of PV and its compounds as a therapeutic strategy to improve LUTS associated with BPH. Full article

Background: Middle-aged and elderly individuals may experience detrimental health effects due to ischemic stroke (IS). The inflammatory response triggered during IS exacerbates neuronal damage, becoming a barrier to effective IS treatment and leading to poor patient prognosis. Nevertheless, the specific role of microglia in the inflammatory response triggered by IS remains mostly unclear. The primary target of this investigation is to study the neuroinflammatory impact of lycorine (LYC) during the IS process. Our objective is to evaluate whether LYC deploys its anti-inflammatory effect with modulation of the NF-κB signaling pathway, thereby reducing IS symptoms. Methods: In this research, BV-2 cells were pre-treated with LYC for 24 h before LPS was added to induce inflammation. Results: It has been discovered that LYC suppresses BV-2 cell polarization and reduces the levels of inflammatory cytokines (IL-1β, IL-6, TNF-α), showing its potential anti-inflammatory effects in vitro. Furthermore, IκBα and p65 play crucial roles in regulating the inflammatory response within the NF-κB signaling pathway. Mechanistic exploration indicates that LYC can activate the expression of IκBα in LPS-induced BV-2 cells. IκBα inhibits NF-κB by binding to its p65 subunit, sequestering it in the cytoplasm and preventing its translocation to the nucleus, thereby inhibiting inflammation. Additionally, p65 is a key transcription factor for pro-inflammatory genes, and its downregulation leads to decreased transcriptional activity of these genes. The combined effect of increased IκBα and decreased p65 results in significantly reduced NF-κB activity, thereby alleviating the inflammatory response. Meanwhile, in vivo studies indicate that LYC pre-treatment significantly reduces the infarct size caused by middle cerebral artery occlusion (MCAO) in rats. The assessment of cerebral infarction volume, neurological scores, brain edema rate and inflammation levels in MCAO rats pre-treated with LYC indicates positive therapeutic effects. Conclusions: In summary, our research indicates that LYC pre-treatment has significant anti-inflammatory effects by attenuating inflammation levels through NF-κB inhibition, which contributes to potential therapeutic benefits in ischemic stroke (IS) and may improve disease prognosis. LYC may serve as an adjunctive clinical pre-treatment for IS, which has to be confirmed by clinical trials in the future. Full article

Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), a perennial herb of the Cucurbitaceae family, has been used since the Ming dynasty as a medicinal material to treat various ailments, such as rheumatism, liver disease, and diabetes. In this study, we investigated the anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin (AP)) and its derivatives, damulin A (DA) and damulin B (DB), using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems. Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001). In addition, cartilage thickness and chondrocytes were reduced in the DMM group, but were restored in the AP-administered group. Furthermore, the von Frey analysis results showed that the pain threshold of the DMM group was considerably low (54.5 g at 8 weeks), whereas that of the AP group was dose-dependently increased (65.5, 69.5, 70.3, and 71.8 at 8 weeks for 30, 50, 100, and 200 mg/kg, respectively). In vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. Collectively, these results suggest that AP is a potential therapeutic agent for mitigating OA progression and chondroprotection. Full article

Deterioration in muscle mass, strength, and physical performance due to conditions such as sarcopenia can affect daily activities and quality of life in the elderly. Exercise and mesenchymal stem cells (MSCs) are potential therapies for sarcopenia. This study evaluates the combined effects of exercise and adipose-derived MSCs (ADMSCs) in aged rats with sarcopenia. Eighteen-month-old rats were randomly divided into four groups: control, exercise (Ex), ADMSCs injection (MSC), and ADMSCs injection with exercise (MSC + Ex). Gastrocnemius (GCM) muscle mass increased in the Ex, MSC, and MSC + Ex groups compared to the control group. Although the mean CSA did not differ significantly between the groups, the size distribution of myofibers shifted toward larger sizes in the Ex and MSC + Ex groups. The MSC + Ex group performed best in functional tests, including the rotarod and hot plate tests. The protein expression levels of tumor necrosis factor (TNF) and the p-AMP-activated protein kinase (AMPK)/AMPK ratio in the GCM muscle were the lowest in the MSC + Ex group. This study demonstrates that combining exercise and ADMSC interventions was the most effective treatment for aged sarcopenic rats, suggesting a potential synergistic approach for sarcopenia treatment. Full article

Stroke, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease are some of the conditions that can lead to neuromotor disabilities requiring rehabilitation. To address the socio-economic burden that is amplified by the rapidly increasing elderly population, traditional rehabilitation techniques have recently been complemented by technological advancements, particularly Robot-Assisted Therapy (RAT). RAT enhances motor learning by improving both accuracy and consistency. This study proposes an innovative rehabilitation system that combines serious gaming and augmented reality (AR) with the LegUp parallel robot, developed for the spatial rehabilitation of the hip, knee, and ankle in bed-ridden patients. The system aims to improve patient outcomes and actively involve patients in their therapy. Electro-goniometers and a HoloLens 2 device are used to provide immediate feedback about the position of the patient’s joints, forming the basis of an interactive game in which the patient moves their leg to reach various targets. Two game modes were developed, each targeting different aspects of neuromotor rehabilitation, such as coordination, strength, and flexibility. Preliminary findings suggest that combining RAT with augmented reality-based serious gaming can increase patient motivation and engagement. Furthermore, the personalized and interactive nature of the therapy holds the potential to improve rehabilitation outcomes by fostering sustained engagement and effort. Full article

Background/Objectives: Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal glands, plays a key role in various physiological processes, including bone health. Its age-related decline is linked to reduced bone density, though the mechanisms by which DHEA affects bone metabolism remain complex. This review summarises the diverse effects of DHEA on bone metabolism and density, highlighting its therapeutic potential; Methods: A literature search on the effects of DHEA on bone-related parameters was conducted from PubMed and Scopus using a specific search string, and after removing duplicates and irrelevant articles, 36 relevant full-text studies were included; Results: DHEA promotes osteoblast differentiation and proliferation, regulates the RANKL/OPG ratio, and inhibits osteoclastogenesis and bone resorption. Its osteogenic effects are mediated through multiple signalling pathways. In ovariectomised rat models, DHEA enhances trabecular bone volume, stimulates osteoblast proliferation, and increases oestradiol production and aromatase activity. In elderly individuals with low androgen levels, DHEA supplementation increases sulphated DHEA and oestradiol levels and improves bone mineral density, particularly in the ultra-distal radius of women and the femoral neck of men. However, the clinical use of DHEA remains debated due to inconsistent study results. Its effects on bone health may vary based on factors such as age, gender, and health conditions, emphasising the need for further research to clarify its mechanisms and optimise its use; Conclusions: In conclusion, while DHEA shows potential as a modulator of bone health, comprehensive clinical trials are required to assess its efficacy and safety, particularly in at-risk populations. Full article

Background/Objectives: Sarcopenia, a condition marked by muscle wasting due to aging or inactivity, severely affects older populations. We previously showed that pasteurized Akkermansia muciniphila HB05 (HB05P), sourced from the breast milk of healthy Korean women, could mitigate muscle wasting in a dexamethasone-induced rat model. Here, we explored whether the oral administration of HB05P can enhance muscle strength and functionality in elderly individuals. Our objective was to determine if HB05P supplementation could benefit muscle performance in aging adults. Methods: We conducted a 12-week, double-blind, placebo-controlled clinical trial involving 100 individuals aged 60 and above, randomly assigned to receive either HB05P (1.0 × 10¹⁰ cells/day) or a placebo. Results: The HB05P group showed significant improvements in peak torque and peak torque per body weight of the left leg extensor muscles compared to the placebo group (p = 0.0103 and p = 0.0052). Furthermore, HB05P notably elevated follistatin levels, which counteract myostatin, relative to the placebo group (p = 0.0063). No notable safety concerns arose between the groups. Conclusions: HB05P is a promising postbiotic derived from Akkermansia muciniphila that may enhance muscle strength and be used as a safe postbiotic ingredient of Akkermansia muciniphila to improve muscle health. Full article

Sepsis-associated acute kidney injury (SA-AKI) presents a severe challenge in the elderly due to increasing incidence, high mortality, and the lack of specific effective treatments. Exploring novel and secure preventive and/or therapeutic approaches is critical and urgent. Berberine (BBR), an isoquinoline alkaloid with anti-inflammatory, antioxidant, and immunomodulatory properties, has shown beneficial effects in various kidney diseases. This study examined whether BBR could protect against SA-AKI in aged rats. Sepsis was induced in 26-month-old male Wistar rats by cecal ligation and puncture (CLP), either with or without BBR pretreatment. CLP induction led to SA-AKI, as indicated by elevated serum levels of malondialdehyde, tumor necrosis factor-alpha, urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL), along with histopathological features of kidney damage. Key indicators of kidney oxidative stress, mitochondrial dysfunction, apoptosis, and activations of the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling, including the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome pathway, were also elevated following CLP induction. BBR pretreatment substantially mitigated these adverse effects, suggesting that it protects against SA-AKI in aged rats by reducing oxidative stress, preserving mitochondrial integrity, and inhibiting key inflammatory pathways. These findings highlight the potential of BBR as a therapeutic agent for managing SA-AKI in elderly populations. Full article