NaCT (sodium-coupled citrate transporter) is an Na(+)-coupled citrate transporter identified recently in mammals that mediates the cellular uptake of citrate. It is expressed predominantly in the liver. NaCT is structurally and functionally related to the product of the Indy (I'm not dead yet) gene in Drosophila, the dysfunction of which leads to lifespan extension. Here, we show that NaCT mediates the utilization of extracellular citrate for fat synthesis in human liver cells, and that the process is stimulated by lithium.
When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast and the nematode worm Caenorhabditis elegans. In the worm, this extension of lifespan requires the FOXO transcription factor daf-16. Three recent articles focusing on mammalian homologues of Sir2 and FOXO have highlighted the mechanisms that generate this genetic interaction. Mammalian SIRT1 deacetylates FOXO3 and/or FOXO4, thus attenuating FOXO-induced apoptosis and potentiating FOXO-induced cell-cycle arrest.
Studies in a variety of model organisms indicate that nutrient signaling is tightly coupled to longevity. In nutrient replete conditions, organisms develop, grow, and age quickly. When nutrients become sparse as with dietary restriction, growth and development decline, stress response pathways become induced and organisms live longer. Considerable effort has been devoted to understanding the molecular events mediating lifespan extension by dietary restriction.
Journal of Genetics and Genomics = Yi Chuan Xue Bao
CoQ is an essential electron carrier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes (COQ1-9) involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis.
Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD(+)) as a cofactor linking their activity to the cellular metabolic status. Originally found in yeast, Sir2 was discovered as a silencing factor and has been shown to mediate the effects of calorie restriction on lifespan extension.
Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes that are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displays higher levels of NADPH.
An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues.
Biochemical and Biophysical Research Communications
Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes. Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging. To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system.
BACKGROUND: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies.
Multi-cellular organisms need to successfully link cell growth and metabolism to environmental cues during development. Insulin receptor-target of rapamycin (InR-TOR) signalling is a highly conserved pathway that mediates this link. Herein, we describe poly, an essential gene in Drosophila that mediates InR-TOR signalling. Loss of poly results in lethality at the third instar larval stage, but only after a stage of extreme larval longevity.