Search Results (986)

Background and Objectives: The aim of this study was to investigate the changes in the SIRT family, the effects of sirtuins on kidney graft function, and their potential as biomarkers in patients who develop rejection after kidney transplantation. Materials and Methods: Blood samples were collected from 45 kidney transplant patients before and after rejection. Some of these patients experienced T-cell-mediated early rejection (TCMR), while others presented antibody-mediated late rejection (ABMR). The mRNA expression levels of SIRT-1, SIRT-3, and SIRT-7 were measured via real-time PCR, while the protein levels of SIRT-1, SIRT-2, SIRT-3, SIRT-5, and SIRT-7 were assessed using ELISA. Patients were grouped based on rejection type and histological characteristics. Statistical analyses were performed using SPSS software (V23). Results: The mean age of the patient group was 42.22, while the control group had a mean age of 35.23 (p = 0.002). SIRT-1, SIRT-3, and SIRT-7 levels were significantly higher in patients with rejection (p < 0.001). In patients with late-stage rejection, SIRT-3 was found to be associated with interstitial fibrosis and C4d accumulation. SIRT-7 levels showed a weak correlation with potassium levels (p = 0.014). Conclusions: Our findings demonstrate significant changes in the SIRT family during both early- and late-stage rejection processes. Particularly, the role of SIRT-3 in the late stage is highlighted, suggesting the potential use of this gene as a biomarker for managing rejection processes. These findings could provide valuable insights for developing treatment strategies in organ transplantation. Full article

Epigenetic modulation plays a crucial role in neuroprotection by regulating cellular responses to stress, inflammation, and oxidative damage, particularly in neurodegenerative diseases. Recognizing the therapeutic potential of epigenetic regulators, this study investigated the synergistic neuroprotective effects of curcumin-enriched turmeric extract combined with L-ascorbic acid, focusing on its modulation of epigenetic pathways in oxidative stress-induced neuronal damage. SH-SY5Y neuronal cells were treated with the combination at 20 and 40 µg/mL, and subsequently exposed to 200 µM hydrogen peroxide (H₂O₂) to induce oxidative stress. Cell viability was assessed using the MTT assay, while neuroprotective mechanisms were evaluated by analyzing the markers of epigenetic modulation, oxidative stress, inflammation, and apoptosis. The combination significantly enhanced cell viability, upregulated sirtuin-1 (SIRT1), and reduced DNA methyltransferase 1 (DNMT1) expression, indicating effective epigenetic modulation. Enhanced antioxidant defenses were observed, as evidenced by increased activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), along with decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels, alleviating oxidative stress. Additionally, it suppressed nuclear factor kappa B (NF-κB) activity and its downstream mediator interleukin-6 (IL-6), thereby mitigating inflammation. The treatment also increased anti-apoptotic Bcl-2 expression while reducing pro-apoptotic markers, including caspase-3 and caspase-9, suggesting inhibition of the intrinsic apoptotic pathway. These findings highlight the novel neuroprotective effects of this combination, demonstrating its ability to modulate epigenetic pathways while reducing oxidative stress, suppressing inflammation, and preventing undesired apoptosis. Its multifaceted neuroprotective properties make it a promising functional ingredient in functional foods for neurodegenerative disease intervention. However, further investigations, including animal studies and clinical trials, are essential to evaluate its safety and therapeutic potential. Full article

(1) Background: this study investigates the short-term effects of coenzyme Q10 (CoQ10) on mitochondrial respiration, fatty acid metabolism, oxidative stress gene expression, and sirtuin activity in young (passage 5, P5) and aged (passage 16, P16) mesenchymal stem cells (MSCs). (2) Methods: Mitochondrial respiration was assessed by measuring oxygen consumption after 24 h of treatment. Gas chromatography–mass spectrometry (GC-MS) analysis assessed cellular fatty acid methyl ester profiles. Quantitative polymerase chain reaction (qPCR) demonstrated the passage-dependent expression of oxidative stress-related genes and sirtuins in response to CoQ10 treatment. (3) Results: CoQ10 enhanced basal respiration and spare respiratory capacity (SRC), particularly in older senescent cells. CoQ10 improved basal respiration and ATP-linked oxygen consumption in young MSCs and partially restored these functions in aged MSCs. Moreover, CoQ10 increased saturated fatty acids, particularly in young cells, and decreased monounsaturated fatty acids in aged cells. qPCR analysis revealed passage-dependent modifications in oxidative stress-related genes and sirtuin expression; CoQ10 exposure significantly influenced SIRT1 and SIRT3 activity, leading to an increase in PPARγ and CAT expression. (4) Conclusions: these results highlight CoQ10’s potential to alleviate mitochondrial dysfunction and metabolic shifts associated with cellular aging, underscoring its therapeutic value for age-related mitochondrial and metabolic disorders. Full article

Physical exercise is an essential component of human health. In recent years, scientific research has focused on identifying natural compounds and formulating new supplements aimed at enhancing athletic performance, accelerating muscle recovery, and minimizing the damage caused by physical exertion. The use of antioxidants to counteract the formation of reactive oxygen species (ROS) following physical activity (PA) is already a widely adopted practice. Resveratrol (RES), a polyphenol belonging to the stilbene class, is well known for its potent antioxidant activity and anti-inflammatory effects primarily attributed to the activation of sirtuins. RES possesses multiple nutraceutical properties used for the prevention and treatment of inflammatory, cardiovascular, neoplastic, and infectious diseases, thus attracting attention to study its use in combination with physical exercise to promote well-being. Animal trials combining RES and PA have mainly reported improvements in muscle, energy, and cardiovascular functions. The data presented and discussed in this narrative review are from Pubmed, Scopus, and the Human Gene Database (search limited to 2011 to 2025 with the keywords RES, sirtuins, and physical activity altogether or in combination with each other). This review gathers several studies on RES focusing on its nutraceutical properties, epigenetic activities via sirtuins, and the potential benefits of combining RES with PA in maintaining health and well-being based on trials performed first in animals and later in humans. Human studies have been conducted on various populations, including active adults, sedentary individuals, patients with diseases, and elderly individuals. Some studies have confirmed the benefits of RES observed in animal experiments. However, in some cases, no substantial differences were found between RES supplementation and the control group. In conclusion, the benefits of RES on PA reported in the literature are still not fully evident, given the contrasting studies and the still limited number of trials, but both RES and PA are successful tools for the maintenance of health and wellbeing. Full article

Background/Objectives: The consumption of food rich in anthocyanins, a natural pigment found in plants, has been associated with improved joint health. However, systematic efforts to summarise the effects of anthocyanins and their deglycosylated forms, anthocyanidins, in managing osteoarthritis (OA) are lacking. This scoping review aims to comprehensively summarise the current evidence regarding the role of anthocyanins and anthocyanidins in OA management and highlights potential research areas. Methods: A comprehensive literature search was performed using PubMed, Scopus, and Web of Science in January 2025 to look for primary studies published in English, with the main objective of investigating the chondroprotective effects of anthocyanins and anthocyanidins, regardless of their study designs. Results: The seven included studies showed that anthocyanins and anthocyanidins suppressed the activation of inflammatory signalling, upregulated sirtuin-6 (cyanidin only), and autophagy (delphinidin only) in chondrocytes challenged with various stimuli (interleukin-1β, oxidative stress, or advanced glycation products). Anthocyanins also preserved cartilage integrity and increased the pain threshold in animal models of OA. No clinical trial was found in this field, suggesting a translation gap. Conclusions: In conclusion, anthocyanins and anthocyanidins are potential chondroprotective agents, but more investigations are required to overcome the gap in clinical translation. Full article

Background/Objectives: Addressing the risk of malnutrition at an early stage is crucial to preventing its development, which can have a detrimental impact on physical and mental health status. This study investigates the potential role of biochemical biomarkers such as sirtuin 1 (SIRT-1), melatonin, cholecystokinin-8 (CCK-8), and total antioxidant capacity (TAC) in identifying the risk of malnutrition. Methods: This cross-sectional study assessed malnutrition risk in 153 community-dwelling older adults using the Mini Nutritional Assessment (MNA). Serum levels of SIRT-1, melatonin, and CCK-8 were analyzed with enzyme-linked immunosorbent assay (ELISA), and total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) method. Results: Serum levels of TAC and CCK-8 were significantly positively correlated with grip strength and visceral adipose tissue, with TAC levels also showing associations with appendicular skeletal muscle mass index (ASMI), total body water, total energy expenditure, fat-free mass index, and fat mass index (p < 0.001). CCK-8 emerged as a strong predictor of malnutrition risk (AUC = 0.58 in females, AUC = 0.64 in males), whereas SIRT-1 (AUC = 0.57 for both sexes), melatonin (AUC = 0.46 for females, AUC = 0.51 for males), and TAC (AUC = 0.42 for females, AUC = 0.54 for males) exhibited weaker predictive abilities. A multivariate model incorporating CCK-8 demonstrated excellent predictive accuracy (AUC = 0.84, 95% CI: 0.77–0.90) and indicated a potential association between elevated CCK-8 levels and a higher risk of malnutrition. Conclusions: In conclusion, this study highlights the effectiveness of a multi-parameter model incorporating CCK-8 as a reliable approach for assessing malnutrition risk in older adults, offering a comprehensive evaluation of the condition. However, further research is needed to confirm its applicability and accuracy in diverse elderly populations and clinical settings. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

It is well established that phenolic compounds from plant sources impact readouts of cell health such as reduced radical and reactive oxygen species. However, it is unclear if specific phenolic structures impact other cellular processes or proteins, such as the evolutionary conserved deacetylase Sirtuin 1 (SIRT1), and if phenolic combinations interact synergistically to do so. We observed that structurally diverse haskap berry phenolics (caffeic acid, cyanidin, kaempferol-3-O-glucoside, and gentisic acid) differentially impacted normal primary human fibroblast growth, which has been linked to SIRT1. These results were consistent with previous work from our lab indicating that haskap phenolic extracts/fractions impact human cell growth via SIRT1-dependent mechanisms. Therefore, we furthered the investigation into SIRT1 and phenolic structure and observed that the individual phenolics or their combinations had no observable impact on SIRT1 transcript abundance or cellular localization. We also observed that select phenolics decreased SIRT1 protein abundance and increased SIRT1 activity. The catechol-containing phenolics outperformed those that lack a catechol group, indicating potential structure-dependent impact(s). Potential synergy between the specific phenolics analyzed was observed in Western blot, and potential antagonism was identified in the SIRT1 activity assay. Results were concomitant with the presence of different phenolic structures, phenolic combinations, and cell type (sex and/or individual differences). These results highlight the possible significance of the catechol structure and indicate that phenolics have the potential to impact cell processes, which the authors hypothesize to be due to mechanisms that are independent of antioxidant activity. Full article

Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as a novel food for human consumption in 2014, and as a food supplement in 2017. This narrative review will provide an overview of preclinical and clinical trials assessing the efficacy of a T. chuii-derived ingredient, characterized by a high superoxide dismutase (SOD) activity (SOD-rich T. chuii), to improve various aspects of cellular health. Collectively, results from in vitro, and more importantly in vivo research, support SOD-rich T. chuii as a potential promoter of cellular health. Principally, the ingredient appears to function as an indirect antioxidant by boosting intracellular antioxidant systems. Moreover, it can positively modulate inflammatory status by up-regulating anti-inflammatory and down-regulating pro-inflammatory cytokines and factors. In addition, SOD-rich T. chuii appears to promote cellular health though protecting from DNA damage, boosting immune function, strengthening cell structure and integrity, and positively modulating cell signaling pathways. There is also some evidence to suggest that SOD-rich T. chuii may improve aspects of mitochondrial function through the up-regulation of genes linked to mitochondrial biogenesis and ATP synthesis. From the trials conducted to date, transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) appear to be important in mediating the effects of SOD-rich T. chuii on cellular health. These exciting preliminary observations suggest that SOD-rich T. chuii may represent a natural blue food supplement with the potential to enhance various aspects of cellular health. Full article

The metabolic poise, or balance, between glycolysis and fatty acid oxidation (FAO) has recently been found to play a critical role in osteogenic differentiation and homeostasis. While simulated microgravity (SMG) is known to impede osteoblast differentiation (OBD) by inhibiting the Wnt/β-catenin pathway, how it affects osteoblast metabolism in this context remains unclear. We previously analyzed the effect of SMG on the differentiation of pre-osteoblast MC3T3-E1 cells and found that it reduced focal adhesion kinase (FAK) activity. This, in turn, downregulated Wnt/β-catenin and two of its downstream targets critical for OBD bone morphogenic protein-2 (BMP2) and type-1 collagen (COL1) formation, leading to a reduction in alkaline phosphatase (ALP) activity and cell matrix mineralization. In this study, we further analyzed how SMG-induced alterations in energy metabolism contribute to the inhibition of OBD in MC3T3-E1 cells. Consistent with our earlier findings, we demonstrated that SMG inhibits OBD by downregulating the collective activity of FAK and the Wnt/β-catenin-BMP2-COL1 transcriptional pathway. Interestingly, we observed that SMG also reduces the abundance of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and carnitine palmitoyl transferase-1α (CPT1A), which are all key metabolic factors regulating mitochondrial number and FAO capacity. Accordingly, we found that the mitochondrial content and FAO potential of MC3T3-E1 cells were lower upon exposure to SMG but were both rescued upon administration of the FAK activator cytotoxic necrotizing factor-1 (CNF1), thereby allowing cells to overcome SMG-induced inhibition of OBD. Taken together, our study indicates that the metabolic regulator SIRT1 may be a new target for reversing SMG-induced bone loss. Full article

Metabolic cardiomyopathy, encompassing diabetic and obese cardiomyopathy, is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 and type 2 diabetes, and obesity. These conditions induce structural and functional alterations in the heart, including left ventricular dysfunction, fibrosis, and ultimately heart failure, particularly in the presence of coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, is frequently disrupted in metabolic cardiomyopathy. This review explores the role of autophagy in the pathogenesis of high-fat diet (HFD) and streptozotocin (STZ)-induced metabolic cardiomyopathy, focusing on non-selective and selective autophagy pathways, including mitophagy, ER-phagy, and ferritinophagy. Key proteins and genes such as PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, and miR-34a are central to the regulation of autophagy in metabolic cardiomyopathy. Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, and drives fibrosis in the heart. Additionally, selective autophagy processes such as lipophagy, regulated by PNPLA8, and ferritinophagy, modulated by NCOA4, play pivotal roles in lipid metabolism and iron homeostasis. Emerging therapeutic strategies targeting autophagy, including plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds (e.g., sirtuin 3, LC3), and lipid/glucose-lowering drugs, offer promising avenues for mitigating the effects of metabolic cardiomyopathy. Despite recent advances, the precise mechanisms underlying autophagy in this context remain poorly understood. A deeper understanding of autophagy’s regulatory networks, particularly involving these critical genes and proteins, may lead to novel therapeutic approaches for treating metabolic cardiomyopathy. Full article

Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy. Full article

Acetic acid bacteria are single-celled organisms well-known for their ability to convert ethanol into acetic acid. Still, recent research suggests they may harbor another attractive characteristic—the production of proteins with remarkable similarities to sirtuins. Sirtuins have been linked to lifespan extension in various organisms, raising intriguing questions about the potential connection between acetic acid bacteria and the biology of aging. This article delves into the characterization of sirtuin homologs in acetic acid bacteria. Up to three types of sirtuin homologs have been identified in 21% of acetic acid bacteria genomes deposited in NCBI. All three types were present only in the genera Acetobacter and Novacetimonas, which are known to survive in the harshest environmental conditions (high concentrations of acetic acid and ethanol). Interestingly, two types of these sirtuin homologs (SirAAB-L and SirAAB-S) constitute a separate group (SirAAB), distinctive from all other presently known sirtuins. The results obtained in silico thus encourage further studies into the function of these types of sirtuins and their interplay with metabolic pathways in these industrially important bacteria. Full article

Enterovirus 68 (EV-D68) is a non-enveloped virus with a positive-sense single-stranded RNA genome that causes respiratory diseases and acute flaccid myelitis, posing significant threats to human health. However, an effective vaccine remains undeveloped. SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme, plays a key role in cellular metabolism, but its interaction with NAD+ during viral infections is not well understood. In this study, through a metabolomics analysis, we demonstrate that EV-D68 infection influences cellular metabolism. Additionally, we show that NAD+ inhibits EV-D68 infection both in vivo and in vitro. EV-D68 reduces cellular NAD+ levels by regulating the expression of enzymes involved in NAD+ consumption and synthesis. Moreover, the infection increases the expression of sirtuin 1 (SIRT1), which inhibits EV-D68 replication in turn. Mechanistically, SIRT1 suppresses EV-D68 5′UTR-mediated translation, and the antiviral effect of SIRT1 on EV-D68 replication is enhanced by NAD+. Collectively, our findings highlight the critical role of NAD+ metabolism in EV-D68 infection and reveal the antiviral potential of SIRT1, providing valuable insights for the development of antiviral strategies. Full article

Mitochondria play a central role in cell biological processes, functioning not only as producers of ATP but also as regulators of Ca²⁺ signaling. Mitochondrial calcium uptake occurs primarily through the mitochondrial calcium uniporter channel (mtCU), with the mitochondrial calcium uptake subunits 1, 2, and 3 (MICU1, MICU2, and MICU3) serving as the main regulatory components. Dysregulated mitochondrial calcium uptake is a hallmark of cellular degeneration. Sirtuin 1 (SIRT1), a key regulator of cellular metabolism, plays a critical role in aging and various neurodegenerative conditions. By blocking SIRT1 using EX527 or shSIRT1, we observed mitochondrial structural fragmentation as well as intensified and prolonged mitochondrial calcium overload. Our study revealed a direct interaction between SIRT1 and MICU1. Notably, SIRT1 inhibition resulted in reduced MICU1 expression, hence led to mitochondrial calcium overload, illustrating the unconventional role of SIRT1 in governing mitochondrial function. Full article