There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon cancer, we evaluated clock gene and estrogen receptor (ER) alpha/beta expression in colon cancer cells of primary colorectal tumors and adjacent normal colon mucosa (NM) by real-time RT-PCR. Analysis of gene expression in G(2) and G(3) colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G(2): 0.52-fold; P = n.s. and G(3): 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G(2) tumors as compared with NM (female: 0.38-fold; P = 0.004 vs. male: 0.73-fold; P = n.s.). Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G(2) and G(3) tumors (G(2): 0.32-fold; P = 0.003 and 0.27; P = 0.001). No significant gender specific differences of ER-beta reduction in tumors were observed. A significant correlation between the decrease of Per1 and ER-beta in colorectal tumors (r = 0.61; P < 0.001) was found. No changes in gene expression were detected for ER-alpha and Per2. Our data demonstrate a correlated decrease of Per1 and ER-beta in colorectal tumors, mediated probably by epigenetic mechanisms. The observed gender differences in the expression of CLOCK and Per1 in G(2) tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis.

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In summary, we have established a reliable set of reference data for hormonal, hematological, and clinical chemistry analytes for elderly subjects. These values will be very useful for our future attempts to correlate disease states and aging processes with metabolic factors.

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RBP4 plays a role in biological mechanisms that are responsible for insulin resistance and development of type 2 diabetes.

Globally, cardiovascular diseases (CVDs) are the number one cause of all mortalities. Of these deaths, 7.6 million are due to heart attacks, and 5.7 millions are due to stroke. The Vienna Transdanube Aging Study (VITA), a population-based cohort study, enabled us to evaluate associations between the known major risk factors for cerebrovascular and CVDs and their appearance beyond age 75 years. Using a single birth cohort, age was excluded as confounding factor. In the baseline investigations in the Danube Hospital, 606 individuals took part and were examined completely at baseline. After 60 months, 508 patients were re-examined. Each participant underwent an indepth investigation with the duration of 7 h, including neuropsychological testing, as well as analyses of biochemical, clinical chemical and genetic parameters, and magnetic resonance imaging (MRI) of the brain. In the present study, only a history of cerebral and cardiovascular events at the baseline or smoking was associated significantly with the appearance of CVDs. In a multiple model both risk factors-history of cerebral and cardiovascular events at the baseline (p = 0.0003, OR 2.36, 95% CI 1.49-3.76) and smoking (p = 0.0005, OR 1.57, 95% CI 1.22-2.03)-remained significant. However, the predictive value of this assessment model was low. The rescaled r² of the model was 0.088. A significant correlation was found only between exposure to cigarette smoke or a history of previous CVDs, such as stroke or myocardial infarction. Smoking or earlier CVDs greatly increase the risk for further cerebral and cardiovascular events in persons after 75 years.

Clinical chemical reference values for older persons are sparse and mostly intermixed with those for younger persons. We had a unique opportunity to obtain blood samples from volunteers who were 75 years old and living in two districts of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain reference intervals for 120 apparently healthy 75-year-old participants for pro-brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in patients with heart failure and as a prognostic marker in acute coronary syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids in the prognosis of ventricular systolic dysfunction and helps to differentiate between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men and women in our cohort was calculated as 98 pg/ml, comparing favorably with reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes acutely decompensated heart failure. Our calculated 97.5 percentile was slightly higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons (198 and 222 pg/ml for men and women, respectively) revealing the influence of age on this parameter. Because of its high tissue-specificity, cardiac troponin T is a cardiospecific, highly sensitive marker for myocardial damage. However, the troponin T concentrations in the plasma specimens from this cohort were all below the detection limit of 0.01 ng/ml, preventing any further data handling.

The Vienna Transdanube Aging (VITA) study searches for early markers of Alzheimer's disease (AD) by examining the mental status in a community-based cohort of 606, 75-years old volunteers that are then related to various clinical and genetic analyses. To determine whether mutations in mtDNA are involved in expression of AD, the mtDNA of 79 "control" participants is screened for alterations by sequencing of "hot-spot-regions". This study on mtDNA mutations has eliminated the influence of aging on the occurrence of mtDNA alterations by sequencing samples from persons at the age of exactly 75 years. Thus, our cohort reveals a snap-shot of mitochondrial sequences of elderly persons. So far, a high percentage (56%) of persons with known or unknown mutations in the fragments analyzed were found. These data will be compared in due time to a cohort of participants with proven late-onset AD.