Long-term adherence to dietary interventions remains a major challenge in the management of overweight and obesity. Feeding behavior is regulated by homeostatic mechanisms within hypothalamic circuits and hedonic-motivational processes mediated by mesocorticolimbic pathways. These systems are influenced by neuroendocrine signals, inflammatory status, and metabolic cues that shape appetite and reward-driven eating. Among nutritional factors, the balance between omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) has emerged as a key modulator of these processes. This mini-review examines how PUFA balance influences hypothalamic energy homeostasis regulation, enteroendocrine signaling, reward circuits, and gut microbiota. A high omega-6/omega-3 ratio promotes inflammation, enhances endocannabinoid signaling, impairs insulin sensitivity, and increases reward-driven feeding. Conversely, increasing omega-3 availability shifts PUFA balance toward anti-inflammatory states, improves metabolic and satiety signaling, and reduces the drive to eat. Circulating fatty acid profiles provide objective indicators of dietary intake and may help assess adherence to dietary patterns. The evidence reviewed here provides a biological framework supporting a potential link between dietary fatty acid composition and long-term adherence, warranting further investigation.

Palmitic acid (PA), the most abundant saturated fatty acid (SFA) in humans, plays a key role in energy metabolism, membrane synthesis, and signaling. Oligodendrocyte precursor cells (OPCs), which generate mature oligodendrocytes (OLs) forming the myelin sheath, are responsive to metabolic and redox signals. Despite increasing interest in lipid metabolism and mitochondrial dynamics as regulators of OPC fate, the effects of PA remain unclear. This study investigates the biphasic, dose-dependent effects of PA on OPCs using the oligodendrocyte precursor MO3.13 cell line and employs rat organotypic slice cultures to evaluate the effects of non-toxic PA doses under pathological conditions and on axonal (re)-myelination. In MO3.13 cells, high-dose PA (100 µM) induces mitochondrial fragmentation and caspase-7 activation, accompanied by reduced mitofusin-2 (MFN2) and phosphorylated dynamin-related protein 1 at Ser616 (p-DRP1), indicating altered fusion-fission balance and impaired reactive oxygen species (ROS) generation. In contrast, low-dose PA (25 µM) triggers a protective response involving nuclear factor erythroid 2-related factor 2 (Nrf2) activation and upregulation of antioxidant and lipid-regulatory genes (glutamate-cysteine ligase modifier subunit [GCLM], NAD(P)H dehydrogenase [quinone] 1 [NQO1], peroxisome proliferator-activated receptor gamma [PPARγ], and cluster of differentiation 36 [CD36]) resulting in reduced intracellular ROS and enhanced lipid mobilization. PA 25 µM promotes OPC differentiation by inhibiting migration and cell cycle progression and increasing myelin basic protein (MBP) and proteolipid protein (PLP) expression. Notably, early exposure (1 day) favors mitochondrial fusion, whereas prolonged exposure (4 days) shows a physiological shift to fission. PA 25 µM prevents neurodegeneration in hippocampal organotypic slice cultures exposed to a neuroinflammatory insult. In cerebellar organotypic slice cultures, PA 25 µM enhances axonal myelination and accelerates remyelination following lysolecithin-induced demyelination. These findings highlight the physiological relevance of low-dose PA in modulating OLs.

The pivotal role of reactive oxygen species (ROS), especially peroxides, in multiple cell signalling pathways has been well-established. Superoxide dismutase 1 (SOD-1) represents a major intracellular source of hydrogen peroxide. Antigen-dependent activation of human T lymphocytes has been previously described by us to induce both SOD-1 production and secretion by T cells. SOD-1 mediated pathways have also been described to deliver proinflammatory signals and to affect the differentiation of immune-suppressor subsets (Treg). The mechanisms underlying extracellular SOD-1 export by activated T cells remain largely undefined. Indeed, SOD-1, like the leaderless proteins, is unable to exploit the conventional trans-Golgi vesicular secretion pathway. Here, we propose that ABCA1 transporters play a role in the mechanisms underlying SOD-1 secretion by activated T cells. Indeed, ABC transporter inhibition by using glyburide significantly decreases SOD-1 secretion by antigen-triggered human T cells in vitro. The effect has been confirmed by using four different detection techniques, as represented by Western blotting, ELISA, flow cytometry and confocal microscopy. Collectively, our findings indicate that ABCA1 transporter-dependent secretion supports the vesicular secretory machinery and might contribute to the extracellular release of SOD-1 by activated T cells. This mechanism highlights ABCA1 as a promising molecular target for therapeutic modulation of deranged immune activation.

This study evaluated the effect of a nutraceutical supplementation (NS) and Mediterranean hypocaloric diet (MHD) on hepatic steatosis indices (HSIs), γ-glutamyl transferase (γGT), and lipid profile in adults with hyperlipidemia and nonalcoholic fatty liver disease (NAFLD). In vitro study on HepG2 cells explored potential molecular mechanisms. A retrospective study was conducted on 45 overweight/obese subjects (19 M) prescribed MHD with/without NS. Anthropometric data, biochemical parameters, HSIs, and γGT were collected at baseline and after 3 months. In vitro, cells were pretreated with single and mixed NS components and then with tumor necrosis factor α (TNFα) or fatty acids (FAs). Antioxidant and antiinflammatory activities were evaluated by fluorescence assays and quantitative polymerase chain reaction or enzyme-linked immunosorbent assay; antiapoptotic effects by Western blot. After 3 months, all subjects improved anthropometric and biochemical parameters but only the combined MHD and NS treatment significantly reduced insulin resistance, HSIs, low-density lipoprotein cholesterol, and γGT. In vitro, treatment with mixed NS components decreased TNFα-/FAs-induced reactive oxygen species. Combined treatment also modulated the inflammatory response by lowering interleukin-6 and interleukin-1β, increasing interleukin-10 and pro-caspase 8 expression. These findings suggest that NS, due to its antiinflammatory properties, represents a promising strategy for NAFLD management.

Multiple sclerosis (MS) is an autoimmune chronic disease characterized by inflammation and demyelination of the central nervous system (CNS). Despite numerous studies conducted, valid biomarkers enabling a definitive diagnosis of MS are not yet available. The aim of our study was to identify a marker from a blood sample to ease the diagnosis of MS. In this study, since there is evidence connecting the serotonin pathway to MS, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to detect serum MS-specific auto-antibodies (auto-Ab) against the extracellular loop 1 (ECL-1) of the 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A). We utilized an ELISA format employing poly-D-lysine as a pre-coating agent. The binding of 208 serum samples from controls, both healthy and pathological, and of 104 serum samples from relapsing–remitting MS (RRMS) patients was tested. We observed that the serum-binding activity in control cohort sera, including those with autoimmune and neurological diseases, was ten times lower compared to the RRMS patient cohort (p = 1.2 × 10−47), with a sensitivity and a specificity of 98% and 100%, respectively. These results show that in the serum of patients with MS there are auto-Ab against the serotonin receptor type 2A which can be successfully used in the diagnosis of MS due to their high sensitivity and specificity.

Chlorogenic acid (CGA), a polyphenol found mainly in coffee and tea, exerts antioxidant, anti-inflammatory and anti-apoptotic effects at the gastrointestinal level. However, although CGA is known to cross the blood–brain barrier (BBB), its effects on the CNS are still unknown. Oligodendrocytes (OLs), the myelin-forming cells in the CNS, are the main target in demyelinating neuroinflammatory diseases such as multiple sclerosis (MS). We evaluated the antioxidant, anti-inflammatory and anti-apoptotic roles of CGA in M03-13, an immortalized human OL cell line. We found that CGA reduces intracellular superoxide ions, mitochondrial reactive oxygen species (ROS) and NADPH oxidases (NOXs) /dual oxidase 2 (DUOX2) protein levels. The stimulation of M03-13 cells with TNFα activates the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway, leading to an increase in superoxide ion, NOXs/DUOX2 and phosphorylated extracellular regulated protein kinase (pERK) levels. In addition, tumor necrosis factor alpha (TNF-α) stimulation induces caspase 8 activation and the cleavage of poly-ADP-ribose polymerase (PARP). All these TNFα-induced effects are reversed by CGA. Furthermore, CGA induces a blockade of proliferation, driving cells to differentiation, resulting in increased mRNA levels of myelin basic protein (MBP) and proteolipid protein (PLP), which are major markers of mature OLs. Overall, these data suggest that dietary supplementation with this polyphenol could play an important beneficial role in autoimmune neuroinflammatory diseases such as MS.

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Astrocytes and microglial cells play a critical role also for their ability to enhance a deranged inflammatory response. Excitotoxicity, due to excessive glutamate levels and increased intracellular Ca2+ concentration, has also been proposed to play a key role in ALS pathogenesis/progression. Reactive Oxygen Species (ROS) behave as key second messengers for multiple receptor/ligand interactions. ROS-dependent regulatory networks are usually mediated by peroxides. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. Both, neuron depolarization and antigen-dependent T-cell activation mediate SOD1 exocytosis, inducing increased interaction of the enzyme with a complex molecular network involved in the regulation of neuron functional activity and immune response. Here, alteration of SOD1-dependent pathways mediating increased intracellular Ca2+ levels, altered mitochondria functions and defective inflammatory process regulation have been proposed to be relevant for ALS pathogenesis/progression.

Multiple sclerosis (MS) is a multifactorial, immune-mediated disease caused by complex gene-environment interactions. Dietary factors modulating the inflammatory status through the control of the metabolic and inflammatory pathways and the composition of commensal gut microbiota, are among the main environmental factors involved in the pathogenesis of MS. There is no etiological therapy for MS and the drugs currently used, often accompanied by major side effects, are represented by immunomodulatory substances capable of modifying the course of the disease. For this reason, nowadays, more attention is paid to alternative therapies with natural substances with anti-inflammatory and antioxidant effects, as adjuvants of classical therapies. Among natural substances with beneficial effects on human health, polyphenols are assuming an increasing interest due to their powerful antioxidant, anti-inflammatory, and neuroprotective effects. Beneficial properties of polyphenols on the CNS are achieved through direct effects depending on their ability to cross the blood-brain barrier and indirect effects exerted in part via interaction with the microbiota. The aim of this review is to examine the literature about the molecular mechanism underlying the protective effects of polyphenols in MS achieved by experiments conducted in vitro and in animal models of the disease. Significant data have been accumulated for resveratrol, curcumin, luteolin, quercetin, and hydroxytyrosol, and therefore we will focus on the results obtained with these polyphenols. Clinical evidence for the use of polyphenols as adjuvant therapy in MS is restricted to a smaller number of substances, mainly curcumin and epigallocatechin gallate. In the last part of the review, a clinical trial studying the effects of these polyphenols in MS patients will also be revised.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Inside the adult CNS, oligodendrocyte progenitor cells (OPCS) are able to proliferate, migrate and differentiate into mature oligodendrocytes (OLs) which are responsible for the production of myelin sheet and energy supply for neurons. Moreover, in demyelinating diseases, OPCs are recruited to the lesion areas where they undergo differentiation and myelin synthesis. Serotonin (5-hydroxytryptamine, 5-HT) is involved in OLs’ development and myelination, but so far the molecular mechanisms involved or the effects of 5-HT on mitochondria function have not yet been well documented. Our data show that 5-HT inhibits migration and proliferation committing cells toward differentiation in an immortalized human oligodendrocyte precursor cell line, M03-13. Migration blockage is mediated by reactive oxygen species (ROS) generation since antioxidants, such as Vit C and Cu-Zn superoxide dismutase, prevent the inhibitory effects of 5-HT on cell migration. 5-HT inhibits OPC migration and proliferation and increases OL phenotypic markers myelin basic protein (MBP) and Olig-2 via protein kinase C (PKC) activation since the inhibitor of PKC, bis-indolyl-maleimide (BIM), counteracts 5-HT effects. NOX inhibitors as well, reverse the effects of 5-HT, indicating that 5-HT influences the maturation process of OPCs by NOX-dependent ROS production. Finally, 5-HT increases mitochondria function and antioxidant activity. The identification of the molecular mechanisms underlying the effects of 5-HT on maturation and energy metabolism of OPCs could pave the way for the development of new treatments for autoimmune demyelinating diseases such as Multiple Sclerosis where oligodendrocytes are the primary target of immune attack.

Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation.

Renin–angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion–reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood–brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion–reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion–reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

The renin angiotensin system and the cholinergic anti-inflammatory pathway have been recently shown to modulate lung inflammation in patients with COVID-19. We will show how studies performed on this disease are starting to provide evidence that these two anti-inflammatory systems may functionally interact with each other, a mechanism that could have a more general physiological relevance than only COVID-19 infection.

Energy metabolism and redox state are strictly linked; energy metabolism is a source of reactive oxygen species (ROS) that, in turn, regulate the flux of metabolic pathways. Moreover, to assure redox homeostasis, metabolic pathways and antioxidant systems are often coordinately regulated. Several findings show that superoxide dismutase 1 (SOD1) enzyme has effects that go beyond its superoxide dismutase activity and that its functions are not limited to the intracellular compartment. Indeed, SOD1 is secreted through unconventional secretory pathways, carries out paracrine functions and circulates in the blood bound to lipoproteins. Striking experimental evidence links SOD1 to the redox regulation of metabolism. Important clues are provided by the systemic effects on energy metabolism observed in mutant SOD1-mediated amyotrophic lateral sclerosis (ALS). The purpose of this review is to analyze in detail the involvement of SOD1 in redox regulation of metabolism, nutrient sensing, cholesterol metabolism and regulation of mitochondrial respiration. The scientific literature on the relationship between ALS, mutated SOD1 and metabolism will also be explored, in order to highlight the metabolic functions of SOD1 whose biological role still presents numerous unexplored aspects that deserve further investigation.

A common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles. Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress. Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle. The nuclear factor erythroid 2-related factor 2 (Nrf2) controls adaptive responses and remains the major regulator of quenching mechanisms underlying different types of stress. Here, we demonstrate a positive role of fasting as a protective mechanism against oxidative stress in skeletal muscle. In particular, by using in vivo and in vitro models of fasting, we found that typical Nrf2-dependent genes, including those controlling iron (e.g., Ho-1) and glutathione (GSH) metabolism (e.g., Gcl, Gsr) are induced along with increased levels of the glutathione peroxidase 4 (Gpx4), a GSH-dependent antioxidant enzyme. These events are associated with a significant reduction in malondialdehyde, a well-known by-product of lipid peroxidation. Our results suggest that fasting could be a valuable approach to boost the adaptive anti-oxidant responses in skeletal muscle.

OBJECTIVES:Using the new European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, we identified sarcopenic and dynapenic patients in a cohort of predialysis patients with chronic kidney disease (CKD), and evaluated their clinical and laboratory characteristics. METHODS:The study population consisted of 85 (55 men) clinically stable predialysis CKD patients (92.9% in stages 3-5), with a median age of 65.0 (52.5-72.0) y. We classified as sarcopenic the patients with handgrip strength (HGS) and muscle mass both lower than the respective EWGSOP2 cutoff values and as dynapenic those in whom only HGS was less than these reference values. HGS was measured with a hand dynamometer, whereas muscle mass was measured by bioimpedance analysis. Renal function was evaluated as Modification of Diet in Renal Disease estimated glomerular filtration rate. RESULTS:The prevalence of sarcopenia and dynapenia was, respectively, 7.1% and 17.6%. As reported in previous studies, serum albumin and hemoglobin were lower in sarcopenic patients than in patients with preserved muscle mass and strength. However, unlike in these studies, sarcopenia prevalence did not increase with CKD stage, and estimated glomerular filtration rate was similar between groups. Moreover, no difference was identified in any of the aforementioned parameters between dynapenic patients and patients with preserved muscle mass and strength. CONCLUSIONS:The EWGSOP2 criteria identified sarcopenia in CKD with a prevalence similar to previous diagnostic criteria. In addition, they found that dynapenia was highly prevalent. Nevertheless, the EWGSOP2 criteria could be better adapted to CKD patients to improve their ability to detect high-risk sarcopenic and dynapenic patients.

Objective: Glucans are already known as biological modifiers of the immune system and cytokine modulation (IFN-y; TNF; T-CD4/CD8), but the role of low molecular weight glucans on transcriptome regulation is not well documented. Materials and Methods: In this paper, the mechanism of action of a mix in capsules of 0.6 g of beta-Glucan (Active hexose correlated compound "AHCC" and beta-Glucan 1,3-1,6) on the neoplastic cell line transcriptome has been explored. The cellular models used were Caco2 and LS174T cell lines. Transcriptome analysis was performed by RNA expression analysis of transcripts of both single and multiple samples. The analysis was completed with the aid of information technology. Results: ROS (Reactive Oxygen Species) decrease following glucans treatment (Figure 1) combined with a marked improvement in the Redox control of SOD1 (Superoxide Dismutase 1) (Figure 2), which is pre-sent in the cytosol of all eukaryotic cells with copper and zinc (Cu-Zn-SOD). Following glucan mix treatment, COX-2 (cyclooxygenase-2) expression levels showed a marked reduction (Figure 3A). The combined glucan treatment on the two cell lines showed an over expression of SOD1 with a significant reduction in COX-2 expression (Figure 3A). Pro-inflammatory cytokines such as IL-1, IL-6, TNF-alpha, were consequently down-expressed (Figure 3B, C, D). Conclusions: The glucan mix reduces ROS significantly, decreasing COX-2 expression, reducing the inflammatory state and consequently decreasing TNF-alpha and IL-1.

OPINION article Front. Cell. Infect. Microbiol., 15 December 2020Sec. Virus and Host Volume 10 - 2020 | https://doi.org/10.3389/fcimb.2020.608435

Glucans are complex polysaccharides consisting of repeated units of d-glucose linked by glycosidic bonds. The nutritional contribution in α-glucans is mainly given by starch and glycogen while in β-glucans by mushrooms, yeasts and whole grains, such as barley and spelt well represented in the Mediterranean Diet. Numerous and extensive studies performed on glucans highlighted their marked anti-tumor, antioxidant and immunomodulatory activity. It has recently been shown that rather than merely being a passive barrier, the intestinal epithelium is an essential modulator of immunity. Indeed, epithelial absorptive enterocytes and mucin secreting goblet cells can produce specific immune modulating factors, driving innate immunity to pathogens as well as preventing autoimmunity. Despite the clear evidence of the effects of glucans on immune system cells, there are only limited data about their effects on immune activity of mucosal intestinal cells strictly related to intestinal barrier integrity. The aim of the study was to evaluate the effects of α and β glucans, alone or in combination with other substances with antioxidant properties, on reactive oxygen species (ROS) levels, on the expression of ROS-generating enzyme DUOX-2 and of the immune modulating factors Tumor Necrosis Factor (TNF-α), Interleukin 1 β (IL-1β) and cyclooxygenase-2 (COX-2) in two intestinal epithelial cells, the enterocyte-like Caco-2 cells and goblet cell-like LS174T.In our research, the experiments were carried out incubating the cells with glucans for 18 h in culture medium containing 0.2% FBS and measuring ROS levels fluorimetrically as dihydrodichlorofluoresce diacetate (DCF-DA) fluorescence, protein levels of DUOX-2 by Western blotting and mRNA levels of, TNF-α, IL-1β and COX-2 by qRT-PCR. α and β glucans decreased ROS levels in Caco-2 and LS 174T cells. The expression levels of COX-2, TNF-α, and IL-1β were also reduced by α- and β-glucans. Additive effects on the expression of these immune modulating factors were exerted by vitamin C. In Caco-2 cells, the dual oxidase DUOX-2 expression is positively modulated by ROS. Accordingly, in Caco-2 or LS174T cells treated with α and β-glucans alone or in combination with Vitamin C, the decrease of ROS levels was associated with a reduced expression of DUOX-2. The treatment of cells with the NADPH oxidase (NOX) inhibitor apocynin decrease ROS, DUOX-2, COX-2, TNF-α and IL-1β levels indicating that NOX dependent ROS regulate the expression of immune modulating factors of intestinal cells. However, the combination of vitamin C, α and β-glucans with apocynin did not exert an additive effect on COX-2, TNF-α and IL-1β levels when compared with α-, β-glucans and Vitamin C alone. The present study showing a modulatory effect of α and β-glucans on ROS and on the expression of immune modulating factors in intestinal epithelial cells suggests that the assumption of food containing high levels of these substances or dietary supplementation can contribute to normal immunomodulatory function of intestinal barrier.

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength. In older people, malnutrition and physical inactivity are often associated with sarcopenia, and, therefore, dietary interventions and exercise must be considered to prevent, delay, or treat it. Among the pathophysiological mechanisms leading to sarcopenia, a key role is played by an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and a decrease in enzymatic antioxidant protection leading to oxidative stress. Many studies have evaluated, in addition to the effects of exercise, the effects of antioxidant dietary supplements in limiting age-related muscle mass and performance, but the data which have been reported are conflicting. In skeletal muscle, ROS/RNS have a dual function: at low levels they increase muscle force and adaptation to exercise, while at high levels they lead to a decline of muscle performance. Controversial results obtained with antioxidant supplementation in older persons could in part reflect the lack of univocal effects of ROS on muscle mass and function. The purpose of this review is to examine the molecular mechanisms underlying the dual effects of ROS in skeletal muscle function and the analysis of literature data on dietary antioxidant supplementation associated with exercise in normal and sarcopenic subjects.