[Show abstract][Hide abstract] ABSTRACT: Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS.
Proceedings of the National Academy of Sciences 10/2014; 111(42). DOI:10.1073/pnas.1411199111 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 μg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.
[Show abstract][Hide abstract] ABSTRACT: In systems biological studies, precise expression profiling of functionally important gene sets is crucial. Real-time polymerase chain reaction is generally used for this purpose. Despite its widespread acceptance, however, this method is not suitable for multiplex analysis, resulting in an inefficient assay process. One alternative technology in the spotlight is multiplex ligation-dependent probe amplification (MLPA). But MLPA depends on length-based discrimination of amplified products, which complicates probe design and compromises analysis results. Here, we devised a variation of MLPA that utilizes conformation-sensitive capillary electrophoresis, and demonstrated the simplicity of the probe-design process and improved precision of the assay in analyses of 33 Escherichia coli metabolic genes and 16 Caenorhabditis elegans longevity-related genes. The results showed that relative expression could be quantitatively measured over a relevant dynamic range using similar-sized probes. Importantly, the improved precision compared to conventional MLPA promises a wider application of this method for various biological systems.
[Show abstract][Hide abstract] ABSTRACT: Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiological processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: InGaN/GaN green multiple quantum well (MQW) nanopillar light emitting diodes (LEDs), ∼150 nm in diameter and 700 nm in height, were fabricated by inductively coupled plasma etching using a Ni self-assembled nano-size mask. 2.5- and 7-fold improvement in the photoluminescence intensity was recorded for the 515 and 543 nm green LED sample, respectively. Since the size and the shape of both samples were similar, it is believed that the higher In content LEDs would produce more strain relaxation through the fabrication of a nanopillar.
[Show abstract][Hide abstract] ABSTRACT: The manner in which the nervous system regulates animal behaviors in natural environments is a fundamental issue in biology. To address this question, C. elegans has been widely used as a model animal for the analysis of various animal behaviors. Previous behavioral assays have been limited to two-dimensional (2-D) environments, confining the worm motion to a planar substrate that does not reflect three-dimensional (3-D) natural environments such as rotting fruits or soil. Here, we develop a 3-D worm tracker (3DWT) for freely moving C. elegans in 3-D environments, based on a stereoscopic configuration. The 3DWT provides us with a quantitative trajectory, including the position and movement direction of the worm in 3-D. The 3DWT is also capable of recording and visualizing postures of the moving worm in 3-D, which are more complex than those in 2-D. Our 3DWT affords new opportunities for understanding the nervous system function that regulates animal behaviors in natural 3-D environments.
PLoS ONE 02/2013; 8(2):e57484. DOI:10.1371/journal.pone.0057484 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In long-lived C. elegans insulin/IGF-1 pathway mutants, the life-extending FOXO transcription factor DAF-16 is present throughout the animal, but we find that its activity in a single tissue can delay the aging of other tissues and extend the animal's life span. To better understand the topography of DAF-16 action among the tissues, we analyzed a collection of DAF-16-regulated genes. DAF-16 regulated most of these genes in a cell-autonomous fashion, often using tissue-specific GATA factors to direct their expression to specific tissues. DAF-16 could also act cell nonautonomously to influence gene expression. DAF-16 affected gene expression in other cells, at least in part, via the lipid-gene regulator MDT-15. DAF-16, and probably MDT-15, could act cell nonautonomously in the endoderm to ameliorate the paralysis caused by expressing Alzheimer's Aβ protein in muscles. These findings suggest that MDT-15-dependent intercellular signals, possibly lipid signals, can help to coordinate tissue physiology, enhance proteostasis, and extend life in response to DAF-16/FOXO activity.
[Show abstract][Hide abstract] ABSTRACT: The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.
[Show abstract][Hide abstract] ABSTRACT: Mitochondria are essential for various biological processes including cellular energy production. The oxidative stress theory of aging proposes that mitochondria play key roles in aging by generating reactive oxygen species (ROS), which indiscriminately damage macromolecules and lead to an age-dependent decline in biological function. However, recent studies show that increased levels of ROS or inhibition of mitochondrial function can actually delay aging and increase lifespan. The aim of this review is to summarize recent findings regarding the role of mitochondria in organismal aging processes. We will discuss how mitochondria contribute to evolutionarily conserved longevity pathways, including mild inhibition of respiration, dietary restriction, and target of rapamycin (TOR) signaling.
Current Genomics 11/2012; 13(7):519-32. DOI:10.2174/138920212803251427 · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many environmental factors that dynamically change in nature influence various aspects of animal physiology. Animals are equipped with sensory neuronal systems that help them properly sense and respond to environmental factors. Several studies have shown that chemosensory and thermosensory neurons affect the lifespan of invertebrate model animals, including Caenorhabditis elegans and Drosophila melanogaster. Although the mechanisms by which these sensory systems modulate lifespan are incompletely understood, hormonal signaling pathways have been implicated in sensory system-mediated lifespan regulation. In this review, we describe findings regarding how sensory nervous system components elicit physiological changes to regulate lifespan in invertebrate models, and discuss their implications in mammalian aging.
Frontiers in Genetics 10/2012; 3:218. DOI:10.3389/fgene.2012.00218
[Show abstract][Hide abstract] ABSTRACT: NADH-quinone oxidoreductase 1 (NQO1) modulates cellular NAD(+)/NADH ratio which has been associated with the aging and anti-aging mechanisms of calorie restriction (CR). Here, we demonstrate that the facilitation of NQO1 activity by feeding β-lapachone (βL), an exogenous NQO1 co-substrate, prevented age-dependent decline of motor and cognitive function in aged mice. βL-fed mice did not alter their food-intake or locomotor activity but did increase their energy expenditure as measured by oxygen consumption and heat generation. Mitochondrial structure and numbers were disorganized and decreased in the muscles of control diet group but those defects were less severe in βL-fed aged mice. Furthermore, for a subset of genes associated with energy metabolism, mice fed the βL-diet showed similar changes in gene expression to the CR group (fed 70% of the control diet). These results support the potentiation of NQO1 activity by a βL diet and could be an option for preventing age-related decline of muscle and brain functions.
PLoS ONE 10/2012; 7(10):e47122. DOI:10.1371/journal.pone.0047122 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 2.7 times increase in room temperature photoluminescence (PL) intensity and 3.2 times increase in electroluminescence (EL) intensity were observed in blue multi-quantum-well (MQW) GaN/InGaN light emitting diodes (LEDs) as a result of introduction of nano-needle structure embedded with Ag nanoparticles (NPs) into n-GaN film underlying the active MQW region and thick p-GaN contact layer of LEDs. The nano-needle structure was produced by photoelectrochemical etching. Simultaneously a measurable decrease in room temperature decay time from 2.2 ns in control samples to 1.6 ns in PL was observed. The results are explained by strong coupling of recombination in GaN/InGaN MQWs with Ag NPs related localized surface plasmons.
[Show abstract][Hide abstract] ABSTRACT: Optical properties of InGaN/GaN multi-quantum-well (MQW) structures with a nanolayer of Ag/SiO2 nanoparticle (NP) on top were studied. Modeling and optical absorption (OA) measurements prove that the NPs form localized surface plasmons (LSP) structure with a broad OA band peaked near 440-460 nm and the fringe electric field extending down to about 10 nm into the GaN layer. The presence of this NP LSP electrical field increases the photoluminescence (PL) intensity of the MQW structure by about 70% and markedly decreases the time-resolved PL (TRPL) relaxation time due to the strong coupling of MQW emission to the LSP mode.
[Show abstract][Hide abstract] ABSTRACT: Chemical lift-off of (11–22) semipolar GaN using triangular cavities was investigated. The (11–22) semipolar GaN was grown using epitaxial lateral overgrowth by metal-organic chemical vapor deposition on m-plane sapphire, in such a way as to keep N terminated surface of c-plane GaN exposed in the cavities. After regrowing 300 μm thick (11–22) semipolar GaN by hydride vapor phase epitaxy for a free-standing (11–22) semipolar GaN substrate, the triangular cavities of the templates were chemically etched in molten KOH. The (000-2) plane in the triangular cavities can be etched in the  direction with the high lateral etching rate of 196 μm/min. The resulting free-standing (11–22) semipolar GaN substrate was confirmed to be strain-free by the Raman analysis.Highlights► (11–22) semipolar GaN including periodic triangular cavities was grown by MOCVD. ► 300 μm thick (11–22) semipolar GaN was regrown to keep the exposed N-polar GaN. ► The N-polar GaN can be etched to (0002) direction with high etching rate. ► The thick (11–22) semipolar GaN was completely separated from the m-plane sapphire. ► The free-standing (11–22) semipolar GaN without m-sapphire was strain-free.
[Show abstract][Hide abstract] ABSTRACT: We report the fabrication and luminescent characteristics of GaN-based visible light-emitting diode (LED) arrays on Si substrates. For the fabrication of the LEDs, high-quality GaN/ZnO coaxial nanotube heterostructures were prepared by the heteroepitaxial growth of GaN layers on position-controlled ZnO nanotube arrays grown on 1-μm-thick crack-free GaN/Si substrates. The nanostructured LEDs were composed of GaN-based p-n homojunction with GaN/In<sub>1-</sub> x Ga x N multiple quantum wells (MQWs) coaxially coated on GaN/ZnO nanotube heterostructures. The fabricated micro-LEDs emitted visible green light that originated from the MQWs of individual coaxial LEDs. In addition, the origin of the light emission was investigated by measuring cathodoluminescence and electroluminescence spectra.
IEEE Journal of Selected Topics in Quantum Electronics 09/2011; 17(4-17):966 - 970. DOI:10.1109/JSTQE.2010.2062493 · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aging is a fundamental biological process. Characterization of genetic and environmental factors that influence lifespan is a crucial step toward understanding the mechanisms of aging at the organism level. To capture the different effects of genetic and environmental factors on lifespan, appropriate statistical analyses are needed.
We developed an online application for survival analysis (OASIS) that helps conduct various novel statistical tasks involved in analyzing survival data in a user-friendly manner. OASIS provides standard survival analysis results including Kaplan-Meier estimates and mean/median survival time by taking censored survival data. OASIS also provides various statistical tests including comparison of mean survival time, overall survival curve, and survival rate at specific time point. To visualize survival data, OASIS generates survival and log cumulative hazard plots that enable researchers to easily interpret their experimental results. Furthermore, we provide statistical methods that can analyze variances among survival datasets. In addition, users can analyze proportional effects of risk factors on survival.
OASIS provides a platform that is essential to facilitate efficient statistical analyses of survival data in the field of aging research. Web application and a detailed description of algorithms are accessible from http://sbi.postech.ac.kr/oasis.
PLoS ONE 08/2011; 6(8):e23525. DOI:10.1371/journal.pone.0023525 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: GaN-based light-emitting diodes (LEDs) grown on Si(111) substrates were fabricated with a vertical electrode method by using wafer bonding technology. The fabricated vertical LEDs showed a lower operating voltage and larger light output power than conventional LEDs due to enhancement in current spreading and reduction in tensile strain. The light output power of the vertical structured LEDs was 2.6 times higher than that of conventional LEDs, with an operating voltage at 20 mA reduced from 3.5 to 3.2 V.
[Show abstract][Hide abstract] ABSTRACT: A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for the acquisition of a long life span by mutants with reduced respiration in C. elegans. We suggested that increased levels of reactive oxygen species (ROS) produced in the respiration mutants increase HIF-1 activity and lead to this longevity. In this research perspective, we discuss our findings and recent advances regarding the roles of ROS and HIF-1 in aging, focusing on the longevity caused by reduced respiration.
[Show abstract][Hide abstract] ABSTRACT: We report on the electric field dependent carrier dynamics and optical absorption in nonpolar a-plane GaN-based quantum heterostructures grown on r-plane sapphire, which are surprisingly observed to be opposite to those polar ones of the same materials system and similar structure grown on c-plane. Confirmed by their time-resolved photoluminescence measurements and numerical analyses, we show that carrier lifetimes increase with increasing external electric field in nonpolar InGaN/GaN heterostructure epitaxy, whereas exactly the opposite occurs for the polar epitaxy. Moreover, we observe blue-shifting absorption spectra with increasing external electric field as a result of reversed quantum confined Stark effect in these polar structures, while we observe red-shifting absorption spectra with increasing external electric field because of standard quantum confined Stark effect in the nonpolar structures. We explain these opposite behaviors of external electric field dependence with the changing overlap of electron and hole wavefunctions in the context of Fermi's golden rule.
[Show abstract][Hide abstract] ABSTRACT: We investigated the surface plasmon coupling behavior in InGaN/GaN
multiple quantum wells at 460 nm by employing Ag nanostructures on the
top of a roughened p-type GaN. After the growth of a blue light emitting
diode structure, the p-GaN layer was roughened by inductive coupled
plasma etching and the Ag nanostructures were formed on it. This
structure showed a drastic enhancement in photoluminescence and
electroluminescence intensity and the degree of enhancement was found to
depend on the morphology of Ag nanostructures. From the time-resolved
photoluminescence measurement a faster decay rate for the Ag-coated
structure was observed. The calculated Purcell enhancement factor
indicated that the improved luminescence intensity was attributed to the
energy transfer from electron-hole pair recombination in the quantum
well to electron vibrations of surface plasmon at the Ag-coated surface
of the roughened p-GaN.
Proceedings of SPIE - The International Society for Optical Engineering 01/2011; 7945:31-. DOI:10.1117/12.869465 · 0.20 Impact Factor