Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete.
Black rice is rich in anthocyanin antioxidants. The present study investigated the lifespan-prolonging activity of black rice extracts (BREs) and its effect on gene expressions of CuZnSOD (SOD1), MnSOD (SOD2), catalase (CAT), methuselah (Mth) and Rpn11 involved in the antioxidant system and ageing of fruit flies. The OR wild type fly was maintained on a control diet or two experimental diets containing 10 mg ml(-1) BRE (BRE10) or 30 mg ml(-1) BRE (BRE30).
Aging, the major cause of several ailments has led to intense exploration of potential drugs that delay aging and its associated effects. We mined the information on traditional Indian medicines and identified an iridoid, 10-O-trans-p-Coumaroylcatalpol (OCC), a major ingredient of Premna integrifolia Linn. (syn: Premna serratifolia). OCC forms an important constituent of famous herbal formulation 'Dashmula', a ten herb formulation, commonly used for its various medicinal properties. Employing model system C.
A common thread among conserved life span regulators lies within intertwined roles in metabolism and energy homeostasis. We show that heterozygous mutations of AMP biosynthetic enzymes extend Drosophila life span. The life span benefit of these mutations depends upon increased AMP:ATP and ADP:ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended life span, while AMPK RNAi reduced life span.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Stabilization of the hypoxia-inducible factor (HIF-1) protein extends longevity in Caenorhabditis elegans. However, stabilization of mammalian HIF-1? has been implicated in tumor growth and cancer development. Consequently, for the hypoxic response to benefit mammalian health, we must determine the components of the response that contribute to longevity, and separate them from those that cause harm in mammals. Here, we subject adult worms to low oxygen environments. We find that growth in hypoxia increases longevity in wild-type worms but not in animals lacking HIF-1 or DAF-16.
Studies in mutant, gene knock-out and transgenic mice have demonstrated that growth hormone (GH) signalling has a major impact on ageing and longevity. Growth hormone-resistant and GH-deficient animals live much longer than their normal siblings, while transgenic mice overexpressing GH are short lived. Actions of GH in juvenile animals appear to be particularly important for life extension and responsible for various phenotypic characteristics of long-lived hypopituitary mutants.
Understanding the trade-offs between organisms' life history traits has been a major goal of physiology, ecology and evolution. In the last few decades, two types of intra-specific studies have highlighted the trade-off between growth and longevity. First, diet restriction (DR), as an environmental intervention, has been shown to suppress growth and extend the lifespan of a broad range of animals. Second, genetic studies have also shown that mice, whose growth hormone function is genetically modified (GM), grow slower and live longer than their wild-type siblings.
Proceedings of the National Academy of Sciences of the United States of America
Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective.
Clinically used anesthetics show amnestic, sedative, hypnotic and immobilizing properties. On a molecular level these drugs affect several receptors in the cell membrane of neurons. By using genetically engineered mice a linkage can now be made between actions on certain receptors and clinically desired and undesired effects. Experiments show that a certain GABA(A) receptor subtype mediates hypnosis and immobility, whereas another subtype is involved in side-effects like sedation and hypothermia.