The fruit of Terminalia chebula Retz has been used as a traditional medicine in Asia and contains tannic acid, chebulagic acid, chebulinic acid and corilagin. Extract from T. chebula seeds (TCE) has various biological functions. We observed the neuroprotective effects of TCE against ischemic damage in the hippocampal C1 region (CA1) of the gerbil that had received oral administrations of TCE (100 mg/kg) once a day for 7 days before the induction of transient cerebral ischemia.
Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders: Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases
INTRODUCTION: The aim of this study was to determine the effect of hNT neuron transplants on motor neuron function in SOD1 (G93A) mice when motor deficits were already apparent. METHOD: The hNT neurons were implanted into L(4)-L(5) segments of the ventral horn spinal cord of mice at 15-16 weeks of age: either G93A mice, transgenic mice carrying the normal allele for human SOD1 gene (hTg), or control wild type mice (wt). Behavioral tests (rotorod, beam balance, extension reflex, footprint) were performed prior to transplantation and at weekly intervals afterwards.
The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.
SIRT1 is the mammalian homologue of yeast silent information regulator (Sir)-2, a member of the sirtuin family of protein deacetylases which have gained much attention as mediators of lifespan extension in several model organisms. Induction of SIRT1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's disease. SIRT1 induction, either by sirtuin activators such as resveratrol, or metabolic conditioning associated with caloric restriction (CR), could be neuroprotective in several ways.
The nicotinamide adenine dinucleotide (NAD)-activated protein deacetylase Sir2p/Sirt1 has been strongly implicated in the modulation of replicative lifespan and promotion of longevity. Part of Sirt1's capacity for lifespan extension in complex organisms may be attributed to its protective activity against neuronal degeneration. Manipulation of Sirt1's activity or levels by pharmacological and genetic means in several models of neurodegenerative diseases demonstrated its neuroprotective credentials.
This article proposes that behavioural advancement during mammalian evolution had been in part mediated through extension of total developmental time. Such time extensions would have resulted in increased numbers of neuronal precursor cells, hence larger brains and a disproportionate increase in the neocortex. Larger neocortical areas enabled new connections to be formed during development and hence expansion of existing behavioural circuits.
Sir2 ? Sirt1 and its orthologues are known lifespan extension factors in several aging models from yeast to invertebrates. Sirt1 activation is also known to be beneficial and protective in both invertebrate and mammalian models of neurodegenerative disease. Sirt1ís lifespan extension effect, as well as the beneficial outcome of its activation in models of aging-associated diseases, is often attributed to its ability to instill a gene expression profile that is pro-survival and antiaging.
Signaling by target of rapamycin (mTOR in mammals) has been shown to modulate lifespan in several model organisms ranging from yeast to mice. In mice, reduced mTOR signaling by chronic rapamycin treatment leads to life span extension, raising the possibility that rapamycin and its analogs may benefit the aging brain and serve as effective treatments of age-related neurodegenerative diseases. Here, we review mTOR signaling and how neurons utilize mTOR to regulate brain function, including regulation of feeding, synaptic plasticity and memory formation.
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.
Insulin and insulin-like signaling regulate survival and lifespan in a variety of animal species, from nematodes and flies to higher vertebrates and mammals. Recently, it was shown that brain IGF-I receptor and brain IRS2 control mammalian lifespan, and that this occurs through neuroendocrine mechanisms, control of energy metabolism and modified stress resistance. Furthermore, it was demonstrated that insulin receptor substrate molecules are implicated downstream of insulin and IGF receptors in the extension of lifespan.