Ovaries are the fastest aging organ in the body, but the least studied organ in aging research.
The impact of aging ovaries on a woman's fertility are well known, but aging ovaries-which shrink from the size of a kiwi to a kidney bean-also have much wider impacts on a woman's health in the later decades of life. The earlier the ovaries age, the more likely a woman is to develop heart disease, dementia, depression, glaucoma, and other diseases, and die earlier.
"The ovary is an endocrine organ and influences aging in the entire body," says Yousin Suh, the Charles and Marie Robertson Professor of Reproductive Sciences (in Obstetrics & Gynecology) who joined Columbia in 2017 to push ovarian aging research to the forefront of geroscience.
Columbia researcher Yousin Suh says lessons learned from studying aging ovaries could help women and men live longer and healthier lives. Photo by Jörg Meyer for Columbia University Vagelos College of Physicians and Surgeons.
"By delaying ovarian aging, we could live longer and healthier lives," she says.
Suh's latest study, a comprehensive comparison of young and old human ovaries published in Nature Aging, has already revealed some surprises, including some that may lead to benefits for all aging people. Based on some of these findings, she has already launched a clinical trial, VIBRANT.
In this edited interview, she discusses her personal reasons for studying ovarian aging and her recent breakthroughs in this long-neglected field.
How did you end up working on aging?
Science always fascinated me since I was a little girl. I grew up in Korea, studied biology at a university in Korea, and after that I came to the United States to pursue my PhD and then postdoc before going back to Korea for about seven years. That was when I started becoming interested in aging research, but it was challenging to become independent as a woman in science there in the 1990s, so I decided to come back to the United States to pursue my independent career.
Initially you studied aging in elderly people, right?
Yes, when I was at Albert Einstein College of Medicine, I studied genetics of human longevity by studying centenarians, people who live over a hundred years, and I also studied basic mechanisms of aging-related diseases. The common hypothesis is that since aging is the driver of all chronic diseases, why don't we target the root cause of those diseases, and that is the fundamental mechanism of aging. It's been demonstrated time and time again that if you target the basic biology of aging, you can make animals live longer and healthier lives. The question is whether that's really relevant to human aging. So that's what I was addressing in my lab with human genetics and functional genomics.
Why did you start studying ovaries?
In 2017, I met Dr. Mary D'Alton, who is the chair of obstetrics and gynecology at Columbia's Vagelos College of Physicians and Surgeons. We saw an alignment between the genetics and genomics research Columbia is known for and the work that I was doing; the result was a new, innovative reproductive aging program. This is an area where almost nothing had been done, so it's heavily understudied and underfunded, but incredibly important.
Coincidentally, I was going through a tough time because of my own reproductive aging. I was in the perimenopausal state and it was really the most difficult part of my life. My whole world went upside down, my brain refused to work, my immune system collapsed, I got sick all the time. Putting it all together, I thought this might be a calling. I loved the idea of doing something new and very important to help fellow women going through the same thing. This is a condition that one hundred percent of women go through.
Women's health has long been underfunded. Were you worried about getting grants for your new work?
Luckily, when I started focusing on this area, suddenly there was some funding available. It was the first time in the history of the National Institute on Aging that they put out a request for applications on aging in reproductive tissues. At the same time the Global Consortium for Reproductive Longevity and Equality [at the Buck Institute] started up, and I received research funding from this consortium as well.
This is an area that's been totally ignored historically in biomedical research and clinical development, but suddenly there was an increase in awareness that this is so unfair, and we need to change. So, for me it was just a lucky moment. All the stars aligned.
What's different about studying ovarian aging, compared to your earlier work, and what have you found so far?
When you're looking at human aging, you're usually comparing 20-somethings and people 65-plus, but when you're talking about aging in the ovary, the "elderly" category starts around age 35. Aging occurs in the ovary 15 or 20 years earlier than in any other tissue. "The big surprise was that there's nothing special about how ovaries age."
In our latest research, we compared ovaries in women in their 20s versus 40s or 50s, and the big surprise was that there's nothing special about how ovaries age. The same genetic programs and molecular signals you see in an old brain or heart or kidney in your 60s, you see in this tiny organ in your 40s.
The good news is that means geroprotective drugs, which delay aging in animals, could be used to delay aging in the ovary.
Whenever you mention ovarian aging, people think about fertility, but that's not your main focus, is it?
People often say, 'Oh my God, who wants to have a baby or have periods in their 60s?' But they've gotten the wrong message, that's not what we are saying. We are saying that by delaying aging in the ovary, you improve health in the whole body.
And we're not just helping women, we're helping men too, because the aging mechanism is the same in every human organ. Because of that, the human ovary could be a rapid test platform for geroprotective drugs. We already know these drugs make mice live longer and healthier, but are they really going to work in humans? We can't set up trials in people to see if the drugs help people live longer; it would take decades to get the results.
But by testing the drugs' effects on the ovary, we can see if they slow aging in three months, not three decades, because aging is compressed there. That's the idea behind our VIBRANT study, which is testing rapamycin's ability to delay ovarian aging in women.
We are testing the drugs in the ovary, but at the end of the day, we will find a way to delay aging in everyone.
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Additional information
Yousin Suh, PhD, is the Charles and Marie Robertson Professor of Reproductive Sciences (in Obstetrics and Gynecology) and professor of genetics & development at Columbia University Vagelos College of Physicians and Surgeons.
