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New grant aims to improve understanding of aging differences between females and males

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PROVIDENCE, RI [Brown University] — At five years, $12.5 million grant from the National Science Foundation will enable researchers from across the country, including three from Brown University, to identify mechanisms that drive differences in how males and females age.

The researchers will use the grant to create the IISAGE Biology Integration Institute, drawing experts from various fields to work together to determine how multiple biological processes contribute to differences in aging between the sexes and uncover their evolutionary histories.

Little is known about how or why females and males of different animal species age or why one sex outlives the other, said Erica Larschan, an associate professor of molecular biology, cell biology and biochemistry at Brown’s Warren Alpert Medical School. The researchers from Brown will focus on questions related to gene regulation.

“How does the genome actually drive those differences between males and females?” asked Larschan, a co-principal investigator on the grant. “Obviously sex chromosomes are different between males and females, but are sex chromosomes really driving these differences in lifespan and health span? We’re also looking at metabolism and DNA damage: How do all of these things work together?”

Larschan said that fruit flies, the primary models for study in her lab, are good subjects for aging research in part because they only live for about 40 days. Not only do male and female fruit flies age differently, she said, but like humans, they also have X and Y sex chromosomes. Larschan will bring to IISAGE her expertise in gene regulation processes on fruit fly X chromosomes.

Ashley Webb, a Brown assistant professor of molecular biology, cell biology and biochemistry, researches mice to understand the molecular mechanisms of stem cell aging in mammals. Webb is also a co-principal investigator on the grant.

“Ashley has identified some differences between the sexes already that we’re building off of in this grant,” including a recent paper in the journal Nature Aging that reported on a specific feature of aging in the hypothalamus of female mice, Larschan said.

Larschan and Webb are affiliated with the Brown Center on the Biology of Aging, which aims to understand the biological mechanisms of aging and age-related diseases to develop interventions to improve the human health span. Other IISAGE investigators from partner institutions bring expertise with turtles, lizards and fish, among other animals.

“The idea is to look at commonalities across these species in terms of how males and females age differently,” Larschan said. “They all have differences between males and females in lifespan, and we’re interested to see what actually drives those differences.”

While the IISAGE partners will collect only non-human animal data, understanding aging differences in other species can potentially impact how humans approach aging and care, said Nicole Riddle, an associate professor of biology at the University of Alabama at Birmingham and the grant’s principal investigator .

“There are so many implications that aging has, and for us to have an opportunity to investigate how we could manipulate aging — be that through lifestyle changes or even medications — we could be primed to unlock the most robust understanding of aging we’ve yet known,” Riddle said.

The third member of the Brown research team is Ritambhara Singh, an assistant professor of computer science who uses artificial intelligence to develop machine learning models that will use datasets to predict what is driving differences between males and females. Including scientists with expertise outside of biology is a critical feature of the grant, Larschan said.

“The NSF wants to bring people together from different fields because for a long time, people were siloed,” Larschan said, adding that collaboration is key to scientific progress.

In addition to Brown and the University of Alabama at Birmingham, researchers involved in the IISAGE Biology Integration Institute will come from Michigan State University, Cornell University, Marquette University, University of Houston, University of Maryland and the University of Kansas.

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