A higher daily intake of fruits and vegetables in healthy elderly is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables, but the impact on cognitive performance is unclear. Healthy community dwellers (45 to 102 years old, n=193) underwent cognitive testing and blood withdrawal for the measurement of antioxidant micronutrients and biomarkers of oxidative stress as well as administration of a food frequency questionnaire to assess the daily intake of fruits and vegetables (high intake HI, low intake LI). Ninety-four subjects of the HI group had significantly higher cognitive test scores, higher levels of carotenoids, alpha- and gamma-tocopherol as well as lower levels of F2 alpha isoprostanes than the 99 subjects of the LI group. Cognitive scores were directly correlated with blood levels of alpha-tocopherol and lycopene and negatively correlated with F2 alpha isoprostanes and protein carbonyls. The results were independent of age, gender, body mass index, education, total cholesterol, LDL- and HDL-cholesterol, triglycerides, and albumin. Healthy subjects of any age with a high daily intake of fruits and vegetables have higher antioxidant levels, lower levels of biomarkers of oxidative stress, and better cognitive performance than healthy subjects of any age consuming low amounts of fruits and vegetables. Modification of nutritional habits aimed at increasing intake of fruits and vegetables should be encouraged to lower prevalence of cognitive impairment in later life.

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age-and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and a-carotene. Protein carbonyls were inversely correlated with g-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life. Ageing: Antioxidants: Nutrition: PreventionIn developed countries, it is estimated that the percentage of subjects aged 60 years and older will increase from 19 % currently to almost 40 % in year 2050 (Tinker, 2002). Important with this trend is that the older population is itself ageing: according to the US Census Bureau, the group of very old people (aged 80 years and older) is projected to grow as much as eight to ten times on the global scale between 1950 and 2050. Most chronic diseases manifest in this later stage of life. Until the 1970s, it was thought that disease risk could not significantly increase after a certain advanced age. Therefore, there should be no benefit in changing habits including diet after 80 years of age (Lasheras et al. 2000). To date it is well known that the incidence of several age-related and nutrition-dependent degenerative diseases keeps increasing even in the eldest portion of the population.Previous epidemiologic studies have consistently shown that diet has been implicated in the incidence of six out of ten of the leading causes of death of Americans (Department of Health and Human Services, 1988), and that it plays a crucial role in the prevention of age-related chronic diseases (DarntonHill et al. 2004) as well as in the control of cardiovascular risk factors such as LDL cholesterol (Djoussé et al. 2004). Bioactive compounds like antioxidants, mostly contained in fruits and vegetables (Lampe, 1999), play a particularly important role in the protection against oxidative and nitrative stresses. These processes have been associated with the ageing process and the pathophysiology of age-related illne...

Alterations of the intracellular ubiquitin-proteasome pathway are found in neurodegenerative and inflammatory disorders of the central nervous system, as well as in its malignancies. Inhibitory substrates of the proteasomes represent promising approaches to control autoimmune inflammations and induction of apoptosis in cancer cells. Extracellular circulating proteasomes are positively correlated to outcome prognosis in hematogenic neoplasias and the outcome in critically ill patients. Previously, we reported raised levels of proteolytic active 20S proteasomes in the extracellular alveolar space in patients with acute respiratory distress syndrome (ARDS). For the cerebrospinal fluid, we assumed that extracellular circulating proteasomes with enzymatic activity can be found, too. Cerebrospinal fluid (CSF) samples of twenty-six patients (14 females, 12 males), who underwent diagnostic spinal myelography, were analyzed for leukocyte cell count, total protein content, lactate and interleukine-6 (Il-6) concentrations. CSF samples were analyzed for concentration and enzymatic activity of extracellular 20S proteasomes (fluorescenic substrate cleavage; femtokatal). Blood samples were analyzed with respect to concentration of extracellular circulating proteasomes. Choroidal plexus was harvested at autopsies and examined with immunoelectron microscopy (EM) for identification of possible transportation mechanisms. Statistical analysis was performed using SPSS (18.0.3). In all patients, extracellular proteasome was found in the CSF. The mean concentration was 24.6 ng/ml. Enzymatic activity of the 20S subunits of proteasomes was positively identified by the fluorescenic subtrate cleavage at a mean of 8.5 fkat/ml. Concentrations of extracellular proteasomes in the CSF, total protein content and Il-6 were uncorrelated. Immunoelectron microscopy revealed merging vesicles of proteasomes with the outer cell membrane suggestive of an exozytic transport mechanism. For the first time, extracellular circulating 20S proteasome in the CSF of healthy individuals is identified and its enzymatic activity detected. A possible exozytic vesicle-bond transportation mechanism is suggested by immunoelectron microscopy. The present study raises more questions on the function of extracellular proteasome in the CSF and encourages further studies on the role of extracellular protesomes in pathological conditions of the central nervous system (tumor lesions and inflammatory processes).

Proteasomes are important proteolytic complexes for the processing of endogenous antigen presentation by major Rationale: histocompatibility complex (MHC) class I molecules. These multi-catalytic complexes participate in cell proliferation, differentiation, apoptosis, and cytokine modulation. Low molecule weight protein (LMP) 2 and LMP7 are IFN-γ-inducible and MHC-II-encoded β subunits which can incorporate into the constitutive 20S proteasome and turn it to immunoproteasomes with alterations of catalytic properties. This study aimed to compare the expressions of LMP2 and LMP7 in alveolar macrophages (AMs) of hypersensitivity pneumonitis (HP) and sarcoidosis.BAL cells were collected from 24 patients: 11 HP (8 acute/subacute, 3 chronic) and 13 sarcoidosis (9 inactive, 4 active), and 9 Methods: control subjects. Immunocytochemistry (ICC) was used to stain the cells with monoclonal antibodies against LMP2 and LMP7 (Biotrend Chemikalien GmbH, Koeln, Germany). Proportions of LMP2+ and LMP7+ AMs were calculated and levels of LMP2 and LMP7 proteins in AMs were estimated semi-quantitatively by an intensity-associated score system.The positive rates and the scores of LMP7 expressed in AMs of HP patients were both markedly increased compared with sarcoid Results: patients (p<0.01) and controls (p<0.05), while there were no differences between sarcoid patients and controls (p>0.05) ( Table 1). The positive rates and scores of LMP7 of AMs correlated with increased percentages of CD8+ T cells (r=0.4, p<0.05), decreased percentages of macrophages (r=-0.5, p<0.05) and worse pulmonary function tests (p<0.05) in these granulomatous patients. The positive rates and scores of LMP2 expressed in AMs were not significantly different between patients with HP, sarcoidosis, and controls (all p>0.05). The positive rates and scores of LMP7 in AMs correlated with the values of LMP2 (r=0.6, p<0.01) in granulomatous patients.The expression of immunoproteasomal LMP7, but not LMP2, was amplified in HP compared with controls and sarcoidosis, Conclusion: which suggests that LMP7 may be involved in the pathogenesis of HP. Inhibitors of LMP7 may be a new approach to the treatment of this disease.Positive rates (PRs) and scores of immunosubunits in AMs of control, sarcoidosis and HP groups Table 1. LMP2 LMP7 PR (%) Score PR (%) Score control 75±27 95±45 56±26 62±35 sarcoidosis 68±34 93±57 42±40 51±54 HP 89±9 112±21 85±28* ‡ 115±45* ‡ * vs. control: p<0.05 ‡ vs. sarcoidosis: p<0.01