Researcher studies worms to reveal the fountain of youth

Assistant professor Javier Apfeld plumbs the cellular mechanisms driving the aging process in worms, uncovering insights that could increase our own longevity.Photo by Adam Glanzman/Northeastern University

In 2010, when Pres­i­dent Barack Obama spoke at North­eastern in sup­port of Martha Coakely’s guber­na­to­rial bid, he looked markedly dif­ferent from the can­di­date we’d seen on the cam­paign trail just two years ear­lier: His black hair was salted with white, his face thinner, his wrin­kles more deeply etched.

Assis­tant pro­fessor Javier Apfeld, who joined the Col­lege of Sci­ence this fall, wants to under­stand that aging process. With worms as his sub­jects, he plumbs the cel­lular mech­a­nisms dri­ving the com­plex pro­tein inter­ac­tions reg­u­lating lifespan, some of which—remarkably—have been con­served through evo­lu­tion all the way from his micro­scopic Caenorhab­ditis ele­gans to us.

“What con­trols how long an organism lives?” he asks. “I study that ques­tion in worms, which are a great model because they live only about two weeks, so I can do exper­i­ments quickly and rel­a­tively inex­pen­sively. Of course, worms are worms—they’re not mice, they’re not humans. But many of the genes that affect lifespan in worms affect lifespan in other organ­isms. Worms are, in many ways, leading the way in under­standing aging.”

In his lab at North­eastern, Apfeld manip­u­lates the worms’ genes and envi­ron­ment in an attempt to learn what fac­tors lengthen or shorten their lives—and even whether there’s a limit to how long they can live. The answers could pro­vide clues to increasing our own longevity.

A market for electrons

Apfeld didn’t so much choose the aging field as the field chose him. As a grad­uate stu­dent at the Uni­ver­sity of Cal­i­fornia, San Fran­cisco, he heard mol­e­c­ular biol­o­gist Cyn­thia Kenyon describe how worms with a muta­tion in a par­tic­ular gene had double the lifespan of those without it. “It was unbe­liev­able.” he says. “My head was exploding.”

That enthu­siasm extends to his cur­rent research: How “oxi­da­tion” and “reduction”—the trading of elec­trons between pro­tein molecules—relates to aging. He thinks of the exchange, dubbed “redox,” as a “market for elec­trons in the cell.”

“Oxi­da­tion is the process of a mol­e­cule selling an elec­tron, and reduc­tion is the process of a mol­e­cule buying an elec­tron,” he says. Many fac­tors can kick off the trade, including a change in an organism’s envi­ron­ment, such as a toxin, or its diet.

“When you work with smart and curious grad­uate and under­grad­uate stu­dents like those at North­eastern, lots of cool things can happen.

— assis­tant pro­fessor Javier Apfeld

Were that market to expe­ri­ence free fall, mayhem could ensue: Research has linked increased pro­tein oxi­da­tion to age-​​related dis­eases such as cancer, heart dis­ease, dia­betes, and Alzheimer’s and Parkinson’s diseases.

“We are trying to under­stand the causes of aging by linking the mech­a­nisms that con­trol the oxi­da­tion of pro­teins at the cel­lular level with the mech­a­nisms that deter­mine the lifespan of the whole organism,” Apfeld says.

Dig­ging deeper

It’s a daunting task. A break­through study that Apfeld co-​​authored while an instructor at Har­vard Med­ical School pro­vided one piece of the puzzle, thanks to a new flu­o­res­cent sensor tech­nology that pre­cisely mea­sures oxi­da­tion reac­tions in the cells of live organisms.

The team dis­cov­ered that a com­pound called glutathione—found in animal and plant tis­sues, including those of worms and humans—plays a very dif­ferent role in redox than orig­i­nally thought. Rather than acting as a buffer against oxi­da­tion, it may amplify or temper mes­sages con­trol­ling the process.

Glu­tathione, it turns out, func­tions as a kind of mol­e­c­ular micro­phone.

The finding could change the course of research into the role of oxi­da­tion in age-​​related dis­eases. It could also have impor­tant impli­ca­tions for treat­ments, including the use of antiox­i­dant supplements.

At North­eastern, Apfeld will dig deeper into causes: He is inves­ti­gating what drives the glu­tathione com­mu­ni­ca­tion system and how oxi­da­tion changes the func­tion of the affected pro­teins. “When you work with smart and curious grad­uate and under­grad­uate stu­dents like those here,” he says, “lots of cool things can happen.”

ORIGINAL: Northeastern U

by Thea Singer

March 22, 2016