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Fly hearts could hold secrets to human heart aging

Ames Tribune - 1/12/2020

Researchers at Iowa State University are looking at the tiny hearts of fruit flies to unlock the secrets to keeping a human young at heart -- or at least the factors that make the human heart age.

Led by Hua Bai, assistant professor of genetics, development and cell biology at the university, the study explores the factors that cause aging in the heart muscles of fruit flies.

While the tube-shaped fly heart is minuscule by comparison, the two species' hearts age in a similar way.

Like humans, the cardiac muscles of the fruit fly begin to contract with less strength and regularity by middle age. For a fruit fly, that is at about 40 days.

"Definitely the contractions slow down, and this is a major change in the aging heart including in mammals," Bai said.

According to Bai, the adult life of the fly is generally about 70 to 80 days. This allows the research team to repeat its experiments many times over a short period of time.

The small size also makes them an easy subject to maintain; Bai has thousands of them sitting in vials on his desk.

Bai said a commonly accepted theory is that the heart begins to age as the process of autophagy slows down. Autophagy is a "cleanup" process that removes damage or waste from cells, and as it slows down, more of that waste is left in the cells.

The three-year study explored counteracting the factors that slow the autophagy process and cause the heart to age.

"We started doing chromosome manipulation, or DNA manipulation to identify the protein causing the drastic change," Bai said.

Two proteins involved in the function of autophagy are mTOR Complex 1 and mTOR Complex 2. The study began by focusing on Complex 1, which must be reduced to promote autophagy. However, the research team discovered a closely related protein -- Complex 2 -- that could also be used.

"It took a lot of work to identify this unknown pathway," Bai said.

Bai's research found that by boosting the amount of Complex 2 in the cell, autophagy was increased and the aging of the cardiac muscles was slowed.

According to Kai Chang, a graduate student who works in Bai's lab and was the lead author of the research paper, targeting the Complex 2 protein could be key in developing medications for heart disease in humans.

"Elderly people have a higher change or developing heart disease," she said. "By targeting the mTOR pathway this might be beneficial in finding a medical target for treating this disease."

While removing a fly gene to study its function is fairly simple, the possibility of the practice in humans or other mammals is far more difficult, Bai said. The study is just beginning to explore the future of its use in human medicine.

According to Bai, many heart medications involving the pathways have been focused on Complex 1. If development of medication using either protein continues, he said, researchers must be careful to avoid some serious side effects.

"The drug may have a side effect given that the two pathways operate very differently," Bai said. "One, you want to reduce, and on the other hand want to boost Complex 2."

Going forward, Bai and Chang said they will be switching gears to research the mitochondria of heart cells and how they are affected by stress and aging.

"The animal in the wild is always facing environmental change, challenge or stress," Bai said. "They have a way to cope with this by activating different cellular responses."

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