Alteration of Immunoregulatory Patterns and Survival Advantage of Key Cell Types in Food Allergic Children.

All allergic responses to food indicate the failure of immunological tolerance, but it is unclear why cow's milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (n = 6) and PN (n = 18) and non-allergic (NA) (n = 8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen-stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children, constitutively high plasma levels IL-1ß, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by the spontaneous secretion of sCD23, IL-1ß, IL-2, IL-4, IL-5, IL-10, IL-12p70, IFN-γ and TNF-α in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69+ subsets. Cells were generally refractory to antigenic stimulation in vitro, but IL-4 neutralization led to CD152 downregulation by CD4+ T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most importantly, higher Bcl-2 content within key effector cells implies survival advantage with the potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions.

Development and validation of derivatization-based LC-MS/MS method for quantification of short-chain fatty acids in human, rat, and mouse plasma.

Short-chain fatty acids (SCFAs), the end products of gut microbial fermentation of dietary fibers and non-digestible polysaccharides, act as a link between the microbiome, immune system, and inflammatory processes. The importance of accurately quantifying SCFAs in plasma has recently emerged to understand their biological role. In this work, a sensitive and reproducible LC-MS/MS method is reported for SCFAs quantification in three different matrices such as human, rat and mouse plasma via derivatization, using as derivatizing agent O-benzylhydroxylamine (O-BHA), coupled with liquid-liquid extraction. First, the instrumental parameters of the mass spectrometer and then the chromatographic conditions were optimized using previously SCFAs derivatives synthetized and used as standards. After that, the best conditions for derivatization and extraction from plasma were studied and a series of determinations were performed on human, rat, and mouse plasma aliquots to validate the overall method (derivatization, extraction, and LC-MS/MS determination). The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%) and sensitivity (LOQ of 0.01 µM for acetic, butyric, propionic and isobutyric acid) in all plasma samples. The method thus developed and validated was applied to the quantification of major SCFAs in adult and aged mice, germ-free mice and in germ-free recipient mice subjected to fecal transplant from adult and aged donors. Results highlighted how plasma concentrations of SCFAs are correlated with age further highlighting the importance of developing a method that is reliable for the quantification of SCFAs to study their biological role.

Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes.

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs' extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial-mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therapy.

Morphological and Functional Effects of Ultrasound on Blood-Brain Barrier Transitory Opening: An In Vitro Study on Rat Brain Endothelial Cells.

With the recent advances in medicine, human life expectancy is increasing; however, the extra years of life are not necessarily spent in good health or free from disability, resulting in a significantly higher incidence of age-associated pathologies. Among these disorders, neurodegenerative diseases have a significant impact. To this end, the presence of the protective blood-brain barrier (BBB) represents a formidable obstacle to the delivery of therapeutics. Thus, this makes it imperative to define strategies to bypass the BBB in order to successfully target the brain with the appropriate drugs. It has been demonstrated that targeting the BBB by ultrasound (US) can transiently make this anatomical barrier permeable and in so doing, allow the delivery of therapeutics. Thus, our aim was to carry out an in depth in vitro molecular and morphological study on the effects of US treatment on the BBB. The rat brain endothelial (RBE4) cell line was challenged with exposure to 12 MHz diagnostic US treatment for 10, 20, and 30 min. Cell viability assays, Western blotting analysis on the endoplasmic reticulum (ER), and oxidative stress marker evaluation were then performed, along with cytological and immunofluorescence staining, in order to evaluate the effects of US on the intercellular spaces and tight junction distribution of the brain endothelial cells. We observed that the US treatment exerted no toxic effects on either RBE4 cell viability or the upregulation/dislocation of the ER and oxidative stress marker (GRP78 and cytochrome C, respectively). Further, we observed that the application of US induced an increase in the intercellular spaces, as shown by Papanicolaou staining, mainly due to the altered distribution of the tight junction protein zonula occludens-1 (ZO-1). This latter US-dependent effect was transient and disappeared 20 min after the removal of the stimulus. In conclusion, our results show that US induces a transient alteration of the BBB, without altering the intracellular signaling pathways such as the ER and oxidative stress that could potentially be toxic for endothelial cells. These results suggested that US treatment could represent a potential strategy for improving drug delivery to the brain.

Case report: A multiple sclerosis patient with imaging features of glymphatic failure benefitted from CSF flow shunting.

The derangement of CSF circulation impacts the functions of the glymphatic-lymphatic system (G-Ls), which regulates solute trafficking and immune surveillance in the CNS. The G-Ls failure leads to the dysregulation of clearance of waste molecules in the brain and to an altered CNS immune response. The imaging features of dilated perivascular spaces imply the impairment of the G-Ls. We report on the case of a patient with primary progressive multiple sclerosis and dilatation of perivascular spaces, who transiently improved after CSF shunt diversions. The underlying mechanisms remain to be determined and at this stage, it is not possible to link CSF diversion to an effect on MS pathology. However, this observation provides the rationale to incentivize research in the largely unknown area of CSF dynamic disturbances on G-Ls failure and ultimately in neurodegeneration.

The Protection of Zinc against Acute Cadmium Exposure: A Morphological and Molecular Study on a BBB In Vitro Model.

Cadmium (Cd) is a well-known occupational and environmental pollutant worldwide, and its toxicity is widely recognised. Cd is reported to increase the permeability of the blood-brain barrier (BBB) and to penetrate and accumulate in the brain. Although many lines of evidence show that Cd toxicity is induced by different mechanisms, one of the best known is the Cd-dependent production of reactive oxygen species (ROS). Zinc is a trace element known as coenzyme and cofactor for many antioxidant proteins, such as metallothioneins and superoxide dismutase enzymes. To date, very little is known about the role of Zn in preventing Cd-induced blood-brain barrier (BBB) alterations. The goal of this study was to test the Zn antioxidant capacity against Cd-dependent alterations in a rat brain endothelial cell line (RBE4), as an in vitro model for BBB. In order to mimic acute Cd poisoning, RBE4 cells were treated with CdCl2 30 µM for 24 h. The protective role of ZnCl2 (50 µM) was revealed by evaluating the cell viability, reactive oxygen species (ROS) quantification, cytochrome C distribution, and the superoxide dismutase (SOD) protein activity. Additionally, the effectiveness of Zn in counteracting the Cd-induced damage was investigated by evaluating the expression levels of proteins already known to be involved in the Cd signalling pathway, such as GRP78 (an endoplasmic reticulum (ER) stress protein), caspase3 pro- and cleaved forms, and BAX. Finally, we evaluated if Zn was able to attenuate the alterations of zonula occludens-1 (ZO-1), one of the tight-junction (TJ) proteins involved in the formation of the BBB. Our data clearly demonstrate that Zn, by protecting from the SOD activity impairment induced by Cd, is able to prevent the triggering of the Cd-dependent signalling pathway that leads to ZO-1 dislocation and downregulation, and BBB damage.

Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence.

ABSTRACT: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.

Light-Induced Smooth Endoplasmic Reticulum Rearrangement in a Unique Interlaced Compartmental Pattern in Macaca mulatta RPE.

Purpose: To investigate light-induced modifications of the smooth endoplasmic reticulum of the RPE in primates. Methods: Eyes of three terminally anesthetized Rhesus monkeys were exposed to 5000 lux for 10 minutes or kept in the dark. Transmission electron microscopy and electron tomography were conducted on small fragments of retina sampled from different regions of the retina. Results: RPE cells smooth endoplasmic reticulum shows a previously unknown arrangement characterized by an interlaced compartmental pattern (ICP). Electron tomograms and 3D-modelling demonstrated that the smooth endoplasmic reticulum with an ICP (ICPSER) consisted of four parallel, independent and interwoven networks of tubules arranged as interconnected coiled coils. Its architecture realized a compact labyrinthine structure of tightly packed tubules stabilized by intertubular filamentous tethers. On average, the ICPSER is present in about 14.6% of RPE cells. Although ICPSER was preferentially found in cells located in the peripheral and in the para/perifoveal retina, ICPSER cells significantly increased in number upon light exposure in the para/perifovea and in the fovea. Conclusions: An ICPSER is apparently a unique feature to primate RPE. Its rapid appearance in the area centralis of the retina upon light exposure suggests a function related to the foveate structure of primate retina or to the diurnal habits of animals that may require additional protection from photo-oxidation or enhanced requests of visual pigments regeneration.

Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly.

Aging is accompanied by physiological changes affecting body composition and functionality, including accumulation of fat mass at the expense of muscle mass, with effects upon morbidity and quality of life. The gut microbiome has recently emerged as a key environmental modifier of human health that can modulate healthy aging and possibly longevity. However, its associations with adiposity in old age are still poorly understood. Here we profiled the gut microbiota in a well-characterized cohort of 201 Italian elderly subjects from the NU-AGE study, by 16S rRNA amplicon sequencing. We then tested for association with body composition from dual-energy X-ray absorptiometry (DXA), with a focus on visceral and subcutaneous adipose tissue. Dietary patterns, serum metabolome and other health-related parameters were also assessed. This study identified distinct compositional structures of the elderly gut microbiota associated with DXA parameters, diet, metabolic profiles and cardio-metabolic risk factors.

Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients.

BACKGROUND: The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions. RESULTS: Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected. CONCLUSION: These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly. Video Abstract.

Dietary Fibre May Mitigate Sarcopenia Risk: Findings from the NU-AGE Cohort of Older European Adults.

Sarcopenia is characterised by a progressive loss of skeletal muscle mass and physical function as well as related metabolic disturbances. While fibre-rich diets can influence metabolic health outcomes, the impact on skeletal muscle mass and function is yet to be determined, and the moderating effects by physical activity (PA) need to be considered. The aim of the present study was to examine links between fibre intake, skeletal muscle mass and physical function in a cohort of older adults from the NU-AGE study. In 981 older adults (71 ± 4 years, 58% female), physical function was assessed using the short-physical performance battery test and handgrip strength. Skeletal muscle mass index (SMI) was derived using dual-energy X-ray absorptiometry (DXA). Dietary fibre intake (FI) was assessed by 7-day food record and PA was objectively determined by accelerometery. General linear models accounting for covariates including PA level, protein intake and metabolic syndrome (MetS) were used. Women above the median FI had significantly higher SMI compared to those below, which remained in fully adjusted models (24.7 ± 0.2% vs. 24.2 ± 0.1%, p = 0.011, η2p = 0.012). In men, the same association was only evident in those without MetS (above median FI: 32.4 ± 0.3% vs. below median FI: 31.3 ± 0.3%, p = 0.005, η2p = 0.035). There was no significant impact of FI on physical function outcomes. The findings from this study suggest a beneficial impact of FI on skeletal muscle mass in older adults. Importantly, this impact is independent of adherence to guidelines for protein intake and PA, which further strengthens the potential role of dietary fibre in preventing sarcopenia. Further experimental work is warranted in order to elucidate the mechanisms underpinning the action of dietary fibre on the regulation of muscle mass.

Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries.

OBJECTIVE: Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. DESIGN: We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). RESULTS: Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. CONCLUSION: Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

Changing from a Western to a Mediterranean-style diet does not affect iron or selenium status: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) 1-year randomized clinical trial in elderly Europeans.

BACKGROUND: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. OBJECTIVES: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. METHODS: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65-79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. RESULTS: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. CONCLUSIONS: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier.

Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood-brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 µM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd.

Intestinal epithelial barrier functions in ageing.

The intestinal epithelial barrier protects the mucosa of the gastrointestinal (GI)-tract and plays a key role in maintaining the host homeostasis. It encompasses several elements that include the intestinal epithelium and biochemical and immunological products, such as the mucus layer, antimicrobial peptides (AMPs) and secretory immunologlobulin A (sIgA). These components are interlinked with the large microbial community inhabiting the gut to form a highly sophisticated biological system that plays an important role on many aspects of human health both locally and systemically. Like any other organ and tissue, the intestinal epithelial barrier is affected by the ageing process. New insights have surfaced showing that critical functions, including intestinal stem cell regeneration and regulation of the intestinal crypt homeostasis, barrier integrity, production of regulatory cytokines, and epithelial innate immunity to pathogenic antigens change across life. Here we review the age-associated changes of the various components of the intestinal epithelial barrier and we highlight the necessity to elucidate further the mechanisms underlying these changes. Expanding our knowledge in this area is a goal of high medical relevance and it will help to define intervention strategies to ameliorate the quality of life of the ever-expanding elderly population.

Gender-specific association of body composition with inflammatory and adipose-related markers in healthy elderly Europeans from the NU-AGE study.

OBJECTIVES: The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. METHODS: A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65-79 years) women and men from five European countries of the "New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe" project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-ß1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. RESULTS: BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. CONCLUSIONS: The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. KEY POINTS: • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia.

One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial.

Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 µg/day) would improve innate immune responses in healthy elderly subjects (65-79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov, NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of 122 subjects (61 in the intervention group and 61 in the control group) was used to evaluate ex vivo innate immune response, phenotype of circulating immune cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was calculated for all the parameters analyzed. After adjustment by gender, MedDiet-females with a BMI < 31 kg/m2 had a significant upregulation of circulating CD40+CD86+ cells (OR 3.44, 95% CI 1.01-11.75, P = 0.0437). Furthermore, in all MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes, although not statistically significant of immune-critical parameters including T cell degranulation, cytokine production and co-receptor expression. Overall, our study showed that adherence to an individually tailored Mediterranean-like dietary pattern with a daily low dose of vitamin D3 supplements for 1 year modified a large variety of parameters of immune function in healthy, elderly subjects. We interpreted these data as showing that the MedDiet in later life could improve aspects of innate immunity and thus it could aid the design of strategies to counteract age-associated disturbances. Clinical Trial Registration: clinicaltrials.gov, NCT01754012.