Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies.
Cellular processes function through multistep pathways that are reliant on the controlled association and disassociation of sequential protein complexes. While dynamic action is critical to propagate and terminate work, the mechanisms used to disassemble biological structures are not fully understood. Here we show that the p23 molecular chaperone initiates disassembly of protein-DNA complexes and that the GCN5 acetyltransferase prolongs the dissociated state through lysine acetylation.
Caloric/dietary restriction (CR/DR) can promote longevity and protect against age-associated disease across species. The molecular mechanisms coordinating food intake with health-promoting metabolism are thus of significant medical interest. We report that conserved Caenorhabditis elegans microRNA-80 (mir-80) is a major regulator of the DR state.
Journal of Child Psychology and Psychiatry, and Allied Disciplines
Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene-environment correlations.
Alzheimer' s disease (AD) is the most common form of dementia causing an increasing emotional and economical burden to our societies. Although much progress has been made regarding the molecular mechanisms that underlie AD pathogenesis effective therapies are not available yet. The emerging field of neuroepigenetics has provided evidence that de-regulation of epigenetic processes play a role in AD.
Alzheimer's disease is associated with metabolic deficits and reduced mitochondrial function, with the latter due to the effects of oligomeric amyloid beta peptide (A?O) on the respiratory chain. Recent evidence has demonstrated reduction of epigenetic markers, such as DNA methylation, in Alzheimer's disease. Here we demonstrate a link between metabolic and epigenetic deficits via reduction of mitochondrial function which alters the expression of mediators of epigenetic modifications.
Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective.
Diabetes is a proinflammatory state. We have previously shown increased monocyte proinflammatory cytokines in patients with Type 1 and Type 2 diabetes. High glucose induces proinflammatory cytokines via epigenetic changes. Curcumin, a polyphenol responsible for the yellow color of the spice turmeric, is known to exert potent anti-inflammatory activity in vitro. Recent studies indicate that it may regulate chromatin remodeling by inhibiting histone acetylation.
Inhibitors of histone acetyltransferases (HATs) are perceived to treat diseases like cancer, neurodegeneration, and AIDS. On the basis of previous studies, we hypothesized that Cys(1438) in the substrate binding site could be targeted by Δ(12)-prostaglandin J(2) (Δ(12)-PGJ(2)), a cyclopentenone prostaglandin (CyPG) derived from PGD(2). We demonstrate here the ability of CyPGs to inhibit p300 HAT-dependent acetylation of histone H3.
Proceedings of the National Academy of Sciences of the United States of America
Transcriptional control of metabolic circuits requires coordination between specific transcription factors and coregulators and is often deregulated in metabolic diseases. We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial function and in energy expenditure as a consequence of activation of PGC-1alpha.