Mechanism behind human ageing revealed
New York: A new research has linked the ageing process to the deterioration of tightly packaged bundles of cellular DNA.
Scientists in the US found that the genetic mutations underlying Werner syndrome – a disorder that leads to premature ageing and death — resulted in the deterioration of bundles of DNA known as heterochromatin.
The discovery could lead to ways of countering age-related physiological declines by preventing or reversing damage to heterochromatin, the researchers aver.
“Our findings show that the gene mutation that causes Werner syndrome results in the disorganisation of heterochromatin, and that this disruption of normal DNA packaging is a key driver of ageing,” said senior study author Juan Carlos Izpisua Belmonte from the California-based Salk Institute for Biological Studies.
“This has implications beyond Werner syndrome, as it identifies a central mechanism of ageing – heterochromatin disorganisation – which has been shown to be reversible,” he added.
Werner syndrome is caused by a mutation to the WRN gene which generates the WRN protein.
Previous studies showed that the normal form of the protein is an enzyme that maintains the structure and integrity of a person’s DNA.
When the protein is mutated in Werner syndrome it disrupts the replication and repair of DNA and the expression of genes, which was thought to cause premature ageing.
However, it was unclear exactly how the mutated WRN protein disrupted these critical cellular processes.
In their study, the Salk scientists created a cellular model of Werner syndrome. The resulting cells mimicked the genetic mutation seen in actual Werner syndrome patients, so the cells began to age more rapidly than normal.
On closer examination, the scientists found that the deletion of the WRN gene also led to disruptions to the structure of heterochromatin, the tightly packed DNA found in a cell’s nucleus.
This bundling of DNA acts as a switchboard for controlling genes’ activity and directs a cell’s complex molecular machinery.
The researchers discovered that deletion of the WRN gene leads to heterochromatin disorganization, pointing to an important role for the WRN protein in maintaining heterochromatin.