AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether ?-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes.
DNA methylation patterns change as individuals grow older, and DNA methylation appears susceptible to modification by the diet. Thus DNA methylation may be a mechanism through which diet can affect aging and longevity. We propose that effects on DNA methylation also contribute to the extension in lifespan observed in response to dietary restriction. Relationships between diet-induced changes in DNA methylation and parallel effects on aging and/or lifespan could, of course, be purely associative.
Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ?-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C.
Caloric restriction (CR) has been extensively documented for its profound role in effectively extending maximum lifespan in many different species. However, the accurate mechanisms, especially at the cellular level, for CR-induced aging delay are still under intense investigation. An emerging technique, recently explored in our laboratory, provides precisely controllable caloric intake in a cultured cellular system that allows real-time observation and quantitative analysis of the impact of CR on the molecular cellular level during the aging processes.
The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase, synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere maintenance in two immortalized human cell lines: the B-cell line JY616 and the T-cell line Jurkat E6-1, and determined whether known inhibitors of retroviral reverse transcriptases could perturb telomere lengths and growth rates of these cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive telomere shortening over several weeks of passaging, after which the telomeres stabilized and remained short.
Proceedings of the National Academy of Sciences of the United States of America
Human fibroblasts whose lifespan in culture has been extended by expression of a viral oncogene eventually undergo a growth crisis marked by failure to proliferate. It has been proposed that telomere shortening in these cells is the property that limits their proliferation. Here we report that ectopic expression of the wild-type reverse transcriptase protein (hTERT) of human telomerase averts crisis, at the same time reducing the frequency of dicentric and abnormal chromosomes.
Telomerase is a cellular reverse transcriptase that uses part of its integral RNA (called TER) as the template to synthesize telomeric DNA repeats. Vertebrate TERs are thought to share a conserved, highly structured core domain that includes the templating sequence and a pseudoknot, but not all features of the predicted core structure have been verified directly or shown to affect telomerase enzymatic activity. Here, we report a systematic mutational analysis of the core domain (residues 1 to 210) of human telomerase RNA (hTER).
The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase, synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere maintenance in two immortalized human cell lines: the B-cell line JY616 and the T-cell line Jurkat E6-1, and determined whether known inhibitors of retroviral reverse transcriptases could perturb telomere lengths and growth rates of these cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive telomere shortening over several weeks of passaging, after which the telomeres stabilized and remained short.
Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple human cell types: neuroblastoma cells (SHSY5Y), neuronal precursor cells (NT2), differentiated neurons (hNT) and hepatoma cells (HepG2).
Estrogen receptors (ER alpha/ER beta) are expressed in neuronal cells and exhibit a variety of activities in the central nervous system. ER activity is regulated in a ligand-dependent manner and by co-regulatory factors. Caveolin-1 is a recently identified co-activator of ER alpha mediating the ligand-independent activation of this steroid receptor. Here the influence of ERs on caveolin expression in human neuroblastoma SK-N-MC cells as well as in rodent brain was investigated.
