The Science of Senescence

MD-PhD student Ayumi Nakamura takes on the curious connection of microRNAs and premature aging.

Visiting Osaka, Japan, Ayumi Nakamura is never disappointed. She sees them all the time – 90-year old women and men riding bikes, carrying groceries, walking briskly to shops along busy thoroughfares. She’s lived there before. She visits her grandparents in Osaka every year, and what she sees there, she sees here less often. In Japan, Nakamura witnesses a commonly found vitality and healthfulness among the older population.

Some chalk up these differences to genes and diets. Nakamura, though, is inspired to dig deeper. She’s an MD-PhD student currently working on cell death and the genetic underpinnings of senescence -- the process of deterioration that comes with aging. Her work earned her one of only two slots as a presenter at the American Physician Scientist Association’s annual meeting this year.

We sat down with Ayumi for a student profile to discuss her work, her path to UNC, and what inspired her to pursue an MD-PhD with a concentration on aging and premature aging disorders.

Name: Ayumi Nakamura

Birthdate: March 20, 1986

Hometown: Osaka, Japan

Education: BS in biology, BA neuroscience at UVA / MD-PhD student at UNC

Dissertation: Exploring the role of microRNAs in premature aging

Goal: Understanding the pathogenesis of aging

Mentor: Mohanish Deshmukh, PhD, department of cell biology and physiology

Hobbies: ceramics, pottery, running, cooking

Extracurriculars: John B. Graham Medical Research Society / past co-president, Internal Medicine and Pediatrics Interest Group

Awards: Top abstract, presenter at the American Physician Scientist Association Meeting /NRSA F-30 Award for MD-PhD students / Gertrude B. Elion Mentored Medical Research Award / Glenn-AFAR Scholarship in the Biology of Aging / RIKEN Center for Developmental Biology Travel Fellowship /Gordon DeFriese Aging Research Award

Publications

A shift to organismal stress resistance in programmed cell death mutants, PLoS Genetics, September 2013

A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells, Proceedings of the National Academy of Sciences, March 2011

Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene, Proceedings of the National Academy of Sciences, July 2009

Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde, Cancer Research, December 2007

History:

“My dad being a researcher had a great influence on me. I would always go into his lab when I was in high school or home from college, and he’d show me cells and how to culture them. I really enjoyed this. My mom had been a news anchor on national television in Japan. She would always help me become a better writer, which definitely has aided me in grad school.”

Post-baccalaureate stint:

“After graduating from UVA, I went to the University of California-San Francisco to do a couple years of research in the lab of Cynthia Kenyon, who is very well-known for her research on aging.

“There, as a research technician, I studied the role of a protein called progranulin in frontotemporal dementia, the second-most common cause of dementia in patients who are 65 or younger. We used the research model organism C. elegans – the nematode. We discovered that nematodes lacking progranulin were resistant to various environmental stressors and had altered kinetics of programmed cell death.

“During my time in the Kenyon Lab, I worked directly under an MD-PhD professor. I was able to see patients diagnosed with neurodegenerative diseases in her clinic, and I think this experience solidified my interest in working with patients.”

Why UNC?

“While meeting people in the UNC MD-PhD program, as well as the PIs here, I found everyone to be so collaborative and willing to help students do great work. The program directors for the MD-PhD program are really wonderful and are more than willing to help us any way they can.

How does the MD-PhD program work?

“The MD-PhD program is designed in such a way that we complete the first two years of medical school (primarily coursework), then we do our thesis work in graduate school for about 4 years. And then we go back for the last two years of medical school. After my second year of medical school, I joined Mohanish Deshmukh’s lab. During graduate school, I’ve also been able to work in the hospital and see patients in the Neuroscience Intensive Care Unit and the Medical Oncology Unit, which have been absolutely wonderful experiences. I’m just about done with my third year of PhD work. When I’m finished with that – hopefully by next March but maybe the year after – I’ll go back to the third and fourth years of medical school when I’ll see patients.”

Why the Deshmukh lab?

“I joined the Deshmukh Lab partly because of my previous research in cell death, which is what Mohanish works on. Another reason was his focus on the nervous system. [Deshmukh is part of the UNC Neuroscience Center.] The brain was something I was actually kind of afraid of. When I was younger, neuroscience was the last thing I wanted to do. The brain was so hard to understand, and in a way I was put off by all the unknowns in such a complex organ. But now I love it. I’ve embraced it, and the complexity is one of the things I love about studying the brain.

Why aging research?

“If you look at the average life expectancy of people in different countries, Japan is in the top three. Even though I mostly grew up in Chapel Hill, I try to go back to Japan every year to visit my grandparents. Just walking through streets, you see 80-90 year olds on bicycles, walking around, doing their thing. It just amazes me. Why are they able to live such a long time? I began to wonder about what governs longevity.

“Also, during 9th grade biology we were randomly assigned a disease to study and present in class. Mine was Werner syndrome, which I had never heard of. Essentially, it’s a rare premature aging disorder. People look fine in their teens and 20s, but by the time they’re 40 or 50 they look like 80 or 90.

“I found a picture of a woman with Werner syndrome, and that picture was implanted in my brain. She was in her forties but looked at least 80. But it isn’t just about looks. Physiologically, these people are older. They have shorter lives. They lose hair and are more susceptible to age-related diseases, such as cancer.

“I also learned about another premature aging condition called Hutchinson-Gilford Progeria Syndrome. This happens in kids. These patients don’t suffer from learning disabilities or age-associated neurodegenerative diseases, something that was fascinating to me.”

Your research?

“We study the role of microRNAs in aging and premature aging disorders. A microRNA is a short piece of RNA that targets the end of genes to block their expression in cells throughout the body.

“A postdoctoral fellow in the lab, Vijay Swahari, generated a mouse that overexpressed a certain microRNA, and the results were intriguing. These mice develop features of premature aging within two months of age – things like wrinkled skin, shortened lifespan, loss of hair, and reduced body weight. Right now, we are figuring out the mechanism by which this microRNA induces aging.”

The future?

“This summer, I’ll be presenting this work at a conference in Spain sponsored by the International Cell Senescence Association. I am also planning a week-long trip to Alaska with my husband, so that should be exciting!

“I’m hoping to graduate next March. We are planning to submit our papers soon and, hopefully by that time, our papers will be published. I am also currently working on 3 first author and co-first author manuscripts. Then, I’ll move onto the last two years of medical school. After that I hope to do my residency in neurology or internal medicine. Premature aging disorders are really rare. But seeing patients with progeria is something I’d like to do.”

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