The research fills in gaps in how scientists understand the links between heart health and other tissues and could inform the development of new therapies in human medicine, said the senior author. The new study, published in the journal Nature Communications, also covers new ground in the function of a poorly understood organelle called the peroxisome, which may play a major role in how organisms age.

"We were thinking outside the heart for this paper," the author said. "We wanted to find out if other tissues affect cardiac function during aging. There is significant data suggesting that liver function actually is a risk factor for cardiac disease. A patient with a lot of liver dysfunction often develops cardiac disease. This is a concern because you may have two diseases that you have to deal with for these patients."

But the author said no direct link between liver and heart disease has emerged in experiments, leaving medical professionals unsure if the two factors share a causal relationship or if there's simply a correlation. The lab attempted to fill that gap by studying the interaction between liver disease and the function of cardiac muscles in flies.

In the new experiments, the researchers manipulated various genes governing liver function in flies to see how that would affect heart health as the flies aged.

The authors show that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. They show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia.

"Our findings demonstrate we can protect the liver of old animals and maintain the health of the heart without doing any direct intervention on the heart tissue," said a graduate student and the lead author of the study.

Much of the genetic work the researchers conducted focused on peroxisomes, understudied organelles inside cells that regulate key lipid metabolic processes and detoxification critical for brain and liver function.

The authors further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. They term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity.

"Looking at all the biology literature, we don't know much about how peroxisome function changes in aged animals," the senior author said. "We show that peroxisomal protein import function is significantly impaired in aged flies. Research like ours could open up another new field to study how peroxisomes regulate tissue aging."

The author said although flies appear to be highly dissimilar to humans, human medicine still has much to gain from studying fly biology. For instance, the functions of a fly's liver and heart share many similar functions with the human liver and heart.

https://www.news.iastate.edu/news/2020/06/10/liverheart

https://www.nature.com/articles/s41467-020-16781-w

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fimpaired-peroxisomal&filter=22