Relationship between body composition changes and changes in physical function and metabolic risk factors in aging

PURPOSE OF REVIEW: Several body composition changes are known to occur with aging. The purpose of this review is to evaluate recent literature examining body composition changes with aging and how these relate to changes in physical function and metabolic risk. RECENT FINDINGS: Cross-sectional and longitudinal studies have observed increases in fat mass and decreases in muscle mass or lean tissue mass in older adults, often in the absence of differences or changes in body weight. Cross-sectional studies have also reported increases in intramyocellular lipid and liver fat in older versus younger adults and related changes in body composition with changes in physical function and metabolic risk, but few longitudinal data are available. Furthermore, most longitudinal studies lack precise methods of assessing body fat distribution and muscle and organ quality, resulting in a lack of detailed and precise information on body composition changes with aging and their relationship to health. SUMMARY: Research to date has outlined a need for more detailed body composition measurements of aging adults. Absence of change in a total body compartment may mask a change in subcompartments that may impact health. Furthermore, intervention studies to determine ways to maintain body composition are consistent with healthy living throughout the aging process.     

In vitro evidence and age-related changes for nicotinic but not muscarinic acetylcholine receptors in the central nervous system of Sepia officinalis

Binding putative muscarinic ([3H]-NMS and [3H]-QNB) or nicotinic ([3H]-cytisine) acetylcholine receptors was quantitatively studied through the use of in vitro binding experiments on either membrane preparations or brain sections of juvenile (3 months), mature (15 months) or senescent (23 months) cuttlefish. No specific binding could be detected with muscarinic receptor ligands under any of the experimental conditions employed (ligand concentrations, buffers, ionic charges, types of tissue, i.e., brain sections or membrane preparations). On the other hand, [3H]-cytisine demonstrated a specific and saturable binding with a single class of high affinity binding sites (Kd of 2.6-34.6 nM; Bmax of 128-1682 fmol/mg tissue equivalent, depending on the central structure). This binding was found to be heterogeneous throughout the central regions (optic lobe>pedal lobe; superior frontal lobe>...precommissural lobe; vertical lobe>...anterior basal lobe; subvertical lobe; inferior frontal lobe; median basal lobe). These results question the existence of muscarinic-like receptors in the cuttlefish brain, or at least of a pharmacological dissimilarity from vertebrate muscarinic receptors. In contrast, nicotinic-like receptors are widely present; interestingly, their density was found to be significantly reduced in most nervous central lobes of senescent cuttlefish when compared with mature animals. The most significant decrease (-71%) was found in the anterior part of the superior frontal lobe, which is involved in visual learning; this might be related to the changes, previously demonstrated, in cholinergic neurons in this lobe in the course of aging.     

Exosomal-like vesicles are present in human blood plasma

Exosomes are small membrane vesicles (50-90 nm in diameter) secreted by most hematopoietic cells. We provide here the first evidence for the presence of exosomes in vivo, in the blood. Plasma samples of all healthy donors tested (n = 15) contain vesicles that are similar in shape, size and density to the previously described exosomes. They were clearly identified by electron microscopy after isolation by differential ultracentrifugation or immunoisolation with CD63-coated latex beads. We performed their biochemical characterization by western blot analysis and by flow cytometry after vesicle adsorption onto latex beads using a panel of mAbs. We observed that these plasma-derived vesicles contain tetraspanin molecules such as CD63, CD9, CD81 as well as class I and class II MHC molecules and Lamp-2 (i.e. proteins that are known to be enriched in exosomes). In addition, these vesicles float on sucrose gradient at a density similar to exosomes. Our results demonstrate that blood is a physiological fluid for exosome circulation in the body, suggesting their role in cell-cell or organ-organ communications as carriers for molecules that need to reach distant cell targets.     

The MAP kinase pathway mediates transcytosis induced by TNF-alpha in an in vitro blood-brain barrier model

Cerebral capillary endothelial cells constitute the blood-brain barrier (BBB). In these highly specialized cells, transcellular transports rarely occur, and the presence of tight junctions between them leads to a low paracellular permeability. In order to understand the functions of this barrier, an in vitro model of the BBB has been developed and consists in a co-culture of primary cerebral capillary endothelial cells and glial cells. When these endothelial cells are subjected to an inflammatory agent, such as tumor necrosis factor-alpha (TNF-alpha), in vitro BBB permeability is increased, as indicated by the increase in holotransferrin transcytosis. However, no significant change in the paracellular permeability is observed. In order to understand the molecular mechanisms that underlie these transcytosis processes, we investigated the implication of the mitogen-activated protein kinase (MAPK) signalling pathway, as TNF-alpha is known to activate this kinase family. In the present study, an increase in the activation of p42-44 MAPK is observed after TNF-alpha treatment. Holotransferrin transcytosis as well as p42-44 MAPK activation are inhibited after addition of a p42-44 MAPK pathway inhibitor (UO126) during TNF-alpha challenge. These data suggest that the MAPK pathway is involved in the transcytosis regulation in endothelial cells from an in vitro BBB model.     

Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual

OBJECTIVE: To determine the prevalence rates and likelihood of the metabolic syndrome and its individual components in normal-weight and slightly overweight individuals (BMI 18.5-26.9 kg/m(2)). RESEARCH DESIGN AND METHODS: There were a total of 7,602 adult participants of the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey. Prevalence and odds ratios (ORs) of the metabolic syndrome, defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, were computed according to 2.0- to 2.5-unit increments in BMI. RESULTS: Depending on ethnicity and sex, the prevalence of the metabolic syndrome increased in a graded fashion from 0.9-3.0% at BMI 18.5-20.9 kg/m(2) to 9.6-22.5% at BMI 25.0-26.9 kg/m(2). Compared with men with BMI 18.5-20.9 kg/m(2), the odds for the metabolic syndrome were 4.13 (95% CI 1.57-10.87) for men with BMI 21-22.9 kg/m(2), 5.35 (2.41-11.86) for men with BMI 23-24.9 kg/m(2), and 9.08 (4.23-19.52) for men with BMI 25-26.9 kg/m(2) after controlling for age, ethnicity, education, income, physical activity, smoking status, and alcohol and total fat, saturated fat, carbohydrate, and fiber intakes. The corresponding ORs in women were 4.34 (2.08-9.07), 7.77 (3.95-15.26), and 17.34 (9.29-32.38). CONCLUSIONS: Individuals in the upper normal-weight and slightly overweight BMI range have a relatively high prevalence and are at increased risk of having the metabolic syndrome. Therefore, screening in individuals with normal or slightly elevated BMI is important in the prevention of diabetes and cardiovascular disease.     

Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardio-vascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.     

Infection of human astrocytes and glioblastoma cells with<Emphasis Type="Italic"> Toxoplasma gondii</Emphasis>: monocyte chemotactic protein-1 secretion and chemokine expression in vitro

In immunocompromised hosts, disruption of toxoplasmic cysts and conversion from bradyzoites to tachyzoites occur in brain. In these areas, infiltrates of mononuclear cells are observed. In the murine toxoplasmosis model, recent data suggest that chemokines may play a role in leukocyte recruitment in the central nervous system (CNS). This study analyzed the monocyte chemotactic protein-1 (MCP-1) secretion and chemokine expression after Toxoplasma gondii infection of human astrocytes, glioblastoma cells (U373) and fibroblasts (MRC5) in vitro. T. gondii infection of these CNS cells, astrocytes and glioblastoma cells significantly increased MCP-1 secretion, particularly for astrocytes. In our cellular models, the pattern of chemokine gene expression is dominated by MCP-1 expression. MCP-1 mRNAs were also quantified by real-time-PCR (LightCycler). The behavior of cells studied after T. gondii infection was different (invasion and growth) and the cell mechanisms of chemokine regulation could be dependent on the type of cells infected, while MCP-1 may contribute to the cell recruitment during human cerebral reactivation of T. gondii.