Einstein Researcher Seeks Secrets of Aging

Research that may someday enable medicine to extend human lifespan is, ironically, being conducted by a 29 year-old Einstein scientist in the early stages of his career.

Dr. Simon Johnson, a postdoctoral researcher in genetics, was recently named winner in the Translational Medicine category of the Science & SciLifeLab Prize for Young Scientists. The distinction included the online publication of his research essay, "A Novel Target for Pharmacological Intervention in an Untreatable Human Disease," in Science.

Dr. Simon JohnsonDr. Johnson's research used a mouse model to examine whether rapamycin, an immune modulating drug that has been prescribed for decades, could reduce the effects of Leigh syndrome, a childhood mitochondrial disease for which there is no effective treatment. Diseases such as this result from failures in mitochondria, the compartments within eukaryotic cells that supply their energy, control their growth and death, and perform other vital tasks.

Although rare, Leigh’s disease is devastating. Characterized as a disease of the brain and spinal cord, its wide-ranging symptoms include seizures, lactic acidosis, and muscle debilitation within a year of a child’s birth. Death, often from respiratory failure, typically occurs by age 6 or 7.

The research Dr. Johnson is now doing in the lab of Dr. Yousin Suh, professor of genetics and of medicine, and a member of Einstein’s Institute for Aging Research, builds on work he had previously done at the University of Washington that explored the relationship between genetic background and response to caloric restriction (CR), the reduced intake of calories without malnutrition. While scientists already knew that CR can extend lifespan, Dr. Johnson wondered what the genetic makeup is that determines how an organism responds. Through his earlier research, he had found that yeast strains with greater lifespans on CR also displayed differences in genes determining mitochondrial function. He then sought to determine if CR — or an intervention mimicking it — might be associated with mitochondrial function, and with greater lifespan, in mammals.

Dr. Yousin SuhTo address this question he and his colleagues examined a type of genetically altered mouse model of Leigh syndrome. Untreated, these mice live an average of 50 days, while similar wild mice have a lifespan of 20 to 30 months. Instead of subjecting the mice to CR, Dr. Johnson used rapamycin, a CR “mimetic” that inhibits a protein responsible for nutrient sensing and signaling among cells. With daily injection of rapamycin, the maximum lifespan of the Leigh syndrome mice was increased over 300 percent — an unprecedented finding in a disease model where no effective interventions exist. Neurological symptoms were also reduced; at death, some animals did not display any signs of advanced degeneration. The findings might someday lead to the development of new therapies for Leigh syndrome and other mitochondrial disease. "While that potential was an unexpected outcome, Dr. Suh and I are now working with clinical collaborators, testing rapamycin in human patients who have mitochondrial disease," said Dr. Johnson.

He added, "My primary area of interest is aging research, and this is not really an aging study but the data from our yeast screen took us to mitochondrial disease." He believes his work also has broader implications.

"Our work demonstrates that using lifespan as an endpoint, even in yeast, can provide a great deal of insight into how organisms function or fail to function," he said. "The science of aging is an incredibly complex and difficult area to study. But if we can better understand what happens in the aging process, we can better understand all fields of biology."

Dr. Suh explains the potential impact of her colleague's work this way.

"The pathway Simon is focusing on is relevant to multiple diseases. That's one of the things that make the study of aging so exciting."

She added, "We're looking at one of the root factors of health. If we combat the process of aging, we can combat the process of disease in general."

Ongoing work in the lab includes looking at discoveries in humans and modeling them in mice.

Meanwhile, Dr. Suh finds Dr. Johnson's skills a perfect complement to those of her lab.

"His expertise, especially in translating knowledge to the mouse model, is enriching for us. And in his current work here, he's learning from Einstein’s experience in human studies. In many ways, we're educating each other."