Health News for Senior Citizens

Health News for Seniors

Hope for millions of senior citizens facing heart failure found in new research

Adding protein vinculin helps fruit flies extend lives 150%

fruit flyJune 19, 2015 – Millions of senior citizens threatened by heart failure, a disease of aging marked by a weak pumping heart, could possibly see their lives significantly extended by the protein vinculin. At least there is the hint of this possibility in new research published this week.

The new findings about the role of vinculin, the researchers say, could pave the way to treatments that extend the lives of 8 million people in the United States over the next decade.

Most strikingly, the federally funded study found that fruit flies whose genes were induced to precision-boost vinculin production only in the heart, sparing other organs, survived, on average, 150 percent longer than their vinculin-deficient counterparts.

The research was conducted in fruit flies, rats and monkeys by scientists at Johns Hopkins, UC San Diego, and other institutions.

It reveals that levels of a protein called vinculin increase with age to alter the shape and performance of cardiac muscle cells — a healthy adaptive change that helps sustain heart muscle vitality over many decades.

Specifically, they discovered that the contraction function of the hearts of fruit flies is greatly improved in those that over produce vinculin, which also accumulates at higher levels in the hearts of aging monkeys and humans.

 

In addition, flies genetically programmed to express elevated levels of vinculin lived significantly longer than normal fruit flies.

The new study attributes the longer life of the flies to the improved contractile function of the heart due to the presence of more vinculin, which helps with the structure of the heart and connects heart muscle cells.

This work is published in the June 17 issue of Science Translational Medicine.

Heart disease is the leading cause of death globally and advanced age is a primary risk factor.

“With the average age being projected to increase dramatically in the coming decades, it is more important than ever that we understand and develop therapies for age-related heart failure,” said Adam Engler, a bioengineering professor at UC San Diego and senior author on the paper.

“The results of this study implicate vinculin as a future candidate for therapy for people at risk of age-related heart failure.”

For example, if additional research supports these new findings, targeted gene or drug therapies related to vinculin and its network of proteins could be developed to strengthen the hearts of patients suffering from age-related heart failure.

“More than 80 percent of protein groups found in flies, including vinculin network proteins, are similar to those found in rats and monkeys,” said Gaurav Kaushik, lead author on the study. He worked on this project as a bioengineering Ph.D. student in Engler’s lab at UC San Diego and is now a postdoctoral researcher at Harvard Medical School.

“We chose to focus on the proteins that naturally increase in expression in the aging hearts of flies, rats and monkeys. Since deletion or mutation of these proteins can lead to cardiomyopathy in patients, we wondered if their age-related up regulation was beneficial to the heart. Moreover, would overexpressing them improve heart function?”

The researches genetically modified fruit flies to overexpress proteins, including vinculin.

Remodeling the heart

The human heart is capable of functioning for decades despite the fact that few new heart cells are generated over the course of a lifetime, indicating that alterations in gene expression, known as “remodeling events” help to maintain heart function with age.

“Because renewal of heart cells is limited, maintenance of the heart may depend on remodeling events over time,” said Engler. “Identifying which events are conserved within and between organisms and which result in improved heart function is difficult but could be incredibly valuable.”

That’s one of the tasks the researchers set out for themselves. Engler continues, “Within any muscle, the contractile structures become more disordered with age. In heart muscle, vinculin is needed to preserve that structure by holding it together. By performing a kind of open-heart surgery on the flies that overexpressed the protein, we were able to see that the longer life of these flies was due to improved heart muscle function.”

In the study, 50 percent of vinculin-overexpressing flies lived past 11 weeks, to a maximum of 13 weeks. In contrast, 50 percent of control flies only made it to four weeks old and none lived past eight weeks.

“Fruit flies only live for a few weeks which makes them an ideal model for studying aging,” Engler explained.

 “The heart is an amazingly resilient organ but one that generally doesn’t regenerate, and its ability to pump invariably declines with age,” says Anthony Cammarato, Ph.D., co-principal investigator on the study and an assistant professor of medicine and physiology at the Johns Hopkins University School of Medicine.

“Our findings reveal that vinculin fuels beneficial structural and physiologic changes in aging heart cells, and it can be an important therapeutic target to slow down the heart muscle’s inevitable demise,” Cammarato adds.

Jennifer Van Eyk, Ph.D., of Johns Hopkins was a co-investigator on the study.

Other institutions involved in the research included San Diego State University, Cedars-Sinai Medical Center, the National Institute on Aging and the Sanford-Burnham Medical Research Institute in La Jolla, California.

The work was funded by the National Institutes of Health, the American Heart Association and the American Federation for Aging Research.


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