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Abstract Decline in immune function with age has been studied extensively, but approaches to immune restoration have been hampered by the lack of simple methods of identifying individuals whose immune system is in decline. Our approach has been to identify individuals whose immune decline has led to a loss of control of common latent viral infections and their consequent reactivation. Viruses excreted in urine were detected and quantified and we believe this approach could provide a 'surrogate marker' for identifying immune compromised individuals. Here we report the detection of human herpes virus (HHV) 5, 6a, 6b and 7 in the urine of healthy individuals over a wide age range and their correlation with T cell receptor excision circle (TREC) data. The results did not show a clear correlation between TREC values and the detection of individual specific viruses or viral load values when measured singly. However, a correlation was found between low TREC values and the detection of several different human herpes viruses in the urine in males. We present evidence suggesting that for males, the detection of three or more different human herpes viruses in the urine could identify individuals with declining immune function as evidenced by their significantly lower TREC levels.

Summary: Recent studies have shown that elevated concentrations of unconjugated bilirubin (UCB) may be a protective host factor against the development of noncommunicable diseases (NCDs), whereas low levels of UCB are associated with the opposite effect. The results of this European study, in which 2,489 samples were tested for their UCB concentration using high-performance liquid chromatography (HPLC) and additional data from the MARK-AGE database were used for analysis, provide further evidence that elevated UCB concentrations are linked to a lower risk of developing NCDs and may act as a predictive marker of biological aging as individuals with elevated UCB concentrations showed favorable outcomes in metabolic health and oxidative-stress-related biomarkers. These findings underline the significance of studying individuals with moderate hyperbilirubinemia and investigate UCB routinely, also in the setting of aging, since this condition affects millions of people worldwide but has been underrepresented in clinical research and practice until now.

The presence of circulating microbiome in blood has been reported in both physiological and pathological conditions, although its origins, identities and function remain to be elucidated. This study aimed to investigate the presence of blood microbiome by quantitative real-time PCRs targeting the 16S rRNA gene. To our knowledge, this is the first study in which the circulating microbiome has been analyzed in such a large sample of individuals since the study was carried out on 1285 Randomly recruited Age-Stratified Individuals from the General population (RASIG). The samples came from several different European countries recruited within the EU Project MARK-AGE in which a series of clinical biochemical parameters were determined. The results obtained reveal an association between microbial DNA copy number and geographic origin. By contrast, no gender and age-related difference emerged, thus demonstrating the role of the environment in influencing the above levels independent of age and gender at least until the age of 75. In addition, a significant positive association was found with Free Fatty Acids (FFA) levels, leukocyte count, insulin, and glucose levels. Since these factors play an essential role in both health and disease conditions, their association with the extent of the blood microbiome leads us to consider the blood microbiome as a potential biomarker of human health.

Recently, Weber et al. published a thorough investigation of the age-dependency of oxidative stress (OS) determined by the steady state concentrations of different compounds - oxidation products and antioxidants - that are in common use as biomarkers of OS in 2207 healthy individuals of the cross-sectional MARK-AGE Project. The correlations among biomarkers were significant but weak. These findings may indicate different manifestations of OS and must further be evaluated. Here, we report a refined analysis of OS based on the above-mentioned original data. We show that malondialdehyde (MDA) appears to be sensitive to both gender and age. It is significantly lower and shows a greater age-dependence in women than in men. The age-dependency of MDA in women arises in a stepwise fashion. The age-dependent slope of the steady state concentration is maximal at the age between 50 and 55 years, indicating that it may be attributed to the change of metabolism in the post-menopause. Interestingly, total glutathione (GSH) decreased with age simultaneously with the increase in MDA.Different biomarkers yield different gender- and age-dependencies. Unlike the concentration of MDA, the concentrations of the other two oxidation products, i.e. protein carbonyls and 3-nitrotyrosine were similar in men and women and appeared to be independent of age in the healthy study population. The analyzed antioxidants exhibited different gender- and age-dependencies. In conclusion, it appears that all the biomarkers assessed here reflect different types of OS and that MDA and GSH reflect the same type of OS. Keywords: Oxidative stress, Age-dependency, Gender-associated differences, Biomarkers