Eva E R Philipp

Publications of Eva E R Philipp

• Testing the Oxidative Stress Hypothesis of Aging in Primate Fibroblasts: Is There a Correlation Between Species Longevity and Cellular ROS Production?

  Authors: Anna Csiszar, Andrej Podlutsky, Natalia Podlutskaya, William E Sonntag, Steven Z Merlin, Eva E R Philipp, Kristian Doyle, Antonio Davila, Fabio A Recchia, Praveen Ballabh, John T Pinto, Zoltan Ungvari

  The journals of gerontology. Series A, Biological sciences and medical sciences. 01/2012;

  The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts fromThe present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide $$\left({\hbox{ O }}_{2}^{\cdot -}\right)$$ generation, showed an inverse correlation between longevity and steady state or metabolic stress-induced mitochondrial $${\hbox{ O }}_{2}^{\cdot -}$$ production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H(2)O(2)-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.

• Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis.

  Authors: Eva E R Philipp, Lars Kraemer, Frank Melzner, Albert J Poustka, Sebastian Thieme, Ulrike Findeisen, Stefan Schreiber, Philip Rosenstiel

  PloS one. 01/2012; 7(3):e33091.

  The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different speciesThe marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus.

• Physiological responses to self-induced burrowing and metabolic rate depression in the ocean quahog Arctica islandica.

  Authors: Julia Strahl, Thomas Brey, Eva E R Philipp, Gudrun Thorarinsdóttir, Natalie Fischer, Wiebke Wessels, Doris Abele

  The Journal of experimental biology. 12/2011; 214(Pt 24):4223-33.

  Arctica islandica is the longest-lived non-colonial animal found so far, and reaches individual ages of 150 years in the German Bight (GB) and more than 350 years around Iceland (IC). FrequentArctica islandica is the longest-lived non-colonial animal found so far, and reaches individual ages of 150 years in the German Bight (GB) and more than 350 years around Iceland (IC). Frequent burrowing and physiological adjustments to low tissue oxygenation in the burrowed state are proposed to lower mitochondrial reactive oxygen species (ROS) formation. We investigated burrowing patterns and shell water partial pressure of oxygen (P(O(2))) in experiments with live A. islandica. Furthermore, succinate accumulation and antioxidant defences were recorded in tissues of bivalves in the normoxic or metabolically downregulated state, as well as ROS formation in isolated gills exposed to normoxia, hypoxia and hypoxia/reoxygenation. IC bivalves burrowed more frequently and deeper in winter than in summer under in situ conditions, and both IC and GB bivalves remained burrowed for between 1 and 6 days in laboratory experiments. Shell water P(O(2)) was <5 kPa when bivalves were maintained in fully oxygenated seawater, and ventilation increased before animals entered the state of metabolic depression. Succinate did not accumulate upon spontaneous shell closure, although shell water P(O(2)) was 0 kPa for over 24 h. A ROS burst was absent in isolated gills during hypoxia/reoxygenation, and antioxidant enzyme activities were not enhanced in metabolically depressed clams compared with normally respiring clams. Postponing the onset of anaerobiosis in the burrowed state and under hypoxic exposure presumably limits the need for elevated recovery respiration upon surfacing and oxidative stress during reoxygenation.

• Extreme longevity is associated with increased resistance to oxidative stress in Arctica islandica, the longest-living non-colonial animal.

  Authors: Zoltan Ungvari, Iain Ridgway, Eva E R Philipp, Courtney M Campbell, Philip McQuary, Tracy Chow, Miguel Coelho, Elizabeth S Didier, Sara Gelino, Marissa A Holmbeck, Insil Kim, Erik Levy, Danuta Sosnowska, William E Sonntag, Steven N Austad, Anna Csiszar

  The journals of gerontology. Series A, Biological sciences and medical sciences. 04/2011; 66(7):741-50.

  We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. WeWe assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage elimination processes in long-lived A islandica with the shorter-lived hard clam, Mercenaria mercenaria. We compared baseline biochemical profiles, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP). Our data support the premise that extreme longevity in A islandica is associated with an attenuated cellular reactive oxygen species production. The observation of reduced protein carbonyl concentration in A islandica gill tissue compared with M mercenaria suggests that reduced reactive oxygen species production in long-living bivalves is associated with lower levels of accumulated macromolecular damage, suggesting cellular redox homeostasis may determine life span. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level. Following TBHP exposure, we observed not only an association between longevity and resistance to oxidative stress-induced mortality but also marked resistance to oxidative stress-induced cell death in the longer-living bivalves. Contrary to some expectations from the oxidative stress hypothesis, we observed that A islandica exhibited neither greater antioxidant capacities nor specific activities than in M mercenaria nor a more pronounced homeostatic antioxidant response following TBHP exposure. The study also failed to provide support for the exceptional longevity of A islandica being associated with enhanced protein recycling. Our findings demonstrate an association between longevity and resistance to oxidative stress-induced cell death in A islandica, consistent with the oxidative stress hypothesis of aging and provide justification for detailed evaluation of pathways involving repair of free radical-mediated macromolecular damage and regulation of apoptosis in the world's longest-living non-colonial animal.

• Comparative gerontology--from mussels to man.

  Authors: Zoltan Ungvari, Eva E R Philipp

  The journals of gerontology. Series A, Biological sciences and medical sciences. 11/2010; 66(3):295-7.

• Genome-wide association analysis in primary sclerosing cholangitis.

  Authors: Tom H Karlsen, Andre Franke, Espen Melum, Arthur Kaser, Johannes Roksund Hov, Tobias Balschun, Benedicte A Lie, Annika Bergquist, Christoph Schramm, Tobias J Weismüller [......] Andreas Teufel, Heiko Runz, Philip Rosenstiel, Adolf Stiehl, Severine Vermeire, Ulrich Beuers, Michael Manns, Erik Schrumpf, Kirsten Muri Boberg, Stefan Schreiber

  Gastroenterology. 11/2009;

  BACKGROUND & AIMS:: We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of genome-wide association analysis of single nucleotide polymorphism (SNP)BACKGROUND & AIMS:: We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of genome-wide association analysis of single nucleotide polymorphism (SNP) markers. METHODS:: A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/the Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). RESULTS:: The strongest associations were detected near HLA-B at chromosome 6p21 (rs3099844 odds ratio [OR] = 4.8; 95% confidence interval [CI] [3.6, 6.5]; P = 2.6x10-26 and rs2844559 OR = 4.7; 95% CI [3.5, 6.4]; P = 4.2x10-26 in the discovery panel). Outside the HLA complex, rs9524260 at chromosome 13q31 showed significant associations in 3 of 4 study panels. Lentiviral silencing of glypican 6 (GPC6), encoded at this locus, led to the upregulation of pro-inflammatory markers in a chlangiocyte cell-line. Of 15 established ulcerative colitis susceptibility loci, significant replication was obtained at chromosomes 2q35 and 3p21 (rs12612347 OR =1.26; 95% CI [1.06, 1.50] and rs3197999 OR=1.22; 95% CI [1.02, 1.47], respectively), with circumstantial evidence supporting the G protein-coupled bile acid receptor 1 ( GPBAR1) and macrophage-stimulating 1 ( MST1), respectively, as the likely disease genes. CONCLUSIONS:: Strong HLA associations and a subset of genes involved in bile homeostasis and other inflammatory conditions constitute key components of the genetic architecture of PSC.

• Masters of Longevity: Lessons from Long-Lived Bivalves - A Mini-Review.

  Authors: Eva E R Philipp, Doris Abele

  Gerontology. 06/2009;

  The individual ages of bivalve molluscs can be inferred from the age rings laid down every year in the shell, especially in species inhabiting areas with seasonal variability in environmental factorsThe individual ages of bivalve molluscs can be inferred from the age rings laid down every year in the shell, especially in species inhabiting areas with seasonal variability in environmental factors such as food supply and temperature. Animals obtained from different environmental settings can therefore be used to investigate how specific environmental factors shape the process of ageing in this animal class. Some bivalves have extraordinary long life spans. Species like the ocean quahog Arctica islandica and the freshwater pearl mussel Margaritifera margaritifera live for over hundreds of years. Few studies so far have attempted to study the process of ageing, either specifically in long-lived bivalves or generally in very long-lived species. This review summarizes the current knowledge of cellular ageing in bivalves with a focus on the antioxidant system, as well as tissue repair and metabolic capacities of extremely long-lived species. We discuss the applicability of these animals as models for different ageing theories. We recommend a focus of future research on the molecular mechanisms potentially involved in supporting longevity in these species, including evolutionary old cellular mechanisms such as autophagy and apoptosis, as well as diverse cellular repair pathways.

• Evolution and function of innate immune receptors--insights from marine invertebrates.

  Authors: Philip Rosenstiel, Eva E R Philipp, Stefan Schreiber, Thomas C G Bosch

  Journal of innate immunity. 01/2009; 1(4):291-300.

  Innate, nonadaptive immune receptors represent phylogenetically ancient first-line sensors of invariant non-self patterns and other cellular danger signals. From lower animal phyla to vertebrates,Innate, nonadaptive immune receptors represent phylogenetically ancient first-line sensors of invariant non-self patterns and other cellular danger signals. From lower animal phyla to vertebrates, most pathogens are immediately detected by various recognition systems and are destroyed by induction of defense effectors like antimicrobial peptides. Toll-like receptors, nucleotide-binding and oligomerization domain-like receptors and scavenger receptor cysteine-rich proteins represent archetypes of the innate immune receptors, which mediate the complex interaction between the host and microbiota at the interface of epithelial barriers. In this review, we will use knowledge gained from marine invertebrates as a paradigm to describe how this constant molecular crosstalk within the holobiont, i.e. the animal with all its associated microorganisms, contributes to epithelial homeostasis, immunological integrity and maintenance of the resident microbial diversity.

• Size- and age-dependent changes in adductor muscle swimming physiology of the scallop Aequipecten opercularis.

  Authors: Eva E R Philipp, Maike Schmidt, Carina Gsottbauer, Alexandra M Sänger, Doris Abele

  The Journal of experimental biology. 09/2008; 211(Pt 15):2492-501.

  The decline of cellular and especially mitochondrial functions with age is, among other causes, held responsible for a decrease in physiological fitness and exercise capacity during lifetime. WeThe decline of cellular and especially mitochondrial functions with age is, among other causes, held responsible for a decrease in physiological fitness and exercise capacity during lifetime. We investigated size- and age-related changes in the physiology of exercising specimens of the short lived swimming scallop Aequipecten opercularis (maximum life span 8 to 10 years) from the Isle of Man, UK. A. opercularis swim mainly to avoid predators, and a decrease in swimming abilities would increase the risk of capture and lower the rates of survival. Bigger (older) individuals were found to have lower mitochondrial volume density and aerobic capacities (citrate synthase activity and adenylates) as well as less anaerobic capacity deduced from the amount of glycogen stored in muscle tissue. Changes in redox potential, tissue pH and the loss of glutathione in the swimming muscle during the exercise were more pronounced in young compared to older individuals. This indicates that older individuals can more effectively stabilize cellular homeostasis during repeated exercise than younger animals but with a possible fitness cost as the change in physiology with age and size might result in a changed escape response behaviour towards predators.

• Imperceptible senescence: ageing in the ocean quahog Arctica islandica.

  Authors: Doris Abele, Julia Strahl, Thomas Brey, Eva E R Philipp

  Free radical research. 05/2008; 42(5):474-80.

  The ocean quahog Arctica islandica is the longest-lived of all bivalve and molluscan species on earth. Animals close to 400 years are common and reported maximum live span around Iceland is close toThe ocean quahog Arctica islandica is the longest-lived of all bivalve and molluscan species on earth. Animals close to 400 years are common and reported maximum live span around Iceland is close to 400 years. High and stable antioxidant capacities are a possible strategy to slow senescence and extend lifespan and this study has investigated several antioxidant parameters and a mitochondrial marker enzyme in a lifetime range spanning from 4-200 years in the Iceland quahog. In gill and mantle tissues of 4-192 year old A. islandica, catalase, citrate synthase activity and glutathione concentration declined rapidly within the first 25 years, covering the transitional phase of rapid somatic growth and sexual maturation to the outgrown mature stages (approximately 32 years). Thereafter all three parameters kept rather stable levels for > 150 years. In contrast, superoxide dismutase activities maintained high levels throughout life time. These findings support the 'Free Radical-Rate of Living theory', antioxidant capacities of A. islandica are extraordinarily high and thus may explain the species long life span.