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.Principal Investigator(s)
Japan Aerospace Exploration Agency (JAXA)Sponsoring Organization
Information PendingISS Expedition Duration
October 2003 - April 2004
8Previous ISS Missions
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.
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.Earth Applications
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.
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.Operational Protocols
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.
ICE-First-Aging performs an analysis of the aging related protein aggregation and the effects of aging in muscle cells of C. elegans worms during ISS Expedition 8.
To examine the effect of space flight on muscle protein aggregation, space-exposed and ground control nematodes were compared during the larval and young adult stages from the ICE-First investigation. The polyglutamine (portion of protein) aggregation in the space-flown organisms was less than that in the ground control ones. These findings suggest that the protein aggregation rate of the space-flown nematodes was slower than that of the ground controls (Higashibata 2007).
Szewczyk 2008, indicated that the total stowage space required for the eight type I cassettes to house the ICE-First investigation was minimal. Despite this limited size, mass experiments for investigators from four space agencies were returned, a total of 53 independent samples, each of which contained more than 100 individual animals. The concept of accommodating a number of experiments within a limited available volume and upmass appears to have merit.
By setting flight constraints first and bringing together established C. elegans researchers second, it was possible to design and successfully execute the flight portion of these experiments within one year. In the past, the time from flight grant solicitation to completion of a flight experiment has been longer than 3 years (Szewczyk 2008).
Adachi R, Higashitani A, Kuriyama K, Higashibata A, Honda S, Honda Y, Shimazu T, Kagawa H, Higashitani N, Sasagawa Y, Ishioka N, Miyazawa Y, Szewczyk NJ, Fukui K, Conley CA, Fujimoto 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. PMID: 19513185.
Adachi R, Tillman J, Higashitani A, Kuriyama K, Granger L, Higashibata A, Segalat L, Honda S, Gasset G, Honda Y, Kagawa H, Baillie D, Ishioka N, Fukui K, Szewczyk NJ, Conley CA, Fujimoto N, Rose A, 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.
Rose A, Zhao Y, Hohnsen R, Baillie D. Worms in Space? A Model Biological Dosimeter. Gravitational & Space Biology; 2005.