Immunological features beyond CD4/CD8 ratio values in older individuals.

The CD4/CD8 T-cell ratio is emerging as a relevant marker of evolution for many pathologies and therapies. We aimed to explore immunological features beyond CD4/CD8 ratio values in older subjects (>65 years old) who were classified as having lower (<1.4), intermediate (1.4-2), or higher (>2) ratio values. The lower group showed a lower thymic output (sj/ß-TREC ratio) and frequency of naïve T-cells, concomitant with increased mature T-cells. In these subjects, the CD4 T-cell subset was enriched in CD95+ but depleted of CD98+ cells. The regulatory T-cell (Treg) compartment was enriched in CTLA-4+ cells. The CD8 T-cell pool exhibited increased frequencies of CD95+ cells but decreased frequencies of integrin-ß7+ cells. Interestingly, in the intermediate group, the CD4 pool showed greater differences than the CD8 pool, mostly for cellular senescence. Regarding inflammation, only hsCRP was elevated in the lower group; however, negative correlations between the CD4/CD8 ratio and ß2-microglobulin and sCD163 were detected. These subjects displayed trends of more comorbidities and less independence in daily activities. Altogether, our data reveal different thymic output and immune profiles for T-cells across CD4/CD8 ratio values that can define immune capabilities, affecting health status in older individuals. Thus, the CD4/CD8 ratio may be used as an integrative marker of biological age.

Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (ß), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-ß (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline.

Evaluation of the effect of dietary virgin olive oil on blood pressure and lipid composition of serum and low-density lipoprotein in elderly type 2 diabetic subjects.

Dietary virgin olive oil may help to reduce blood pressure in hypertensive individuals, but little is known about the effect on type 2 diabetic patients. For the present study, 17 type 2 diabetic elderly subjects and 23 healthy elderly controls received a diet rich in virgin olive oil for 4 weeks. Blood pressure, biochemical parameters, low-density lipoprotein (LDL), and oxidized LDL lipids and fatty acids were measured. Systolic blood pressure was reduced after virgin olive oil consumption in both controls and diabetic patients. Although the biochemical parameters were not modified, the intervention protected LDL from oxidation and restored the levels of dihomo-gamma-linolenic acid (20:3, n-6) in serum cholesterol esters and phospholipids of diabetic patients. In conclusion, the present study provides new evidence of the effects of dietary virgin olive oil on blood pressure and LDL oxidation in type 2 diabetics. It is likely that the components responsible for the observed effects are the monounsaturated fatty acids and the presence of antioxidants in the oil, but this needs further investigation.

G protein-coupled receptor systems and their lipid environment in health disorders during aging.

Cells, tissues and organs undergo phenotypic changes and deteriorate as they age. Cell growth arrest and hyporesponsiveness to extrinsic stimuli are all hallmarks of senescent cells. Most such external stimuli received by a cell are processed by two different cell membrane systems: receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). GPCRs form the largest gene family in the human genome and they are involved in most relevant physiological functions. Given the changes observed in the expression and activity of GPCRs during aging, it is possible that these receptors are directly involved in aging and certain age-related pathologies. On the other hand, both GPCRs and G proteins are associated with the plasma membrane and since lipid-protein interactions regulate their activity, they can both be considered to be sensitive to the lipid environment. Changes in membrane lipid composition and structure have been described in aged cells and furthermore, these membrane changes have been associated with alterations in GPCR mediated signaling in some of the main health disorders in elderly subjects. Although senescence could be considered a physiologic process, not all aging humans develop the same health disorders. Here, we review the involvement of GPCRs and their lipid environment in the development of the major human pathologies associated with aging such as cancer, neurodegenerative disorders and cardiovascular pathologies.

Virgin olive oil reduces blood pressure in hypertensive elderly subjects.

BACKGROUND & AIMS: Hypertension is one of the most important risk factors for coronary heart disease. Recent studies have pointed out the possibility that virgin olive oil (VOO) may lower blood pressure in hypertensive (HT) subjects. However, until the date there is scarce information regarding elderly people. The present study was designed to assess the effect of dietary VOO on blood pressure in medically treated hypertensive elderly patients. METHODS: 31 medically treated HT elderly patients and 31 normotensive (NT) elderly volunteers participated in a randomized sequential dietary intervention. Subjects consumed diets enriched in sunflower oil (SO) or VOO for 4 weeks each with a 4-week washout period between them. RESULTS: VOO reduced total and LDL-cholesterol in NT but not in HT (P < 0.01) and the concentrations were lower than in the group consuming SO. In contrast, no significant differences were found in the levels of tocopherols among the groups studied. Iron-induced oxidation of LDL resulted in a complete loss of monoacylglycerols (MG) and diacylglycerols (DG) and a reduction in triacylglycerols (TG) (60-80%), which was found to be greater in HT (P < 0.01) with no effect of diet. VOO consumption normalized systolic pressure in the HT group (136 +/- 10 mmHg) compared to SO (150 +/- 8 mmHg). CONCLUSION: Dietary VOO proved to be helpful in reducing the systolic pressure of treated HT elderly subjects. However, a greater resistance to the lowering effect of VOO of total and LDL-cholesterol and a greater susceptibility to TG oxidation was detected in these patients.

Plasma lipid modifications in elderly people after administration of two virgin olive oils of the same variety (Olea europaea var. hojiblanca) with different triacylglycerol composition.

In the present study we examined whether two virgin olive oils (VOO1 and VOO2), of the same variety (Olea europaea var. hojiblanca with a similar composition of minor components but differing in the content of triacylglycerol molecular species, had different effects on blood pressure and plasma lipid levels in a healthy elderly population. Thirty-one participants, aged 84-9 (SD 6.4) years, were asked to participate in the study. No differences were found with regard to blood pressure after both experimental periods (VOO1 and VOO2). However, plasma total cholesterol and LDL-cholesterol were reduced only after VOO1 (P<0.01). The reduction of plasma cholesterol concentrations was related to the incorporation of oleic acid into plasma cholesteryl esters and phospholipids strongly correlated with plasma total cholesterol and LDL-cholesterol levels in all experimental periods studied (r2>0.418, P<0.07), except for phospholipids in VOO1 (P=0.130 for total cholesterol and p=0.360 for LDL-cholesterol). These results have demonstrated that blood pressure and plasma lipids can be modified by the consumption of VOO in elderly people, but that the extent of such modification depends on the composition and amount of active minor components and triacylglycerol molecular species.