Search Results (129)

With the global aging population on the rise, identifying environmental factors that modulate immunosenescence is critical for health interventions. While urban green spaces are known to confer health benefits, the long-term effects of forest exposure on immunosenescence remain unclear. This study investigated the differential impacts of urban forest versus urban environments on immunosenescence using a D-galactose-induced murine model. Mice were assigned to urban or forest environments for 8 weeks, with serum cytokines (IL-2, IL-6, TNF-α, IFN-γ), T-cell subsets, and organ indices analyzed. Forest environments exhibited significantly higher humidity and negative air ion concentrations alongside lower noise levels compared to urban settings. Aged forest-exposed mice showed attenuated immunosenescence markers, including significantly lower IL-6 levels (p < 0.01) and improved thymic indices, suggesting urban forest environments may mitigate immune decline. These findings highlight the potential of urban forests in promoting healthy aging, advocating for their integration into urban planning. Further human studies are warranted to translate these findings into public health strategies. Full article

Background/Objectives: Lactobacillus kefiranofaciens HL1, isolated from kefir, exhibits antioxidant and anti-aging activities, defined here as improved cognitive function and reductions in oxidative stress and inflammatory markers. However, its poor milk viability limits application. This study developed a novel fermented milk by co-culturing HL1 with Lactococcus lactis subsp. cremoris APL015 (APL15) to enhance fermentation and health benefits. Methods: HL1 and APL15 were co-cultured to produce fermented milk (FM), and fermentation performance, microbial viability, texture, and syneresis were evaluated. A D-galactose-induced aging BALB/c mouse model was used to assess cognitive function, oxidative stress, inflammation, antioxidant enzyme activity, and gut microbiota after 8 weeks of oral administration. Results: FM reached pH 4.6 within 16 h, with high viable counts (~10⁹ CFU/mL) for both strains. HL1 viability and texture were maintained, with smooth consistency and low syneresis. In vivo, FM improved cognitive behavior (Y-maze, Morris water maze), reduced oxidative damage (MDA), lowered IL-1β and TNF-α, and enhanced brain SOD levels. FM-fed mice exhibited increased short-chain fatty acid producers, higher cecal butyrate, and reduced Clostridium perfringens. Conclusions: The co-cultured fermented milk effectively delivers HL1 and provides antioxidant, anti-inflammatory, and anti-aging effects in vivo, likely via gut–brain axis modulation. It shows promise as a functional food for healthy aging. Full article

Background/Objectives: Oxidative stress constitutes a principal pathophysiological mechanism driving neurodegeneration and brain aging. α-Ketoglutarate (AKG), a key intermediate of the tricarboxylic acid (TCA) cycle, has shown potential in longevity and oxidative stress resistance. However, the role of AKG in oxidative stress-induced neuronal senescence and its interaction with the mTOR signaling pathway during neuronal aging remain poorly understood, posing a key challenge for developing senescence-targeted therapies. Methods: We investigated the neuroprotective effects of AKG using H₂O₂-induced senescence in HT22 cells and a D-galactose-induced brain aging mouse model. Assessments encompassed SA-β-gal staining, EdU incorporation, mitochondrial membrane potential (JC-1), and ROS measurement. Antioxidant markers, ATP levels, and the NAD⁺/NADH ratio were also analyzed. Proteomic profiling (DIA-MS) and KEGG/GSEA enrichment analyses were employed to identify AKG-responsive signaling pathways, and Western blotting validated changes in mTOR signaling and downstream effectors. Results: AKG significantly alleviated H₂O₂-induced senescence in HT22 cells, evidenced by enhanced cell viability, reduced ROS level, restored mitochondrial function, and downregulated p53/p21 expression. In vivo, AKG administration improved cognitive deficits and vestibulomotor dysfunction while ameliorating brain oxidative damage in aging mice. Proteomics revealed mTOR signaling pathways as key targets for AKG’s anti-aging activity. Mechanistically, AKG suppressed mTOR phosphorylation and activated ULK1, suggesting modulation of autophagy and metabolic homeostasis. These effects were accompanied by enhanced antioxidant enzyme activities and improved redox homeostasis. Conclusions: Our study demonstrates that AKG mitigates oxidative stress-induced neuronal senescence through suppression of the mTOR pathway and enhancement of mitochondrial and antioxidant function. These findings highlight AKG as a metabolic intervention candidate for age-related neurodegenerative diseases. Full article

Background/Objectives: The aim of this study was to investigate the role and potential mechanism of deer antler peptides (DAP) in D-galactose (D-gal)-induced brain injury. Methods: In the in vivo study, C57BL/6J mice were intraperitoneally injected with 400 mg/kg D-gal and gavaged with DAP (50 and 200 mg/kg) for 5 weeks. In vitro studies, D-gal (30 μg/mL) induced senescent BV2 cells were used for further research. Results: DAP increased the expression of BDNF and VEGF in the brain tissue of aging mice, reduced the levels of oxidative stress and inflammatory factors in serum, and decreased the pathological damage of brain tissue. In vitro, DAP promoted the proliferation of D-gal-induced senescent BV2 cells, reduced ROS level, and inhibited the release of IL-1β, IL-6 and TNF-α. In addition, DAP significantly reduced the protein expressions of TLR4 and MyD88, and inhibited the phosphorylation of NF-κB. Conclusions: DAP can inhibit the TLR4/MyD88/NF-κB signaling pathway, reduce oxidative stress and inflammation, and promote neovascularization. This indicates the therapeutic potential of DAP as a natural bioactive substance in preventing aging-related brain injury. Full article

Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used in vitro model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular aging and rejuvenation, placental derivatives have a well-established history in anti-aging skincare and therapy. However, trophoblast-derived extracellular vesicle (TEV) effects on D-galactose-induced premature aging in keratinocytes have not been investigated yet. TEV pretreatment for 24 h enhanced cellular resilience against D-galactose-induced stress, judging by the downregulated expression of senescence- and stress-associated markers (p19 and p21, HIF-1α, mTOR), and reduced production of reactive oxygen species and DNA damage. Additionally, TEV pretreatment enhanced keratinocyte proliferation and integrin-β1 subunit expression upon D-galactose exposure, most likely contributing to more efficient wound closure. In conclusion, this study underscores the potential of TEVs to modify expression of stress- and senescence-related proteins in keratinocytes and improve their wound healing properties. Their regenerative and protective characteristics position TEVs as promising candidates for developing innovative procedures to address skin conditions related to premature aging. Full article

Background/Objectives: Dihydromyricetin (DHM), a flavonoid with abundant natural sources, potent bioactivity, and high safety, holds promise for translational applications, particularly in mitigating skin aging. However, its role and underlying mechanisms in counteracting skin aging induced by advanced glycation end products (AGEs) remain unclear. Methods: Eight-week-old male Sprague-Dawley (SD) rats were subcutaneously injected with 500 mg/kg D-galactose and administered DHM via gavage for 11 weeks. Additionally, senescent human skin fibroblasts (HFF-1) induced by AGEs were used for further investigation. Results: DHM treatment significantly alleviated D-galactose-induced skin aging in rats, with the most pronounced effects observed in the moderate-dose group (100 mg/kg). Compared to the aging group, DHM enhanced skin elasticity and preserved collagen levels. Moreover, DHM promoted cell proliferation in the skin. Further studies on AGE-induced senescent fibroblasts revealed that DHM markedly reduced multiple senescence-associated markers and stimulated cell proliferation by approximately a 1.5-fold increase. Transcriptomic analysis indicated that DHM upregulated genes related to the cell cycle and DNA repair while suppressing AGE-RAGE signaling and its downstream pathways. Notably, DHM downregulated AGER, the gene encoding the receptor for AGEs (RAGE). Molecular docking analysis demonstrated that DHM shares a binding site with other known RAGE inhibitors. Surface plasmon resonance (SPR) analysis further confirmed the high binding affinity of DHM to RAGE (K_D = 28.7 μM), which was stronger and more stable than that of FPS-ZM1 (K_D = 40.7 μM). Conclusions: DHM may attenuate glycation-induced skin aging in rats by functioning as a RAGE inhibitor, thereby suppressing AGE-RAGE signaling, delaying cellular senescence, and promoting cell proliferation. Full article

As the global elderly population is rising, concerns about cognitive decline and memory loss are becoming urgent. This study evaluated the potential of sea cucumber hydrolysates (SCH) from Stichopus japonicus in alleviating cognitive deficits using a D-galactose-induced murine aging model. The effects of SCH on behavior, hippocampal morphology, gut microbiota, hippocampal cholinergic system, brain-derived neurotrophic factor (BDNF) signaling, and neuroinflammatory pathways were investigated. Results showed that SCH ameliorated learning and memory deficits and reduced neuronal damage in aging mice. SCH also modulated gut microbiota, along with increased fecal short-chain fatty acids levels. Functional prediction revealed that alterations in gut microbiota were related to signal transduction. Further, SCH enhanced hippocampal cholinergic function through elevating acetylcholine (ACh) levels and inhibiting acetylcholinesterase (AChE) activity and activated BDNF signaling, consistent with predictions of gut microbiota function. Restoration of cholinergic homeostasis and transmission of the BDNF pathway might contribute to the inhibition of hippocampal neuroinflammation via suppressing microglial activation and the nuclear factor kappa-B (NF-κB) pathway. In summary, SCH attenuated cognitive deficits through suppressing neuroinflammation, which might be correlated with the signal transduction caused by regulating gut microbiota. Further validation will be conducted through microbiota depletion and fecal microbiota transplantation. These findings suggest that SCH is a promising functional component for counteracting aging-related cognitive deficits. Full article

This study introduces a novel recombinant humanised collagen (DuCol) developed through codon optimisation and prokaryotic soluble expression, exhibiting exceptional biocompatibility and bioactivity. Structural integrity was confirmed via RP-HPLC, SEM, and CD spectroscopy. In vitro evaluations revealed DuCol’s dose-dependent enhancement of NIH-3T3 fibroblast proliferation, adhesion, and migration. In a D-galactose-induced ageing rat model, subcutaneous implantation of DuCol showcased time-dependent anti-ageing effects. Early-stage intervention (30 days post-injection) markedly upregulated COL1A1 expression through the TGF-β/Smad3 pathway activation, outperforming poly-l-lactic acid (PLLA) in collagen deposition. Histological analysis revealed 23.4% greater dermal thickness in DuCol-treated groups compared to PLLA at 90 days. While PLLA exhibited sustained collagen stimulation beyond 90 days, DuCol exhibited superior early-phase efficacy (p < 0.001) with comparable safety profiles (no inflammatory response observed through 180-day monitoring). The combinatorial PLLA/DuCol (P&C) formulation synergistically enhanced dermal regeneration, achieving a 31.7% thicker collagen matrix than monotherapy groups. These results underscore the potential of DuCol as a novel implantable filler material for skin repair and regeneration. Full article

Aging-related diseases have become a global health issue, with the escalating aging population leading to an increased disease incidence, placing immense pressure on individual health and society. Lycium ruthenicum Murray anthocyanins are hailed as the “Black Pearl of the Desert”. Anthocyanins are potent natural antioxidants that can combat oxidation, reduce inflammation, prevent cardiovascular diseases, protect the liver, and inhibit tumor cell growth. As individuals age, the accumulation of free radicals in the body accelerates aging. Antioxidants mitigate aging by neutralizing free radicals, and the anthocyanins in Lycium ruthenicum Murray effectively reduce oxidative damage, activate the antioxidant enzyme system, and enhance the body’s antioxidant capacity, thereby slowing the aging process. This study investigated Lycium ruthenicum Murray Anthocyanins’ (LRAs) anti-aging mechanisms using D-galactose-induced H9c2 cells and H₂O₂-treated zebrafish. LRAs increased survival rates (30.47% cells, 20.02% zebrafish), reduced ROS, Sa-β-gal, and apoptosis markers, while boosting antioxidant enzymes (SOD, CAT, GSH) and lowering MDA. It upregulated Bcl-2/SIRT1 and downregulated Bax/P53/P21/NF-κB/MAPK/TNF-α genes, with protein-level SIRT1 activation and P53/P21 suppression. The transcriptome analysis revealed a significant reduction in aging-related gene expression levels. The results demonstrated that LRAs mitigate aging through SIRT1/P53-mediated oxidative stress inhibition and apoptosis reduction, suggesting their therapeutic potential for age-related disorders. Full article

Age-related hearing loss (ARHL) is a highly prevalent, burdensome sensorineural hearing loss closely associated with impaired autophagic influx. Our previous studies revealed that neuritin, a neurotrophic factor primarily expressed in the central nervous system, could alleviate drug-induced damages in hair cells (HCs) and spiral ganglion neurons. However, its effects on ARHL and whether these effects are closely related to autophagy remain unclear. Using the Nrn1 knock-in mice and cultured cochlear basilar membrane (CBM) of the neonatal mouse, we show that neuritin could restore aging-associated hearing loss and alleviate senescence-associated damage in the cochlea. Overexpression of neuritin in support cells (SCs) alleviates the loss of cochlear HCs and nerve fibers, reducing the damage to spiral ganglion neurons and the shifts in ABR’s high-frequency threshold. Furthermore, conditional overexpression of neuritin in SCs improves autophagic influx by upregulating the expression of microtubule-associated protein 1 light chain 3 type B (LCB3) protein and downregulating the expression of p21 protein. In cultured neonatal mouse CBM, neuritin administration significantly inhibits D-galactose-induced HC loss, cellular apoptosis, and ROS production and promotes autophagic influx. These effects were weakened when the autophagy inhibitor 3-MA was added. In summary, our results confirm the therapeutic potential of neuritin treatment for ARHL. Full article

This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP’s effects, highlighting TLR4, IL-1β, and Mmp9 as core regulatory genes through protein–protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity. Full article

D-galactose (d-gal) plays numerous roles in the organism as an energy-providing nutrient and also an important constituent of the complex glycoconjugates. However, excessive amounts of d-gal activate alternative metabolic pathways that can lead to the development of a pro-oxidative environment. This feature is used in numerous aging studies which implied intraperitoneal (i.p.) or subcutaneous (s.c.) administration of d-gal for a prolonged time. The present study aims to investigate the systemic effects of orally administered d-gal (200 mg/kg and 500 mg/kg, dissolved in tap water, for 6 weeks) by analyzing oxidative stress parameters in the liver, kidney, and heart. For comparison with natural aging, the effects were studied in rats aged 12, 18, 24, and 30 months. In addition, histopathologic analyzes and serum biochemical measurements were performed to investigate the potential structural and functional organ damage induced by d-gal administration. Our findings show that chronic oral administration of d-gal induces oxidative stress in rat organs and mimics some aspects of natural aging similar to those of 30-month-old rats. Consistent with its primary role in galactose metabolism, the liver exhibited the most pronounced oxidative damage. However, despite the increased oxidative stress, only minor histopathological changes were observed, while organ function remained largely unaffected. Oral intake of d-gal was found to have milder effects compared to i.p. or s.c. injections, suggesting that this model may induce some features of natural aging but without overt organ dysfunction. Full article

Background: Skeletal muscle wasting is commonly observed in aging, immobility, and chronic diseases. In pathological conditions, the impairment of skeletal muscle and immune system often occurs simultaneously. Recent studies have highlighted the initiative role of skeletal muscle in interactions with immune cells. However, the impact of skeletal muscle wasting on macrophage inflammatory responses remains poorly understood. Methods: To investigate the effect of atrophic myotubes on the inflammatory response of macrophages, we established two in vitro models to induce myotube atrophy: one induced by D-galactose and the other by starvation. Conditioned medium (CM) from normal and atrophic myotubes were collected and administered to bone marrow-derived macrophages (BMDMs) from mice. Subsequently, lipopolysaccharide (LPS) stimulation was applied, and the expression of inflammatory cytokines was measured via RT-qPCR. Results: Both D-galactose and starvation treatments reduced myotube diameter and upregulated muscle atrophy-related gene expression. CM from both atrophic myotubes models augmented the gene expression of pro-inflammatory factors in BMDMs following LPS stimulation, including Il6, Il1b, and Nfkb1. Notably, CM from starvation-induced atrophic myotubes also enhanced Il12b, Tnf, and Nos2 expression in BMDMs after stimulation, a response not observed in D-galactose-induced atrophic myotubes. Conclusions: These findings suggest that CM from atrophic myotubes enhanced the expression of LPS-induced pro-inflammatory mediators in macrophages. Full article

Background: Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven by oxidative stress. This oxidative stress is particularly detrimental to the testes, where it causes degeneration, reduced testosterone levels, and compromised fertility. D-galactose (D-gal) is commonly used to model aging as it induces oxidative stress, mimicking age-related cellular and molecular damage. Testicular aging is of significant concern due to its implications for reproductive health and hormonal balance. This research examines the protection by thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against D-galactose (D-gal)-induced aging in rat testes, focusing on biochemical, histological, and molecular changes. Aging, which is driven largely by oxidative stress, leads to significant testicular degeneration, reducing fertility. D-gal is widely used to model aging due to its ability to induce oxidative stress and mimic age-related damage. TQ, a bioactive ingredient of Nigella sativa, has earned a reputation for its anti-inflammatory, anti-apoptotic, and antioxidant characteristics, but its therapeutic application is limited by its poor bioavailability. Methods: Thymoquinone was loaded into chitosan nanoparticles (NCPs) to enhance its efficacy, and this was hypothesized to improve its stability and bioavailability. Four groups of male Wistar rats participated in the study: one for the control, one for D-gal, one for D-gal + TQ, and the last one for D-gal + NCP. Results: The results exhibited that D-gal substantially increased oxidative injury, reduced testosterone levels, and caused testicular damage. Treatment with TQ and NCPs significantly reduced oxidative stress, improved antioxidant enzyme levels, and restored testosterone levels, with NCPs showing a stronger protective effect than TQ alone. A histological analysis confirmed that NCPs better preserved testicular structure and function. Additionally, the NCP treatment upregulated the expression of key genes of oxidative stress resistance, mitochondrial function, and reproductive health, including SIRT1, FOXO3a, and TERT. Conclusions: The findings suggest that NCPs offer enhanced protection against aging-related testicular damage compared with TQ alone, which is likely due to the improved bioavailability and stability provided by the nanoparticle delivery system. This research emphasizes the potential of NCPs as a more effective therapeutic strategy for mitigating oxidative stress and age-related reproductive dysfunction. Future research should further explore the mechanisms underlying these protective effects. Full article

Background/Objectives: This study aimed to evaluate the renal protective effects of black rice anthocyanins (BRAs) against renal injury in mice induced by D-galactose (D-gal). Methods: The renal aging mouse model was established by thirteen consecutive weeks of subcutaneous injections of D-gal. The serum levels of urea nitrogen (BUN), creatinine (CRE), uric acid (UA), antioxidant enzymes (e.g., GSH-Px and SOD), and total antioxidant capacity (T-AOC), as well as the contents of inflammatory factors (IL-1β, IL-6, and TNF-α) in kidney tissues were evaluated. Additionally, the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins was examined. Results: BRA treatment significantly reduced serum levels of BUN, and CRE increased the concentrations of antioxidant enzymes and total antioxidant capacity in renal tissues, and reduced the levels of inflammatory factors. Furthermore, BRAs restored the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins to normal levels and promoted the recovery of the renal tissue architecture. Conclusions: It was demonstrated that BRAs could potentially prevent and protect against kidney injury by modulating the Nrf2 and NF-κB signaling pathways, attenuating oxidative stress and inflammatory responses, and modulating the gut microflora. These findings provide a scientific basis for the application of BRAs as a natural bioactive substance in the field of nephroprotection, especially against the renal degeneration that accompanies the aging process. Full article