Vocal changes in birds may predict age-related disorders in people, study finds

University of Arizona neuroscientists studying the brains of songbirds have found that aging alters the gene expressions that control the birds' song. The finding could lead to earlier diagnoses and better treatments for human neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, which are known to hinder vocal production in their early stages.

The study, published in the journal Neurobiology of Aging, found that networks of interacting genes, in a region of the bird's brain involved with singing, dramatically change as the bird ages. At the center of these networks are "hub genes" that drive activity of many other genes. A better understanding of the hub genes could be crucial to developing treatments for age-related disorders.

"If you could make a drug that could influence a particular hub gene, you might potentially influence hundreds of other genes around it and see a macroscopic effect," said lead study author Charles Higgins, an associate professor in the Department of Neuroscience and the Department of Electrical and Computer Engineering and a member of the university's BIO5 Institute. "That could be a drug that could slow Alzheimer's disease, for example."

The study is the latest to investigate the link between vocal production and aging. Senior study author Julie E. Miller, also an associate professor in the Department of Neuroscience, has studied those connections for years using zebra finch songbirds.

"There is some hopeful news in that the bird is still able to produce the song behavior, even with the genetic changes, and it suggests that there are also some ways that the bird is adapting to what's going on in the brain," said Miller, who has a shared appointment in the Department of Speech, Language and Hearing Sciences and is a member of the BIO5 Institute. "This might offer resilience strategies for humans."

Zebra finches, native to Australia, have a strikingly similar-looking brain to humans', particularly the area known as the basal ganglia, which is used for motor function, including speech, Miller said. The finches also develop their birdsong by mimicking their parents and other birds around them – the same way humans learn to speak.

Perhaps most importantly to researchers, the birdsong is also a measurable marker for changes in the brain, allowing scientists to see how the song's pitch, volume and intensity change along with other factors.

For their latest paper, Miller and her colleagues recorded the songs of 36 birds, ranging widely in age, and studied how the genes associated with singing began to behave differently as the birds grew older.

They found that the gene networks start as vast arrays of activity in younger birds before thinning out into just a few single genes as the birds get older.

Miller said she hopes further research can shed more light on the changes to the hub genes as the finches age.

"Really, the logical goal is to try to understand whether these hub genes are important, what do they do to the song, and, if we manipulate their expression, can we prevent or slow down the aging process that affects our vocal communication?" she said.

Other researchers on the paper included Sri Harsha Vishwanath, a graduate research associate in the School of Animal and Comparative Biomedical Sciences; Fiona McCarthy, a professor of animal and comparative biomedical sciences; Michelle Gordon, a former undergraduate student in Miller's lab; and Beate Peter, an associate professor at Arizona State University.

The study was supported by the National Institute on Aging of the National Institutes of Health under Award Nos. P30AG019610 and P30AG072980 to the Arizona Alzheimer's Disease Research Center, via a sub-award to J.E. Miller. The work was also supported by the Arizona Department of Health Services and the state of Arizona under ADHS Grant No. CTR057001.