Long Life and Naked Mole Rats

At 7 a.m., Minhazur Sarker is the first person to arrive in Tory Hagen’s lab on the third floor of the Linus Pauling Science Center. Hagen, a renowned researcher with the Linus Pauling Institute, studies the human healthspan. The research that takes place in his lab is focused toward a lofty goal: promoting healthy, less destructive aging processes. But though the lights are on in the long room lined with rows of countertops, at this early hour no one is hunched over in the chairs, taking notes or observing experiments.

Minhazur Sarker, an undergraduate in the College of Science, works with cell cultures in Tory Hagen's lab in the Linus Pauling Institute (Photo: Karl Maazdam)
Minhazur Sarker, an undergraduate in the College of Science, works with cell cultures in Tory Hagen's lab in the Linus Pauling Institute (Photo: Karl Maazdam)

“My father told me, ‘To get the most out of research, get there before everyone else and leave after everyone else,’” Sarker says.

And he’s following that advice, sometimes arriving even earlier than 7 a.m. and working into the evening. The first thing Sarker does when he gets to the lab is check on his cells. In a room off the main lab, he takes a flask of vibrant orange liquid out of a small refrigerator. The liquid, which resembles flat orange soda, contains the cells that Sarker’s project hinges on. By experimenting with human and rodent cells, he’s hoping to help discover a means to slow aging in humans.

A senior studying microbiology, Sarker arranged his project through the Oregon State University Howard Hughes Medical Institute (HHMI) undergraduate research program. One of the university’s most prestigious research opportunities, the institute facilitates paid research positions for undergraduate students in projects that are usually completed over the summer. While HHMI students work in all areas of the sciences, Sarker’s project draws on Oregon State’s strength in the health sciences and Hagen’s innovative research on healthy aging. When Sarker joined Hagen’s lab at the end of last school year, Hagen asked him to explore a possible avenue to promote healthier aging that began with an unlikely source — the naked mole rat.

The only cold-blooded mammal, the naked mole rat has a low metabolic rate and spends its life underground, all characteristics that contrast sharply with human life. But the naked mole rat also has something that humans have pursued for centuries: the key to longevity. These rodents, Sarker says, can live up to 30 years — 10 times the lifespan of other rats. And Hagen has an idea of what the naked mole rats’ secret might be.

Fewer calories, longer life

“When you think aging, you think of the damages that occur in the body, but people forget the other half, the body’s defense mechanisms and the way it fixes things up,” Sarker says. “Aging is two things: destructive processes and the responses.”

The quality of those response processes deteriorates over time, allowing degenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s to develop because the body’s defenses can’t keep up with the damage being done. But a process known as the heat shock protein response, which involves the refolding of proteins that are disordered by physical stress on the body, has been shown to remain active longer as a result of caloric restriction. A restricted diet like that of the naked mole rat, Hagen says, allows the body’s proteins to remain in balance longer and stimulates the heat shock protein response more often. By this means, Hagen believes, the naked mole rat may be improving its longevity.

“The only real known paradigm of increasing mean lifetime of species is dietary and caloric restriction,” Hagen says. “When you restrict calories but provide vitamins and micronutrients to maintain basic function, the species lives for an inordinately long time.”

Hagen would like to see humans take advantage of a more enduring heat shock protein response, but he’s not expecting people to live on a fraction of the calories in an average diet.

“Part of our work in healthy aging is to try to have that benefit without the burden,” Hagen says. “Part of that is to find mimics that would add nothing to the diet and certainly could increase the health span.”

Cell by cell

Under the microscope, the orange liquid becomes a field of bulbous white shapes that resemble burst popcorn kernels. The cells grow in a liquid medium until there are too many for the flask, when Sarker splits them into new containers to be used in testing or to continue growing. By this means, he’s able to keep the cells growing indefinitely.

Performing cell culture requires precision and absolute sterilization, creating a sense of pressure that Sarker believes sometimes wards off students who are interested in research.

“You learn by doing,” he says. “That’s what research is. I tell new students, you have four years to mess up in college; learn from your mistakes. Do it — screw up, mess it up — no one is going to hold it against you.”

The mimic that Hagen asked Sarker to experiment with is geranylgeranylacetone, a compound that has been safely used to treat ulcers and arthritis overseas. Sarker is testing GGA’s potential to induce a particular heat shock protein response, HSP70, by applying it to cells of the four species and then exposing the cells to stressful conditions to activate the response. By analyzing how the cells react to the stress, he hopes to determine whether the compound could be used to enhance the heat shock protein response.

Though Sarker’s project began during the summer and the HHMI program doesn’t require him to work beyond that period, he’s committed to taking the project as far as he can. During his final year at Oregon State, Sarker will continue working in Hagen’s lab.

“I have some preliminary results, but there’s a lot more I can do with it, so I really want to take ownership of it and move forward,” Sarker says. “It’s more about the process and not just about the completion and getting a result. Having a positive result is a good thing, but if you don’t get there, did you learn from it?”

Research as an undergraduate

While Sarker continues to explore whether GGA could slow the effects of aging in humans, he maintains a full schedule. In addition to working at the lab, preparing to attend medical school and running his own online business netting lacrosse sticks, he works as a tour guide for the College of Science. After spending a morning piping cell cultures into new plates and running samples, Sarker can be found walking backwards across campus with a group of prospective students and their parents in tow.

As comfortable with the campus visitors as he is in the lab, Sarker uses his own experiences to encourage younger students to take advantage of research opportunities in college.

“When you do research on campus, you’re learning, you’re helping your future and you’re getting paid,” he tells students on his tours. “That’s a triple positive, and that doesn’t happen very often, so when you find one, take it and run for it.”

Through undergraduate research programs like the HHMI, students can gain skills and experience that aren’t available elsewhere — and learn from renowned researchers such as Hagen. According to Hagen, involving students in research is a natural priority, both in his lab and at Oregon State University.

“We don’t have big barriers at Oregon State; faculty and students interact very easily,” Hagen says. “I’ve been here for 14 years and had undergraduate students in our lab pretty much all those years. It’s part of our reason for being here, showing students what a lab experience is like.”

Sarker ends his tours in front of the Linus Pauling Science Center, where he’s able to point out the floor he works on and describe how hands-on work at Oregon State has benefited his education, before heading back to the lab.

“That’s really the reason to come here, for the experiential learning,” Sarker says. “Research teaches you maturity, to be respectful, give presentations, interact with people, as well as organization and time management. These are skills you’re not going to get in the classroom.”