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Abstract

Invertebrate model organisms represent an invaluable tool for the biology of aging research. They possess a number of advantages over vertebrate models in aging studies, including short lifespan, small size (a key advantage for large-scale lifespan investigations), ease of propagation, transparent bodies, and powerful genetics. These organisms also present advantages as simplified animal models enabling the study of individual processes. Studies using invertebrate models to investigate the biology of aging have primarily used the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. In this chapter, we the relative benefits and challenges in using these models as well as the tools these organisms contribute to aging research. Finally, a number of other invertebrate models have been developed, each with its own key advantages. These other invertebrate models are described in the third part of this chapter along with research done in these systems in the biology of aging.

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Aging is a multi-factorial process, however, it is generally accepted that reactive oxygen species (ROS) are significant contributors. Mitochondria are important players in the aging process because they produce most of the cellular ROS. Despite the strength of the free-radical hypothesis, the use of free radical scavengers to delay aging has generated mixed results in vertebrate models, and clinical evidence of efficacy is lacking. This is in part due to the production of pro-oxidant metabolites by many antioxidants while scavenging ROS, which counteract their potentially beneficial effects. As such, a more effective approach is to enhance mitochondrial metabolism by reducing electron leakage with attendant reduction of ROS generation. Here, we report on the actions of a novel endogenous indole derivative, indolepropionamide (IPAM), which is similar in structure to melatonin. Our results suggest that IPAM binds to the rate-limiting component of oxidative phosphorylation in complex I of the respiratory chain and acts as a stabilizer of energy metabolism, thereby reducing ROS production. IPAM reversed the age-dependent decline of mitochondrial energetic capacity and increased rotifer lifespan, and it may, in fact, constitute a novel endogenous anti-aging substance of physiological importance.
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In most animals, aging is an irreversible process; however the species Turritopsis sp. has been observed to undergo a rejuvenation process as many as 14 times. In the present study, we used multiplexed RNA libraries to obtain the transcriptome from four developmental stages (St) of Turritopsis sp., including (I) immature medusa, (II) dumpling, (III) dumpling with a short stolon, and (IV) polyp, which had recently rejuvenated. A total of 4.02 billion paired-end reads were assembled de novo, yielding 90,327 contigs. Our analyses revealed that significant blast hits were recovered for 74% of the assembled contigs, and 19% were successfully annotated with gene ontology (GO) terms. A BLAST search demonstrated that 32% of the contigs were most similar to Hydra vulgarissequences. Raw reads from each sample were mapped against the contigs to find St-specific genes. This represents the first comprehensive set of de novo transcriptome data for this species, which may provide clues toward a better understanding of cyclical rejuvenation in multicellular animals.
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Dietary restriction (DR) increases life span in many types of animals. The response to chronic DR may be an adaptation to environments with variable food levels. This study uses the comparative method to test evolutionary predictions about the origin of the response to DR, using data from 10 species of rotifers. Most species, but not all, responded to DR by increasing mean life span, maximum life span, reproductive life span, mortality rate doubling time, and initial mortality rate. Interspecific comparisons did not show the predicted correlations between the strength of the response to DR and either reproductive life span, age of first reproduction, or total reproduction. There was support for the idea that the response to chronic DR is associated with changes in reproductive allocation during short-term periods of starvation: species that reduced reproduction when starved increased their life spans under DR, whereas species that continued to reproduce when starved decreased their life spans under DR.
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A significant proportion of mammalian genes are not represented in the genomes of Drosophila, Caenorhabditis or Saccharomyces, and many of these are assumed to have been vertebrate innovations. To test this assumption, we conducted a preliminary EST project on the anthozoan cnidarian, Acropora millepora, a basal metazoan. More than 10% of the Acropora ESTs with strong metazoan matches to the databases had clear human homologs but were not represented in the Drosophila or Caenorhabditis genomes; this category includes a surprising diversity of transcription factors and metabolic proteins that were previously assumed to be restricted to vertebrates. Consistent with higher rates of divergence in the model invertebrates, three-way comparisons show that most Acropora ESTs match human sequences much more strongly than they do any Drosophila or Caenorhabditis sequence. Gene loss has thus been much more extensive in the model invertebrate lineages than previously assumed and, as a consequence, some genes formerly thought to be vertebrate inventions must have been present in the common metazoan ancestor. The complexity of the Acropora genome is paradoxical, given that this organism contains apparently few tissue types and the simplest extant nervous system consisting of a morphologically homogeneous nerve net.
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In our previous studies of the Hydra nerve ring, we proposed the following hypothesis: “The nerve ring in the hypostome of Hydra is a central nervous system (CNS)-like neuronal structure.” Related to this hypothesis, we have started to survey the nerve ring immunocytochemically using antibodies against neuropeptides throughout the whole phylum of cnidarians. In the present study, we describe nerve rings in hydrozoan medusae. We examined the medusae of five hydrozoan species belonging to three orders: Eirene sp. (order Leptomedusae), Craspedacusta sowerbyi (order Limnomedusae), Sarsia tubulosa, Turritopsis nutricula, and Cladonema radiatum (order Anthomedusae). We observed a well-developed nerve ring in all species. The nerve ring runs circumferentially around the margin of the bell. In all cases, the nerve ring was visualized by plural antibodies, suggesting that it contains different neural subpopulations. In C. radiatum, antibodies against four different neuropeptides labeled the nerve ring. We established clear (without undesirable cross-reactions) double-staining procedures with two rabbit primary antibodies. Using the double-staining method, three neural subsets visualized by three antibodies revealed completely separate neural populations. The results show that the nerve ring is a common feature in hydrozoan medusae and has a complex heterogeneous structure composed of different neural subsets
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Evidence from animal studies and human famines suggests that starvation may affect the health of the progeny of famished individuals. However, it is not clear whether starvation affects only immediate offspring or has lasting effects; it is also unclear how such epigenetic information is inherited. Small RNA-induced gene silencing can persist over several generations via transgenerationally inherited small RNA molecules in C. elegans, but all known transgenerational silencing responses are directed against foreign DNA introduced into the organism. We found that starvation-induced developmental arrest, a natural and drastic environmental change, leads to the generation of small RNAs that are inherited through at least three consecutive generations. These small, endogenous, transgenerationally transmitted RNAs target genes with roles in nutrition. We defined genes that are essential for this multigenerational effect. Moreover, we show that the F3 offspring of starved animals show an increased lifespan, corroborating the notion of a transgenerational memory of past conditions.
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Study of negligibly senescent animals may provide clues that lead to better understanding of the cardiac aging process. To elucidate mechanisms of successful cardiac aging, we investigated age-related changes in proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in the heart of the ocean quahog Arctica islandica, the longest-lived noncolonial animal (maximum life span potential: 508 years). We found that in the heart of A. islandica the level of oxidatively damaged proteins did not change significantly up to 120 years of age. No significant aging-induced changes were observed in caspase-like and trypsin-like proteasome activity. Chymotrypsin-like proteasome activity showed a significant early-life decline, then it remained stable for up to 182 years. No significant relationship was observed between the extent of protein ubiquitination and age. In the heart of A. islandica, an early-life decline in expression of HSP90 and five mitochondrial electron transport chain complexes was observed. We found significant age-related increases in the expression of three cytokine-like mediators (interleukin-6, interleukin-1β, and tumor necrosis factor-α) in the heart of A. islandica. Collectively, in extremely long-lived molluscs, maintenance of protein homeostasis likely contributes to the preservation of cardiac function. Our data also support the concept that low-grade chronic inflammation in the cardiovascular system is a universal feature of the aging process, which is also manifest in invertebrates.
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Anatomical studies show that three families, Verticordiidae, Poromyidae and Cuspidariidae, have many features in common. All are carnivores, have similar digestive systems, and have a horizontal septum dividing the mantle into infra- and supraseptal cavities. This partition is developed to different degrees in the different families. In the Verticordiidae the reduced gill is connected by a membrane to the body mantle and intersiphonal septum. The species rely mainly on ciliary currents for respiration and water change. In the Cuspidariidae, there is a thick, muscular sheet which in the most specialized species is pierced by only four pairs of pores. Regular pumping movements change the water in the mantle cavities. Because of their obvious relation, the three families are combined within the suborder Septibranchia, of the order Anomalodesmata (Bivalvia). On the basis of this study the Verticordiidae and Poromyidae are more closely related to one another than either is to the Cuspidariidae. This is demonstrated by the differences in the siphon structure and reproductive systems. The first two families are hermaphrodite, short-siphoned, have a large forward projecting valve at the base of the inhalant siphon, and bear 13 or 15 short tapering tentacles around the siphonal apertures. The Cuspidariidae are dioecious, long-siphoned, the inhalant aperture being sealed internally by a simple vertical sheet pierced by a keyhole slit, and consistently have three dorsal exhalant tentacles and four ventral inhalant tentacles. In the past, the taxonomy of the family Cuspidariidae has been based solely on hinge characteristics. This study, on the basis of gross morphological differences, identifies three genera: Cuspidar, Halonympha and a new genus, Protocuspidaria . Subdivisions of these genera continue to be based on hinge characters, there being few anatomical differences. Protocuspidaria, Halonympha and Cuspidaria form a series in the development of the septum from a reduced eulamellibranch gill to the typical muscular septum of the genus Cuspidaria . This involves a vast increase in musculature with the development of dorsal attachments of these muscles onto the shell. Associated with this development is a decrease in the size of the palps and an increase in the rostral length of the shell. The septum in both the Poromyidae and Cuspidariidae contains five pairs of muscles; the anterior and posterior septal muscles, the inner and outer longitudinal septal muscles and the lateral septal muscles. These muscles lie between two epithelial layers which are continuous with those of the mantle and the viscera. In the Poromyidae, the septum is already very muscular and pierced by two ( Poromya ) or three ( Cetoconcha ) pairs of grouped branchial apertures. In the Cuspidariidae, while there is a progressive increase in the musculature of the septum, the branchial apertures are always set in a single series on either side of the foot. Studies on the comparative morphology of the families, particularly of the nervous systems and musculature, show that the septum is developed mainly from the gill. Except for Cetoconcha , where a few filaments of the outer demibranch persist posteriorly and form the third posterior group of branchial apertures, the openings in the septum are derived from the descending lamella of the inner demibranch. The musculature is mainly derived from that of the inner demibranch. A reduced gill becomes connected via a membrane, laterally to the mantle, anteriorly to the margin of the mouth, posteriorly to the intersiphonal septum and medially to the foot. The anterior septal muscle of the Poromyidae and Cuspidariidae is homologous with the axial muscle of eulamellibranch bivalves. This enlarges, extends forward and, in all but Protocuspidaria , makes an anterior dorsal attachment on the shell. The posterior septal muscle is derived by an increase, fusion and extension of the longitudinal filamentar muscles of several posterior gill filaments of the outer demibranch. This, in all but the more ‘primitive’ genera ( Protocuspidaria and Halonympha ), also makes a posterior dorsal attachment. The increase and modification of the longitudinal filamentar muscles of the inner demibranch gives rise to the bulk of the septum, forming the lateral septal muscles and the pore-closing mechanism. Pallial muscle along the lateral margin of the septum probably gives rise to the outer longitudinal septal muscle. There is also firm evidence that the inner longitudinal muscle, which provides the seal around the foot, is pedally derived. The Verticordiidae, Poromyidae and Cuspidariidae have a specialized carnivorous habit. In the Verticordiidae food capture is by trapping of passing prey on sticky tentacles, while in the Cuspidariidae feeding involves active use of the muscular pumping septum to suck in the prey detected by the sensory tentacles. In the Poromyidae, however, the seal is incomplete posterior to the foot, and the pumping mechanism is possibly not as efficient as it is in the Cuspidariidae, but neither are the tentacles sticky as they are in the Verticordiidae. It therefore seems likely that they utilize a pumping action that is supplemented by ciliary action for both respiration and drawing in food.
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As a subject attracting interest because of economic applications, egg-laying has been studied in the house fly and in other insects with a view to determining the factors affecting the total number of ova deposited. Because of its possible bearing on a question which was formerly under investigation by the author, an examination of the rate of egg production in the fruit fly Drosophila melanogaster was under taken for the determination of individual variations, and the similari ties, if any, among different mutants. It is not intended in this account to go into the possible experimental modification of oviposition rate nor to add anything to a treatment of the external influences affecting oviposition in insects in general (Richardson, 1925) but rather to describe the process as found under what may be called “¿�normal” conditions for the life of this genus. Not only because of easy cultiva tion in the laboratory, eliminating special vivaria as may be required for other insects, but also due to the variety of effective media available (Pearl, 1926; Bridges, 1932) and the small amount of space necessary, Drosophila is a form very suitable for the study of egg-laying. Of greater moment is the fact that Drosophila lays eggs regularly over a longer period and in larger numbers as compared with the activity of certain other forms in these respects; the Cecropia moth, for example, requires only three or four days to lay its quota of several hundred eggs (Rau, 1910). An interesting and compact account of the biology of the pomace fly and complete references up to 1925 are contained in the monograph of Morgan, Bridges, and Sturtevant (1925); for this reason only a few experiments bearing on this study need be cited. Castle and associates (1906) demonstrated that close inbreeding did not diminish the fertility of Drosophila, provided fertile pairs were selected to continue the stock. For a detailed account of the mor phology of the ovary and the internal phenomena of reproduction, reference may be made to the description of Nonidez (1920), and of Laurinat (1931), while the courtship and other external phenomena of reproduction have been observed by Sturtevant (1915, 1921). That factors for egg size exist in all four linkage groups has been brought
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In this paper is described the composition and method of making a standard synthetic medium for the laboratory cultivation of Drosophila melanogaster. It is shown that this medium is greatly superior to the banana medium commonly used for this purpose in respect of both the fertility and the mortality of flies kept on it. The range of superiority in respect of fertility is at different densities of population from about 48 per cent at the lowest, to 98 per cent at the highest densities experimentally reported here. The general experience of the laboratory with this medium, which frees experimental work on Drosophila from the incubus of the highly variable banana, shows it to have other points of superiority besides those discussed here.
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Sea urchins have a different life history from humans and traditional model organisms used to study the process of aging. Sea urchins grow indeterminately, reproduce throughout their life span and some species have been shown to exhibit negligible senescence with no increase in mortality rate at advanced ages. Despite these properties, different species of sea urchins are reported to have very different natural life spans providing a unique model to investigate cellular mechanisms underlying life span determination and negligible senescence. To gain insight into the biological changes that accompany aging in these animals, proteomic profiles were examined in coelomic fluid from young and old sea urchins of three species with different life spans: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate life span. The proteomic profiles of cell-free coelomic fluid were complex with many proteins exhibiting different forms and extensive post-translational modifications. Approximately 20% of the protein spots on 2-D gels showed more than two-fold change with age in each of the species. Changes that are consistent with age in all three species may prove to be useful biomarkers for age-determination for these commercially fished marine invertebrates and also may provide clues to mechanisms of negligible senescence. Among the proteins that change with age, the ectodomain of low-density lipoprotein receptor-related protein 4 (LRP4) was significantly increased in the coelomic fluid of all three sea urchin species suggesting that the Wnt signaling pathway should be further investigated for its role in negligible senescence.
Article
Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures.
Article
We used the monogonont rotifer, Brachionus calyciflorus, to study the effect of ambient temperatures of 16°C, 22°C, and 29°C on longevity and life history parameters. We found that temperature had a significant relationship with longevity. At lower temperature, there was prolongation of the pre-reproductive and reproductive periods, but fecundity was reduced significantly due to suppression of the reproductive rate. When lifespan of short- and long-lived rotifers was compared, we found that the significant longevity difference in these rotifers was due to extension of reproductive and post-reproductive periods. The fecundity was significantly higher in longer lived rotifers due to the extension of the reproductive period, but the reproductive rate was significantly lower in these rotifers. A consistent negative relationship between rotifer longevity and the rate of reproduction was observed at all temperatures, and it was particularly pronounced in rotifers reproducing heavily at the end of the reproductive stage of their life cycle. The combined rate of living/oxidative damage theory may help explain the temperature effects that we observed.
Article
COSTS of reproduction occur when an increase in reproductive rate reduces future reproduction by increasing mortality or reducing fertility. Such costs have been demonstrated in plants and animals in laboratory and field studies1–5. Their importance lies in their possible role in the evolution of life histories and of senescence6–15. An understanding of their mechanisms will also reveal the nature of the physiological constraints on longevity and fertility. Most accounts assume that these occur as a result of competition for nutrient allocation between growth, storage, somatic maintenance and reproduction16–21. An increase in reproductive rate would then result in a denial of nutrients to other processes, resulting in a drop in life expectancy or future fertility. Some support for this point of view comes from the finding that lifespan is lengthened in female Drosophila melanogaster that have inactive or absent ovaries22–23 or that are experimentally induced to produce fewer eggs24. Increased exposure to males, however, also results in a drop in lifespan24–26. We show here that mating with males greatly reduces lifespan in female fruitflies whose rates of egg-production and egg-fertility do not differ, suggesting both that simple nutrient allocation to reproduction is not its only physiological cost, and that males can cause females to remate at a frequency that results in reduced female lifetime reproductive success.
Article
1 Extension of life span by food shortage, often mimicked by calorie restriction (CR) in the laboratory, is one of the most common life-history alterations in eukaryotes. Although the life-history of offspring often changes in response to the parental environment, it has remained ambiguous whether or not CR-induced longevity is transmitted to the next generation. 2 Here, we investigated the effects of CR on life span, oxidative stress resistance and the expression levels of two antioxidant enzymes, catalase and manganese superoxide dismutase (Mn SOD), in the parthenogenetic rotifer Brachionus plicatilis during two consecutive generations. 3 Rotifers under CR lived 50% longer than those fed ad libitum (AL) in association with enhancement of oxidative stress resistance and increased mRNA levels of catalase and Mn SOD. 4 The daughters from the CR-treated mothers lived 20% longer than those from the mothers fed AL regardless of food-rich and CR conditions for the daughter. Furthermore, the daughters from the CR-treated mothers were endowed at birth with a higher ability to resist oxidative stress and the increased mRNA levels for catalase, but not for Mn SOD. In agreement with the mRNA expression patterns, CR increased the protein levels of catalase and Mn SOD in eggs and the whole body of mothers, respectively. 5 Our results for these asexually reproducing rotifers provide the first evidence that the longevity and oxidative stress resistance resulting from CR can be passed on to subsequent generations.
Article
The population densities, spatial distributions, size frequencies, growth rates, longevity and reproductive activities of sub-populations of the sea urchin Lytechinus variegatus were investigated over a two-year period. Sea urchins were examined in three habitats in Saint Joseph Bay, Florida, which is within the northern limits of their distribution. Densities of sea urchins, which ranged as high as 35 individuals ·−2, fluctuated seasonally at all sites and were higher in seagrass beds comprised of Thalassia testudinum than Syringodium filiforme or on a sand flat. A cold front caused large-scale, catastrophic mortality among adult, and especially juvenile, sea urchins in nearshore habitats of the Bay in the spring of 1993, leading to a dramatic decline in sea urchin densities at the Thalassia seagrass site. The population recovered over 6 months at this site and was attributable to immigration of new adults. Juvenile recruitment displayed both interannual and site-specific variability, with recruitment being highest in seagrass habitats in fall and spring. The most pronounced recruitment event occurred in fall 1993 at the Thalassia site. Spatial distributions of adult individuals ascertained monthly never varied from random in the seagrass beds (T. testudinum and S. filiforme) or during spring, summer or fall months on the sand flat. Nonetheless, aggregations of adult sea urchins were observed on the sand flat in the winter months and were associated with patchy distributions of plant food resources. Juvenile sea urchins (< 25 mm test diameter) exhibited aggregations at all sites and 67 % of all juveniles under 10 mm test diameter (91 of 165 individuals observed) were found under the spine canopies of adults. Measurements of the inducibility of spawning indicated peak gametic maturity in all three sub-populations in spring and summer. Gonad indices varied between habitats and years, but distinct maxima were detected, particularly in spring 1993 and late summer 1994. The mean gonad index of individuals at the Syringodium seagrass site was 2- to 4-fold higher than the other sites in spring 1993 and gonad indices were much higher at all sites in spring of 1993 than 1994. Estimates of growth based on changes in size frequency cohorts coupled with measurements of growth bands on lantern demipyramids indicated that L. variegatus in three habitats of Saint Joseph Bay have similar growth rates and attain a mean test diameter of approximately 35 mm in one year. In contrast to populations within the central biogeographical range of the species, which may attain test diameters up to 90 mm, the largest individuals recorded in Saint Joseph Bay were 60 mm in test diameter, and almost all individuals were no more than 45 mm in test diameter or two years of age. The demographics of L. variegatus in the northern limits of their distribution appear to be strongly influenced by latitudinally driven, low-temperature events and secondarily by local abiotic factors, especially springtime low salinities, which may negatively impact larval development and recruitment.
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Rotifers have been used to study the mechanisms of ageing for more than a century, but the underlying molecular basis of ageing in rotifers is largely unknown. The insulin/insulin-like growth factor (IGF-1) signaling pathway has been found to regulate the lifespan of evolutionarily distinct eukaryotes from yeast to mammals. We therefore assume that the insulin/IGF-1 pathway is a candidate for regulating the rotifer’s lifespan. Accordingly, we examined the action of an inhibitor to PI3-kinase involved in the pathway for the rotifer Brachionus plicatilis O. F. Müller. This kinase was first discovered as age-1 to regulate the longevity of Caenorhabditis elegans. As expected, the inhibitor treatment resulted in the extension of lifespan by 30% compared to the reference group without the treatment, whereas reproductive characters were not apparently changed. These results were consistent with those observed in C. elegans, suggesting that the lifespan of B. plicatilis is likely to be regulated by the signaling pathway involving PI3-kinase.
Article
Existing data imply that the cnidarian Hydra vulgaris does not undergo senescence. In contrast, the related species Hydra oligactis shows increased mortality and physiological deterioration following sexual reproduction. Hydra thus offers the chance to study a striking difference in lifespan in members of the same genus. Adult Hydra possess three well-characterized stem cell populations, one of which gives rise to both somatic cells and gametes. The lack of senescence in Hydra vulgaris raises the question of how these stem cell populations are maintained over long periods of time. Investigation of the roles in Hydra of proteins involved in cellular stress responses in other organisms should provide insight into this issue. Proteins of particular interest include the Hsp70 family proteins and the transcription factor FoxO.
Article
The life history of sea urchins is fundamentally different from that of traditional models of aging and therefore they provide the opportunity to gain new insight into this complex process. Sea urchins grow indeterminately, reproduce throughout their life span and some species exhibit negligible senescence. Using a microarray and qRT-PCR, age-related changes in gene expression were examined in three tissues (muscle, esophagus and nerve) of the sea urchin species Strongylocentrotus purpuratus. The results indicate age-related changes in gene expression involving many key cellular functions such as the ubiquitin-proteasome pathway, DNA metabolism, signaling pathways and apoptosis. Although there are tissue-specific differences in the gene expression profiles, there are some characteristics that are shared between tissues providing insight into potential mechanisms that promote lack of senescence in these animals. As an example, there is an increase in expression of genes encoding components of the Notch signaling pathway with age in all three tissues and a decrease in expression of the Wnt1 gene in both muscle and nerve. The interplay between the Notch and Wnt pathways may be one mechanism that ensures continued regeneration of tissues with advancing age contributing to the general lack of age-related decline in these animals.
Article
even-skipped represses wingless and transforms cells that would normally secrete naked cuticle into denticle secreting cells. The GAL4 system can thus be used to study regulatory interactions during embryonic devel- opment. In adults, targeted expression can be used to generate dominant phenotypes for use in genetic screens. We have directed expression of an activated form of the Dras2 protein, resulting in dominant eye and wing defects that can be used in screens to identify other members of the Dras2 signal transduction path- way. SUMMARY
Article
Freshwater planarians have a large totipotent stem cell population allowing high rates of cell renewal and morphological plasticity. It is often suggested that they are able to rejuvenate during fission, regeneration and starvation. These features, together with the rapidly expanding molecular toolset, make planarians such as Schmidtea polychroa and S. mediterranea interesting for ageing research. Yet, the basic demographic and physiological data are lacking or still based on fragmentary observations of one century ago. Here, we present the first longitudinal physiological study of the species S. polychroa. Survival, size and metabolic rate, measured by microcalorimetry, of a cohort of 28 individuals were followed over a period of three years. Sexual maturity was reached during the second month after which the worms continued growing up to 5 months. This initial growth phase was followed by alternating periods of synchronised growth and degrowth. Although mass-specific metabolic rates declined during the initial growth phase, no changes were found later in life. The absence of metabolic ageing may be explained by the very high rate of cell renewal during homeostasis and alternating phases of degrowth and growth during which tissues are renewed. Surprisingly, all deaths occurred in pairs of worms that were housed in the same culture recipient, suggesting that worms did not die from ageing. Taking into account the metabolic and demographic data, we suggest that S. polychroa shows negligible ageing. Detailed analyses of size and metabolic rate revealed a remarkable biphasic allometric scaling relation. During the initial growth phase (months 1-5) the allometric scaling exponent b was 0.86 while later in life, it increased to an unusually large value of 1.17, indicating that mass-specific metabolic rate increases with size in adult S. polychroa.