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• IL-1β, IL-6 and TNF-α seem not to be involved in the onset of PDF or TIRD. • Predialysis IL-10 levels correlate positively but counterintuitively with PDF severity. • PDF significantly correlates with TIRD. The aetiology of postdialysis fatigue (PDF), an intermittent but debilitating fatigue occurring after haemodialysis (HD) treatment, is still unclear. In other inflammatory diseases, increasing evidence points toward the involvement of the immune system in the onset of fatigue symptoms. Altered serum levels of inflammatory cytokines have also been shown in HD patients. Therefore, we investigated whether pre- and postdialysis serum levels of pro- and anti-inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α and IL-10) or their intradialytic changes (if any) were related to PDF or the time HD patients reported needing to recover from HD treatment (TIRD). Serum levels of IL-1β, IL-6, TNF-α and IL-10 were measured immediately before and after HD in 45 patients using commercially available kits on an ELLA™ automated immunoassay system. The presence and severity of PDF as well as TIRD duration were assessed by self-report measures. Seventy-four percent of patients reported PDF, with a median PDF severity index of 3.30 [IQR: 3.00–4.30] on a scale from 1 to 5. Median TIRD was 120 min [IQR: 60–480]. PDF severity correlated strongly with TIRD, r s = 0.85, p < 0.001. Only predialysis levels of IL-10 significantly and positively correlated with PDF severity (r s = 0.43, p = 0.003). Findings of the present study do not support the involvement of the immune system in the onset of PDF or the time patients needed to recover from HD treatment. A positive, but counterintuitive relationship was found between predialysis levels of anti-inflammatory IL-10 and PDF severity, which warrants further research. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO. [ABSTRACT FROM AUTHOR]

• Serum Endotoxin and IL-6 levels are significantly correlated with fatigue in HD. • Serum endotoxin levels and depressive symptoms independently predict fatigue in HD. • Serum endotoxin levels and depressive symptoms explain 31% of variance in fatigue. Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies. [ABSTRACT FROM AUTHOR]

The article provides information on the results of a study on the inducement of carnitine depletion through decreased Octn2 and Atb0+ expression in a rat colonocytes model of experimental colitis. It states that carnitine uptake was reduced when sodium was superseded by N-methylglucamine. The role of carnitine in the regulation of cell metabolic fluxes has been presented through a finding that an increase of acetyl-coenzyme A was limited to the mitochondrial compartment of colonocytes.

Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were included. Older adults were classified into high–functioning (HF) and low–functioning (LF) groups according to their Short Physical Performance Battery score. Vastus lateralis muscle biopsies were assayed for total iron content, expression of 8-oxoguanine and DNA glycosylase (OGG1), 3-nitrotyrosine (3-NT) levels, and mitochondrial DNA (mtDNA) content and damage. Circulating ferritin and hepcidin levels were also quantified. Muscle iron levels were greater in the old group. Protein expression of transferrin receptor 1, Zrt-Irt-like protein (ZIP) 8, and ZIP14 were lower in old participants. Circulating levels of ferritin, hepcidin, interleukin 6 (IL6), and C-reactive protein were higher in the old group. Old participants showed lower mtDNA content and greater mtDNA damage. OGG1 protein expression declined with age, whereas 3-NT levels were greater in old participants. Finally, a negative correlation was determined between ZIP14 expression and circulating IL6 levels in LF older adults. None of assayed parameters differed between HF and LF participants. Our findings suggest that muscle iron homeostasis is altered in old age, which might contribute to loss of mtDNA stability. Muscle iron metabolism may therefore represent a target for interventions against muscle aging. [ABSTRACT FROM AUTHOR]

Frailty encompasses several domains (i.e., metabolic, physical, cognitive). The multisystem derangements underlying frailty pathophysiology, its phenotypic heterogeneity, and the fluctuations of individuals across severity states have hampered a comprehensive appraisal of the condition. Circulating biomarkers emerged as an alleged tool for capturing this complexity and, as proxies for organismal metabolic changes, may hold the advantages of: 1) supporting diagnosis, 2) tracking the progression, 3) assisting healthcare professionals in clinical and therapeutic decision-making, and 4) verifying the efficacy of an intervention before measurable clinical manifestations occur. Among available analytical tools, metabolomics are able to identify and quantify the (ideally) whole repertoire of small molecules in biological matrices (i.e., cells, tissues, and biological fluids). Results of metabolomics analysis may define the final output of genome-environment interactions at the individual level. This entire collection of metabolites is called "metabolome" and is highly dynamic. Here, we discuss how monitoring the dynamics of metabolic profiles may provide a read-out of the environmental and clinical disturbances affecting cell homeostasis in frailty-associated conditions. Unlabelled Image • The heterogeneity of frailty hampers a comprehensive appraisal of the condition. • Biomarkers have been proposed in place of deficit indices for investigating frailty. • Metabolomics have emerged as a strategy for capturing frailty complexity. • Patterns of metabolic markers characterize frailty-related conditions. • Metabotype analysis may assist in devising tailored strategies against frailty. [ABSTRACT FROM AUTHOR]

While mitochondrial dysfunction is acknowledged as a major feature of aging, much less is known about the role of mitochondria in extended longevity. Livers from aged (28-month-old) and extremely aged (32-month-old) rats were analyzed for citrate synthase activity, mitochondrial transcription factor A (TFAM) amount, mitochondrial DNA (mtDNA), and 4.8 Kb "common deletion" contents. None of the assayed parameters differed significantly between age groups. TFAM-binding to mtDNA and the incidence of 8-oxo-deoxyguanosine in specific mtDNA regions, encompassing the origins of mtDNA replication (D-loop and Ori-L) and the 16-bp long direct repeat 1 (DR1) of the 4.8 Kb deletion, were determined. A decrease in TFAM binding was unveiled at all regions in extremely aged in comparison with aged rats. Reduced incidence of oxidized purines at all assayed regions was detected in 32-month-old rats compared with the 28-month-old group. A significant positive correlation between the incidence of 8-oxo-deoxoguanosine and TFAM-bound mtDNA was found at D-Loop and Ori-L regions only in 28-month-old rats. The absence of such correlation in 32-month-old rats indicates a different, fine-tuned regulation of TFAM binding in the two age groups and supports the existence of two different paces in aging and extended aging. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging. [ABSTRACT FROM AUTHOR]