Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer (nfkb1 2/2 mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development. Interventional exercise when applied at a relatively late disease stage was effective at reducing tissue inflammation (liver, lung, and stomach), oxidative damage, and cellular senescence, and it reversed hepatic steatosis and prevented tumor development. Underlying these benefits were transcriptional changes in enzymes driving the conversion of tryptophan to NAD + , this leading to increased hepatic NAD + and elevated activity of the NAD +-dependent deacetylase sirtuin. Increased SIRT activity was correlated with enhanced deacetylation of key transcriptional regulators of inflammation and metabolism, NF-kB (p65), and PGC-1a. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.

Carbohydrate-deficient transferrin (CDT) has been demonstrated to be a marker of prolonged heavy alcohol consumption. We compared this marker with gamma-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV) in alcohol and nonalcohol abusers with liver disease. Our results confirm that the sensitivity of CDT in alcoholics is high, although lower than that of GGT and MCV; however, the specificity of CDT was higher than that of the other two markers. This finding supports the notion that CDT is only partially influenced by the presence of liver damage, whereas increases of GGT and MCV are greatly affected by several factors, including liver damage and drugs. Moreover, we observed that the sensitivity and the specificity of CDT were greater than those of GGT and MCV in younger drinkers.

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non‐coding genome. Recent advances in epigenomic profiling have uncovered non‐coding gene proximal promoters and distal enhancers of transcription genome‐wide. Extension of promoter‐associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3‐BD), is a signature of constitutive expression of cell‐type‐specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3‐BDs over oncogenes is a cancer‐specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super‐enhancers (SE), by proto‐oncogenes results in the presence of H3K4me3‐BDs over the gene body. Therefore, H3K4me3‐BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers.

interacts with the p50 NF-κB subunit via its nuclear localization sequence to constrain inflammatory gene expression. Biochimica et Biophysica Acta:

Nucleotide sequence comparisons of the published cDNAs and genomic sequences coding for the gamma-chain of human fibrinogen revealed several differences. We isolated two independent human cDNA clones, coding for part of this protein and compared their sequences, which are identical with the published relevant data. Our sequence allowed us to solve a conflict for aminoacid 88. All the remaining differences resulting from this comparison occurred in the third position of a codon and did not change codon properties or restriction sites. The level of polymorphism of this gene is discussed, taking into account also the nucleotide differences among all the published relevant data.