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Scripps Florida Scientists Identify Gene that Plays a Surprising Role in Combating Aging

JUPITER, FL, July 17, 2014 – It is something of an eternal question: Can we slow or even reverse the aging process? Even though genetic manipulations can, in fact, alter some cellular dynamics, little is known about the mechanisms of the aging process in living organisms.

Now scientists from the Florida campus of The Scripps Research Institute (TSRI) have found in animal models that a single gene plays a surprising role in aging that can be detected early on in development, a discovery that could point toward the possibility of one day using therapeutics, even some commonly used ones, to manipulate the aging process itself.

“We believe that a previously uncharacterized developmental gene known as Spns1 may mediate the aging process,” said Shuji Kishi, a TSRI assistant professor who led the study, published recently by the journal PLOS Genetics. “Even a partial loss of Spns1 function can speed aging.”

Using various genetic approaches to disturb Spns1 during the embryonic and/or larval stages of zebrafish—which have emerged as a powerful system to study diseases associated with development and aging—the scientists were able to produce some models with a shortened life span, others that lived long lives.

While most studies of “senescence”—declines in a cell's power of division and growth—have focused on later stages of life, the study is intriguing in exploring this phenomenon in early stages. “Mutations to Spns1 both disturbs developmental senescence and badly affects the long-term bio-chronological aging process,” Kishi said.

The new study shows that Spns1, in conjunction with another pair of tumor suppressor genes, beclin 1 and p53 can, influences developmental senescence through two differential mechanisms: the Spns1 defect was enhanced by Beclin 1 but suppressed by ‘basal’ p53. In addition to affecting senescence, Spns1 impedes autophagy, the process whereby cells remove unwanted or destructive proteins and balance energy needs during various life stages.

Building on their insights from the study, Kishi and his colleagues noted in the future therapeutics might be able influence aging through Spns1. He noted one commonly used antacid, Prilosec, has been shown to temporarily suppress autophagic abnormality and senescence observed in the Spns1 deficiency.

The first author of the study, “Aberrant Autolysosomal Regulation Is Linked to The Induction of Embryonic Senescence:  Differential Roles of Beclin 1 and p53 in Vertebrate Spns1 Deficiency,” is Tomoyuki Sasaki of TSRI. Other authors include Shanshan Lian, Jie Qi, Sujay Guha, Jennifer L. Johnson, Sergio D. Catz and Matthew Gill of TSRI; Peter E. Bayliss of the University Health Network, Toronto, Canada; Christopher E. Carr of the Massachusetts Institute of Technology; Patrick Kobler and Kailiang Jia of Florida Atlantic University; and Daniel J. Klionsky of the University of Michigan. The paper can be accessed at http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004409

The work was supported by The Ellison Medical Foundation, Glenn Foundation for Medical Research, A-T Children's Project), the National Institutes of Health (NIH) National Institute of Aging (AG022641) and the National Institute of General Medical Sciences (GM053396, GM101508).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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