STEM-Talk
Episode 91: Irina and Michael Conboy explain tissue repair and stem-cell rejuvenation
// Jun 25, 2019
Our guests today are Drs. Irina and Michael Conboy of the Department of Bioengineering at the University of California Berkeley. In their lab at Berkeley, the Conboys investigate the process of tissue repair in the body in an effort to determine why damaged tissues do not productively repair as the body ages.
In today’s interview, you will hear the Conboys talk about their early research and a fascinating technique they pioneered called heterochronic parabiosis, where the couple took a young mouse and an older mouse and sutured them together so the animals blood and organs. The Conboys found that the older mouse benefited from this fusion, its aged stem cells becoming rejuvenated and its muscle tissues becoming functionally younger.
Since then, the Conboys’ follow-up research has provided fascinating insights into stem-cell niche engineering, tissue repair, and stem-cell aging and rejuvenation. In 2015, they published an important study showing that high levels of the protein TGF-β1 impaired the ability of stem cells to repair tissues. While their experiments also showed that giving old animals young blood appeared to have some benefit to old stem cells, the Conboys’ most recent work provides compelling evidence suggesting the more interesting benefits are instead produced by a dilution of harmful signals in old blood.
The research coming out of the Conboy lab has profound implications in terms of postponing the onset of age-related diseases as well as the prevention of such degenerative conditions such as Parkinson’s, Alzheimer’s, osteoporosis and sarcopenia.
Show notes:
[00:03:23] Dawn opens the interview asking Irina about her time as a gymnast in the Soviet Union. [00:03:56] Irina talks about how she became interested in biology. [00:04:36] Michael describes how he was a bit of a nerd who spent a lot of time outdoors as a kid studying bugs. [00:05:29] Ken asks what Michael’s plans were when he started his education at Harvard. [00:06:00] Ken inquires as to what it was about lab work that attracted Michael to the point where he abandoned medical school and focused on research instead. [00:06:56] Irina tells the story of her first overseas visit to Boston and how a female friend of hers had set her up with multiple dates for her visit before her plane had even touched down in the states. [00:09:06] Michael recounts the story of his first time in Moscow, where he asked Irina if she wanted to hang out. [00:10:52] Dawn mentions that after graduating, Michael got a job as a lab tech at Harvard, but eventually moved to Philadelphia to join the lab a friend of his was starting. Michael goes on to explain how he and Irina eventually became professional lab rats together there. [00:13:44] Michael explains how he would likely still be a lab tech if it were not for Irina and her desire to study aging, and how that inspired him to pursue his doctorate at Stanford. [00:15:10] Dawn asks Irina about her pursuit of a Ph.D. at Stamford in auto-immunity in the lab of Patricia Jones. [00:18:30] Dawn asks Irina to explain her discovery that Notch Signaling had the potential to regenerate aged muscle, a discovery she made during her post-doc work at Stamford. [00:21:30] Dawn mentions that Irina finished her post-doc work before Michael did, which allowed her to get work at a competing laboratory. Dawn asks if working at a competing labs created tension between the two of them. [00:24:26] Ken asks Irina what led her to look into reactivating old stem cells and whether that might delay or even reverse the onset of aging. [00:26:00] Michael talks about his inspiration for the parabiosis experiment, which involved two mice, one old and one young, being statured together. [00:30:12] Ken asks what the results of the parabiosis experiment were. [00:31:57] Ken mentions that the 2005 paper in Nature, which documented the findings of the parabiosis experiment, sparked an interesting reaction from the media that included headlines about “baby boomer vampires.” Ken asks the Conboys if they were annoyed with the overly simplistic interpretations of their study’s findings. [00:33:27] Dawn asks about Michael and Irina’s research into finding an inhibitory compound in old blood that turned out to be transforming TGF Beta 1. [00:37:44] Ken brings up Michael and Irina’s 2016 paper, published in Nature Communications,in which they described a new, more definitive, experiment than the parabiosis experiment. This blood exchange experiment, aimed to distinguish whether there was a curative property of young blood, or an inhibitory compound being filtered out of old blood, exchanged only blood between the two animals, rather than all of their organ systems. [00:40:55] Michael explains that those experiments came at a time when funding was drying up for the Conboy’s lab. He talks about how discussions with Aubrey de Grey from the SENS Research Foundation aided him and Irina with their experiments. [00:45:23] Dawn asks why Michael and Irina about their criticism of the company “Ambrosia,” a start up in Florida that claims it can combat aging by infusing plasma from young donors into its customers. [00:47:15] Ken says the coverage of Ambrosia has sparked an interesting question of whether or not young people should store their own blood for future transfusions. He asks if anyone has modeled that in mice. [00:51:46] Dawn wonders if it’s the age of a stem-cell’s environment that is the key. If so, she asks the Conboys if their research and findings are going to discourage the use of cell-based therapies to treat disorders related to aging? [00:52:45] Dawn inquires as to how the Conboy’s and their colleagues in the bioengineering department at Southern Cal are developing “youthful micro-niches” for cell and tissue transplantation. [00:54:11] Ken asks Irina to talk about her group’s 2014 paper published in Nature Communications,that showed that oxytocin in mice is vital for muscle maintenance and regeneration, and that the lack thereof leads to premature sarcopenia. [00:56:37] Irina elaborates on the comment noted by Wendy Cousins in a media piece associated with the previously mentioned paper, where she said that oxytocin could become a viable alternative to hormone replacement therapy as a way to combat the symptoms of both male and female aging. [00:58:03] Dawn notes off-label use of intranasal oxytocin is now widely used. Although there have been some human trials of oxytocin associated with mental disorders such as autism, schizophrenia and dementia, it would seem appropriate to have human trials aimed at the potential for oxytocin to prevent, slow, or ameliorate some of the undesirable consequences of aging. Dawn asks the Conboys if they know of any studies underway looking at oxytocin explicitly in the context of aging in humans? [00:59:43] Ken asks Michael if the intranasal oxytocin would be expected to yield the same benefits in muscle as a subcutaneous injection, or if the dose wouldn’t be sufficient. [01:02:33] Ken notes a variety of ways that aging can be slowed, from oxytocin to fasting, and asks Michael about a multifaceted approach to aging. [01:06:27] Ken mentions that a group working at MIT has reported benefits in mice fed lactobacillus reuteri, which has been found to upregulate oxytocin significantly, and that lactobacillus reuteri counteracts age-associated sarcopenia as well. [01:11:58] Ken asks the Conboys what scientific question they would like to answer if they were given unlimited resources and how would they go about answering it. [00:14:05] Ken asks Irina about a bumper sticker she keeps in her office that says “don’t believe everything you think.” [01:15:30] Dawn mentions that Michael and Irina have been married for more than 25 years and that although they don’t have any children, that someone dropping by their house might likely see “Sesame Street” on the TV. Dawn asks the Conboys about their fondness for “Sesame Street.”Links:
Michael Conboy UC Berkeley page