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RESEARCH SPOTLIGHT Lessons from the sea: Sea urchins as Andrea Bodnar, Ph.D., Science Director, models for aging and research Gloucester Marine Institute

NEB has long recognized the potential of the marine urchin development facilitated Tim Hunt’s Nobel prize great promise for discovering naturally occurring environment as a source for new discovery and winning discovery of cyclins, that play a key cancer prevention mechanisms. the need to protect and preserve the ocean’s vast role in controlling . Part of their value as a Initial studies with sea urchins have demonstrated biodiversity for the benefit of humankind. The unique model organism is their close genetic relationship with that the circulating cells (coelomocytes) are highly adaptations of marine organisms have made them ; as non-chordate deuterostomes, sea urchins resistance to DNA damaging agents, invoke a robust valuable models for biomedical research, provided are one of our closest relatives. This makes DNA repair response and can effectively repair DNA novel therapeutics for and uncovered them ideal models to investigate the cellular pathways damage (21,22). However, more study is required to new tools to advance . Located just 12 contributing to longevity and disease resistance with determine if the high resistance to DNA damage in miles from NEB’s headquarters in Ipswich MA, a new direct relevance to human health. cells contributes to the low incidence of marine biotechnology institute, Gloucester Marine In addition, sea urchins are commercially fished and cancer and to understand the cellular mechanisms Genomics Institute (GMGI), is applying innovative therefore considerable data are available regarding protecting DNA. genomic technologies to marine science for their growth, survival, longevity, susceptibility to discoveries that impact human health, biotechnology At GMGI, our goal is to use sea urchins and other disease and reproductive patterns as this information and fisheries. In February, GMGI’s Science Director, long-lived marine as models to identify is essential for effective fisheries management (10). Dr. Andrea Bodnar, visited NEB to provide an overview the key and cellular pathways involved in From these data it has been noted that different of the research programs at GMGI and to present long-term maintenance of tissues and resistance of sea urchins exhibit very different natural lifespans some of her work using sea urchins as models to to cancer. Insight gained from studying exceptional in the wild. While the red sea urchin (Mesocentrotus unlock the secrets of living a long and healthy . longevity in sea urchins may reveal novel strategies franciscanus) is reported to be very long-lived, the to slow the destructive process of aging and identify purple sea urchin (Strongylocentrotus purpuratus) has new avenues for prevention or treatment of age- Understanding Extreme Longevity an estimated maximum life expectancy of more than related such as cancer. The oceans are home to many of the Earth’s 50 years and the variegated sea urchin (Lytechinus longest-lived animals with several non-colonial variegatus) has an estimated life expectancy of about Dr. Bodnar would like to thank Dr. Barton Slatko for marine and documented to 4 years (6,7,11-13). Comparisons between long-, the invitation to participate in NEB’s seminar series. live for more than 100 years (Table 1) (1–8). Many intermediate- and short-lived species provide an of these animals grow and reproduce throughout excellent model to understand mechanisms of lifespan REFERENCES 1) Butler, P.G., et al. (2013) Palaeogeography, Palaeoclimatology, Palaeoecology their lifespans with no apparent functional decline, determination and can provide insight into how these 373, 141–151. no increased incidence of disease or increase in animals avoid the process of aging. 2) Nielsen, J., et al. (2016) Science 12, 702–704. 3) Bergquist, D.C., et al. (2000) Nature 403, 499–500. mortality rate with age. A better understanding of the Aging is a complex and multifactorial process and 4) George, J.C., et al. (1999) Canadian Journal of Zoology 77, 571–580. mechanisms by which these animals achieve their there have been many theories proposed to explain 5) Munk, K.M. (2001) Alaska Fishery Research Bulletin 8, no. 1, 12–21. extraordinary life histories may reveal exceptionally 6) Ebert T.A. and Southon, J.R. (2003) Fishery Bulletin, 101 no. 4, this phenomenon at the molecular, cellular, systemic 915–922. effective defenses against the destructive process of and evolutionary levels (14). Human aging is 7) Ebert, T.A. (2007) in: J. M. Lawrence, ed., Edible sea urchins: and aging and suggest novel avenues to prevent or treat , 2nd edition 95–134. accompanied by the shortening of telomeres (caps 8) Bureau, D., et al. (2002) Canadian Technical Report of Fisheries and Aquatic human age-related degenerative diseases. that protect the ends of ), accumulation Sciences 2413, 84. 9) Ebert, T.A. (2008) Experimental Gerontology 43, 734–738. The red sea urchin is among the Earth’s longest-lived of cellular oxidative damage, and reduced ability to 10) Lawrence, J.M. (2007) Edible Sea Urchins: Biology and Ecology, 2nd animals, estimated to live for more than 200 years repair and replenish damaged tissues. In contrast, sea Edition (Oxford, UK: Elsevier) 11) Moore, H.B., et al. (1963) Bulletin of Marine Science 13, 23–53. without evidence of age-related decline and no urchins maintain their telomeres(15,16), have little 12) Beddingfield S.D. and McClintock, J.B. (2000) Marine Ecology 21, reported cases of cancer (6,7,9). Sea urchins have accumulation of oxidative damage (17) and maintain 17–40. the ability to continually regenerate lost or damaged 13) Ebert, T.A. (2010) Marine Ecology Progress Series 406, 105–120. served as model organisms for scientific research 14) Weinert B.T. and Timiras, P.S. (2003) Journal of Applied 95, for more than a century and provide a unique appendages throughout their (18). In most 1706–1716. animals, there is a delicate balance between promoting 15) Francis, N., et al. (2006) FEBS Letters 580, 4713–4717. opportunity to investigate the mechanisms underlying 16) Ebert, T.A., et al. (2008) Bulletin of Marine Science 82, 381–403. extreme longevity and negligible aging. Sea urchins cell renewal and for maintaining healthy 17) Du, C., et al. (2013) Free Radical Biology and Medicine 63, 254–263. have contributed to our understanding of important tissues, and the danger of unchecked, abnormal cell 18) Bodnar, A.G. and Cofman, J.A. (2016) Aging Cell 15, 778–787 growth that defines cancer. Notably, there are no 19) Jangoux, M. (1987) Diseases of Aquatic Organisms 3, 221–229. biological processes including fertilization, the role of 20) Robert, J. (2010) Developmental and Comparative Immunology 34, chromosomes in inheritance and the regulatory documented cases of cancer in sea urchins (19,20). 915–925. networks that guide . The The ability of sea urchins to continually grow and 21) Loram, J., et al. (2012) Aquatic Toxicology 124–125, 133–138. 22) Reinardy, H.C. and Bodnar, A.G. (2015) Mutagenesis 30, 829–839. fact that is synchronized in early sea regenerate while apparently resisting cancer holds

< The red sea urchin LONGEVITY IN NON-COLONIAL MARINE ANIMALS ( Mesocentrotus Common Name Species Oldest Recorded Lifespan (Years) franciscanus) is one of 1 the earth’s longest-lived Ocean quahog clam Arctica islandica 507 animals, potentially living Greenland shark Somniosus microcephalus 3922 for more than 200 years Marine tubeworm Lamellibrachia sp. 2503 with no signs of aging 4 and no reported cases Bowhead whale Balaena mysticetus 211 of cancer. Rougheye rockfish Sebastes aleutianus 2055 Red sea urchin Mesocentrotus franciscanus 2006,7 Geoduck clam Panopea abrupta 1688

Founded in 2013, Gloucester Marine Genomics Institute is a 501(c)3 with a mission to conduct world class marine biotechnology research which expands the regional economy. 7