What Causes Humans to Age: New Finding May Combat Age-Related Diseases

Scientists may have discovered what causes humans to age, which could lead to methods of preventing and treating age-related diseases. They've discovered that tightly packaged bundles of cellular DNA deteriorate during the aging process.

"Our findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging," said Juan Carlos Izpisua Belmonte, senior author of the new study, in a news release. "This has implications beyond Werner syndrome, as it identifies a central mechanism of aging-heterochromatin disorganization-which has been shown to be reversible."

Werner syndrome is a genetic disorder that causes people to age more rapidly than normal. It affects about one in every 200,000 people in the United States, and people with the disorder suffer age-related diseases early in life.

This disease is caused by a mutation to the Werner syndrome RecQ helicase-like gene, known as the WRN gene for short, which generates the WRN protein. When the protein is mutated in Werner syndrome, it disrupts the replication and repair of DNA and the expression of genes.

In order to examine this phenomenon a bit more closely, the scientists created a cellular model of Werner syndrome by using gene-editing technology to delete WRN gene in human stem cells. The stem cell model of the disease gave the scientists the ability to study the rapidly aging cells in the lab.

The researchers found that the deletion of the WRN gene led to disruptions to the structure of heterochromatin, the tightly packed DNA found in the cell's nucleus. This DNA bundle acts as a switchboard for controlling genes' activity; it also directs a cell's molecular machinery.

"Our study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation," said Izpisua Belmonte. "More broadly, it suggests that accumulated alterations in the structure of heterochromatin may be a major underlying cause of cellular aging. This begs the question of whether we can reverse these alterations-like remodeling an old house or care-to prevent, or even reverse, age-related declines and diseases."

The findings are published in the journal Science.

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