Pet parrots often outlive their owners, and Vanderbilt researchers want to know why because uncovering the biological mechanisms behind exceptional longevity could one day help safely extend the lives of humans.

With the support of a new $1.3 million grant from the W.M. Keck Foundation, Vanderbilt biologist Gianni Castiglione is taking a bold approach to aging research: reverse-engineering how birds live three to four times longer than similarly sized mammals to identify safe, effective genetic targets for human aging therapies.

For years, research into aging has focused on how antioxidants protect cells from oxygen-related damage, which is a major contributor to aging.

Birds carry a mutation that alters their antioxidant response. Though this mutation may help ease aging in birds, it would be fatal in humans. “Birds are thriving despite having a mutation that, in mammals, would be lethal,” said Castiglione, assistant professor of biological sciences and of ophthalmology and visual sciences.

“A lot of drugs try to turn on this antioxidant response to help slow disease progression, but if you turn it on too strongly, it can trigger dangerous side effects, including an increased risk of cancer,” he said.

While over-activating this response can be fatal in mammals, birds seem to have solved this puzzle. “Evolution’s already done this for us,” he said. “Let’s just reverse-engineer what it did.”

Castiglione is working with several Vanderbilt researchers who bring essential expertise to the project, including two key collaborators: Nicole Creanza, assistant professor of biological sciences, who maintains a zebra finch colony that will be used to test his research findings; and Allison Walker, assistant professor of chemistry and biological sciences, who applies machine learning to analyze complex genetic network patterns.

“We anticipate these rewired gene networks in birds are so convoluted that you need a machine learning approach to find all the patterns,” Castiglione said. “Those are not trivial to execute, so having her expertise as we go forward will be critical.”

This is Vanderbilt’s third Keck Foundation award in three years. As with past awards, Research Development and Support, based in the Office of the Vice Provost for Research and Innovation, supported numerous stages of Castiglione’s Keck proposal.

“They really helped me with clarity and communication, meeting proposal deadlines and adhering to required formatting,” Castiglione said. “It culminated in a presentation to the foundation … probably the most polished presentation I’ve given since my Ph.D. defense. I can’t stress enough how much they helped. I don’t think I would have succeeded if it wasn’t for their assistance.”

Castiglione’s experience reflects the coordinated support Vanderbilt aims to provide, said Elizabeth Zechmeister, interim chief research officer and senior associate provost for research and development.

“The Keck Foundation award demonstrates the value of sustained collaboration, from the strength of a researcher’s innovation to the execution of a competitive proposal,” she said. “Research Development and Support plays a critical role in that process, working closely with faculty to navigate opportunities like this one. Dr. Castiglione’s success is a testament to both his vision and the university’s commitment to enabling high-impact, interdisciplinary research.”

For Castiglione, who joined Vanderbilt three years ago, the Keck Foundation award is a major milestone, which he attributes in part to the university’s culture of interdisciplinary collaboration.

Castiglione and his team are exploring new directions in aging research by collaborating with experts from a wide range of disciplines across campus. “We’re drawing on these different disciplines, and that’s promoted here, rather than trying to fit into a box,” he said. If their efforts succeed, future generations may not just admire the longevity of parrots, they may finally match it.

Source: https://news.vanderbilt.edu/2025/07/16/vanderbilt-biologist-receives-1-3m-keck-grant-to-study-what-birds-longevity-could-mean-for-human-aging/