Vinculin Upregulation Improves Cardiovascular Health and Extends Life in Flies

Researchers here report on a single gene alteration in fruit flies, increased levels of vinculin, that improves cardiovascular function in later life and increases life span. Effect sizes in flies are much larger than those in humans, where is is possible to directly compare interventions. Short-lived species have evolved to exhibit a far greater plasticity of longevity in response to environmental and genetic changes, at least in those methodologies tested to date. It remains to be seen as to whether the initial hypothesis on the important mechanisms linking vinculin levels to improved health turn out to be correct. Vinculin is involved in common cellular processes that in turn influence many aspects of tissue function. This is frequently the case in studies of slowed aging - finding out exactly how and why it works is a long and arduous process.

Our cells tend to lose their shape as we grow older, contributing to many of the effects we experience as aging. This poses particular problems for the heart, where aging can disrupt the protein network within muscle cells that move blood around the body. Researchers discovered that maintaining high levels of the protein vinculin - which sticks heart muscle cells to one another - confers health benefits to fruit flies. Their work shows that fruit flies bred to produce 50 percent more vinculin enjoyed better cardiovascular health and lived a third of their average life span longer.

Vinculin works at the intercalated disks that glue together heart muscle cells, called cardiomyocytes. As we age, cardiomyocytes make less vinculin. Vinculin organizes the heart's contractile proteins, so as vinculin levels fall our heartbeats become disorganized and less efficient. By breeding flies with complementary genes, researchers created a genetic switch that turned on extra copies of the vinculin-coding gene. To ensure that only cardiomyocytes were producing the protein, the group used the same activation machinery as a heart development gene called Tinman.

While typical fruit flies live for roughly six weeks, flies that made more vinculin survived up to nine weeks. Additionally, flies with a vinculin boost were more active and able to climb the walls of their enclosures, a test of fruit fly athletic ability. Researchers were surprised how much improving cardiac function also helped the flies maintain a healthier metabolism. To measure this improvement, researchers fed the flies a special form of glucose and detected how the flies modified and used the sugar. Flies with more vinculin broke down more glucose than their counterparts. The team concluded higher vinculin levels in the flies' hearts enabled other organs to efficiently get the nutrients they needed in the breakdown process.



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