International Caenorhabditis elegans Experiment First Flight-Aging (ICE-First-Aging) - 07.14.16
International Caenorhabditis elegans Experiment - First - Aging (ICE-First-Aging) performs an analysis of the aging related protein aggregation and the effects of aging in muscle cells. C. elegans (nematode worms) are relatively simple organisms that are used as a model for a wide variety of biological processes. The ICE-First investigation is a collaborative effort conducted by scientists from several countries which have the opportunity to work as a team to design related experiments that would produce valuable results for scientists across multiple disciplines. Science Results for Everyone
This investigation is one of several on the effects of space flight on the nematode worm Caenorhabditis elegans. Researchers from several countries and disciplines together analyze age-related proteins and aging in muscle cells. Loss of protein balance in muscle cells is recognized as a factor in ageing diseases and may even be a cause of aging. The findings suggest slower protein accumulation and clumping in space-flown nematodes, supporting a link between aging and protein homeostasis. This work gives scientists insight into how space affects organisms at the genetic level, useful for protecting space travelers and the aging on Earth. Experiment Details
Noriaki Ishioka, Japan Aerospace and Exploration Agency, Tsukuba City, Japan
Hiroaki Kagawa, Japan Aerospace and Exploration Agency, Tsukuba, Japan
Atsushi Higashitani, Ph.D., Tohoku University, Miyagi, Japan
Shuji Honda, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Atsushi Higashibata, JAXA, Japan
Nathaniel J. Szewczyk, Ph.D., University of Pittsburg, Pittsburgh, PA, United States
Sponsoring Space Agency
Japan Aerospace Exploration Agency (JAXA)
Japan Aerospace Exploration Agency
ISS Expedition Duration
October 2003 - April 2004
The precursor to ICE-First (flown during Expedition 8), BRIC-60/C. elegans, flew on STS-107 (Columbia). Following the break-up of Columbia upon re-entry into the Earth's atmosphere, the samples were located among debris in East Texas and returned to NASA.
- The ICE-First-Aging experiment examines the effects of microgravity on protein-folding homeostasis (maintenance of internal equilibrium in a cell or organism) in muscle cells.
- This investigation provides a unique opportunity for scientists from several countries to work as a team to design experiments that would produce valuable results for scientists across several various disciplines.
ICE-First-Aging is one of several experiments that investigates the effects of space flight on a model organism in the nematode worm family (Caenorhabditis elegans) and aims to develop links to human physiology in space. The organism chosen for this study is known to be able to mate, reproduce and develop apparently normally during space flight.
C. elegans is a round worm or nematode (Phylum Nematoda) measuring around 1mm and is found naturally in soil. Its body is composed of 959 cells and includes complete reproductive, nervous, muscular, and digestive systems. C. elegans are hermaphrodites (displaying two genders and possessing the ability of self fertilization). Its life span is about 2-3 weeks; although, concerning the liquid medium used for this study at 25°, the life cycle is around 5 days. The entire genome has been sequenced and consists of 97 million base pairs (compared to the 3,000 million found in the human genome) and around 20,000 genes (compared to the 30,000 that humans have) and an entire library of well characterized mutants are available. C. elegans has been used as a model system for various medical pathologies and was the subject of the 2002 Nobel Prize in Medicine or Physiology because the process of programmed cell death or apoptosis was first discovered while studying C. elegans development.
Loss of protein homeostasis is increasingly becoming recognized as an important contributor to several age-associated diseases and may play a causal role in aging. The folding and maintenance of proteins in their native conformation is essential to cellular function. A link between aging and protein homeostasis in the nematode C. elegans is supported by an analysis of the aggregation of polyglutamine (polyQ - a chain of secondary and primary organic compounds) in body wall muscle cells, using transgenic C. elegans expressing polyQ-YFP (yellow fluorescent protein) and also daf-2 (abnormal DAuer Formation-a class of genes in C. elegans that encodes an enzyme that is the insulin growth factor receptor gene) lifespan-extension mutant. DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, adult longevity, reproduction, fat storage, and response to exogenous stressors such as high temperature or bacterial infection. Scientists also analyze sarcomere orientation in the muscle of transgenic C. elegans expressing GFP (green fluorescent protein) in body wall muscle cells.
The possibilities for longer-term space flights are increasing. These types of experiments give scientists an insight into the effect that the environment of space will have on organisms at the genetic level.
By understanding fundamental processes in C. elegans, scientists can better understand the human counterparts. This study can lead to a further understanding of the implications of altered protein homeostasis in aging.
Operational Requirements and Protocols
ICE-First-Aging samples are placed in either the Kubik Topaz or Kubik Amber incubator before and after the launch. Filming is required immediately upon the arrival on Earth for later evaluation. The samples are required to stay either frozen or refrigerated until their return to scientists in Toulouse, France two days prior to landing.
The C. elegans samples are transported to the launch pad in Baikonur, transferred into the Kubik Topaz (incubator with microgravity plate) and kept at 18 degrees C. Three days after the launch, 3 samples are transferred into the Kubik Amber (incubator with centrifuge), while the other five samples remain in Kubik Topaz. On the last flight day, four of the C. elegans samples are injected with a fixative by the crew and all of the samples are placed in Kubik Topaz on the Soyuz and returned to Earth. Upon return to Earth, the containers are filmed to evaluate the behavior of the C. elegans following space flight. The small bags containing the culture of the worms are either frozen or refrigerated until they are returned to their respective principal investigators for detailed analysis.
Decadal Survey Recommendations
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Checkpoint-induced apoptosis is involved in maintaining genomic stability through the elimination of cells that have failed to repair DNA damage. However, the occurrence of checkpoint-induced and other types of physiological apoptosis in animals during or as a result of space flight has not been documented. Approximately 300 germ cells of C. elegans undergo apoptosis (programmed cell death) during normal development. DNA damage-induced checkpoint apoptosis also occurs in germ cells, at the meiotic pachytene nucleus stage (stage of chromosomal crossover). Results indicate that pachytene checkpoint apoptosis and physiological apoptosis in germ cells occurred normally in the space exposed nematodes. Thus, the normal occurrence of several kinds of apoptosis, including checkpoint apoptosis, during space flight supports the hypothesis that humans would retain the ability to eliminate cells that have failed to repair DNA lesions introduced by cosmic radiation during spaceflight (Higashitani 2005).^ back to top
Higashibata A, Higashitani A, Adachi R, Kagawa H, Honda S, Honda Y, Higashitani N, Sasagawa-Saito Y, Miyazawa Y, Szewczyk NJ, Conley CA, Fujimoto N, Fukui K, Shimazu T, Kuriyama K, Ishioka N. Biochemical and Molecular Biological Analyses of space-flown nematodes in Japan, the First International Caenorhabditis elegans Experiment (ICE-First). Microgravity Science and Technology. 2007; 19(5-6): 159-163. PMID: 19513185.
Honda Y, Higashibata A, Matsunaga Y, Yonezawa Y, Kawano T, Higashitani A, Kuriyama K, Shimazu T, Tanaka M, Szewczyk NJ, Ishioka N, Honda S. Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans. Scientific Reports. 2012 July 5; 1(487): 7 pp. DOI: 10.1038/srep00487. PMID: PMID: 22768380.
Szewczyk NJ, Tillman J, Conley CA, Granger L, Segalat L, Higashibata A, Honda S, Honda Y, Kagawa H, Adachi R, Higashitani A, Fujimoto N, Kuriyama K, Ishioka N, Fukui K, Baillie D, Rose A, Gasset G, Eche B, Chaput D, Viso M. Description of International Caenorhabditis elegans Experiment first flight (ICE-First). Advances in Space Research. 2008; 42(6): 1072 -1079. DOI: 10.1016/j.asr.2008.03.017.
Honda Y, Honda S, Narici M, Szewczyk NJ. Spaceflight and Ageing: Reflecting on Caenorhabditis elegans in Space. Gerontology. 2014; 60(2): 138-142. DOI: 10.1159/000354772. PMID: 24217152.
Ground Based Results Publications
Zhao Y, Johnsen RC, Baillie D, Rose A. Worms in Space? A Model Biological Dosimeter. Gravitational and Space Biology. 2005; 18(2): 11-16.
This image shows a magnified image of 2 adult worms and 1 juvenile worm crawling in the liquid media that was used for the ICE-First mission.
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Photo of a vented experiment container (EC) along with culture bags containing C. elegans. The culture bags are housed inside of vented ECs.
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Photo of Kubik Amber and Kubik Topaz incubators ready for flight.
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