SBU study searches for proteins damaged with age

SBU study searches for proteins damaged with age

by -
0 887
Adam de Graff takes a break from the Gordon Conference on the Biology of Aging in Lucca, Italy, last year to enjoy the sights. Photo de Graff

Flecks of gray hair appear near the temples, laugh or frown lines deepen and elbows become dry and scaly. These are some of the signs of aging that people see, particularly when they’ve known family and friends for decades.

Adam de Graff, a research assistant at Stony Brook University’s Laufer Center for Physical and Quantitative Biology, however, is studying changes that occur well beneath the skin.

Specifically, de Graff, Ken Dill, a distinguished professor of chemistry and physics and director of the Laufer Center for Physical and Quantitative Biology and graduate student Michael Hazoglou looked at the proteins that are damaged by free radicals, which are released during oxidation. These free radicals are molecules that have an unpaired electron and a high chemical reactivity that can damage proteins, DNA and lipids.

When people reach 80, about half their proteins are damaged by oxidation. de Graff, Dill and Hazoglou used physics and computer analysis to look closely at protein changes. These Stony Brook scientists recently published their results in the journal Structure.

The researchers studied “how naturally occurring damage to proteins affects their ability,” de Graff said. “Such an understanding is critical, as stability is essential to their function.”

The proteins these scientists identified could become a site for targeted treatment against age-related diseases, de Graff said. Proteins operate with a simple principle: Their shape, structure and flexibility determine their function. Their stability ensures their success in their roles. Proteins have many different functions, from transporting oxygen to providing structure and  hormonal signals.

Each of these protein functions requires a certain type of architecture. Protein structure is needed for a “complete understanding of function,” de Graff said. While other researchers have explored which amino acids are the most susceptible to oxidation, de Graff and his collaborators focused primarily on the charged amino acids.

The creation of free radicals is a universal side effect of respiration. Finding a drug, however, that might make the mitochondria, or the energy producer of the cell, work without causing damage, might increase the longevity of the cell machinery and the organism.

When comparing the life expectancy of birds to rodents, birds win out, living much longer, on average, than mice or rats. Some scientists believe this might be the case because birds have “much cleaner” mitochondria, de Graff said.

Indeed, a drug that makes human mitochondria work without producing as many protein-damaging free radicals might generate human cells that suffer less age-related damage.

Their method of analyzing and studying proteins could indicate which proteins are the most vulnerable to oxidative damage, while also indicating which are the most durable.

De Graff said he and Dill studied these proteins by using a computer code they wrote, which sorts through entire proteomes. They sorted through the proteins to find the proteins most destabilized by damage. They are predicting the degree of stability loss resulting from that damage.

De Graff said he has paid particular attention to studies that demonstrate a link between lifestyle choices and longevity.

Seventh Day Adventists, who have a restricted diet that doesn’t include as much animal protein, live, on average, six to seven years longer than the rest of the population. He suggested that some of what will help people live longer will have less to do with “genetic manipulation” than it will with making better and more informed choices about diet and health. It will be helpful at a protein level to understand “why dietary intervention has an impact on how we age.”

He is also confident that, over time, researchers will develop an enhanced understanding of the interventions that will protect proteins from damage. Equally important, he believes “we will enhance our understanding of interventions that enhance our ability to get rid of this damage as it is occurring or once it has occurred.”

De Graff likened the process of keeping a biological system running over time to managing a city. In the urban setting, the mayor might take the tax dollars and use it to build roads or fix bridges. As time goes on, the available tax dollars might diminish, which increases the importance of understanding the cost of each activity with age.

De Graff, who grew up in Canada and now lives in Stony Brook, said he was interested in math from the age of 5. When he was 6, he was already doing fourth-grade math. De Graff said he practices what he preaches — he has significantly reduced his consumption of animal protein and lives a clean lifestyle.

When he was in high school, he thought he’d become a physicist or engineer. He coupled that natural talent and appreciation with a desire to understand biological systems.

Banu Ozkan, an assistant professor in the Department of Physics at Arizona State University, praised de Graff’s efforts and his results. De Graff “always finds intriguing questions and is very inquisitive,” said Ozkan. “He’s a very hard worker. Whenever I came [to the lab], during weekends and sometimes at night, I found him working.” Ozkan predicted de Graff had a bright future.

As for his work, de Graff remains excited about the possibility of collaborating on future aging-related research.

“Without an understanding of what it takes to maintain individual proteins in their healthy state,” he said, it’s hard to “understand the interactions and aging processes inside the cell.”