There are many among us who believe that time is a predator, patiently waiting for our bodies to age and yield toward its inevitable fate. However, there are few within the sciences that look at the ageing process through a different lens—viewing it as a disease, one that can be treated, slowed, and possibly even reversed.
Scientists from the Salk Institute and the Chinese Academy of Science have published new data that they believe identifies a key driver in the aging process. The researchers found that the genetic mutations associated with Werner syndrome, a disorder that leads to premature aging and death is triggered by the deterioration of DNA bundles known as heterochromatin. A greater understanding of this process could lead to the treatment and prevention of age-related disorders such as Alzheimer’s, diabetes, and even cancer.
“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,” explained Juan Carlos Izpisua Belmonte, Ph.D., professor in the gene expression laboratory at the Salk Institute and senior author on the paper. “This has implications beyond Werner syndrome, as it identifies a central mechanism of aging—heterochromatin disorganization—which has been shown to be reversible.”
The findings from this study were published recently in Science through an article entitled “A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.”
Werner syndrome (WS), also known as adult progeria, is a genetic disorder that causes rapid aging and recapitulates certain aspects of the human physiological aging process. The disease is caused by a mutation within the Werner syndrome, RecQ helicase like gene (WRN). This enzyme typically helps maintain genomic stability and integrity, however in WS, the mutant protein disrupts DNA replication, repair, and gene expression.
Dr. Izpisua Belmonte and his colleagues sought to determine how mutated WRN could wreak so much havoc on cellular process. To that end, the researchers generated an in vitro model of WS employing human embryonic stem cells that contained a genetic deletion of the WRN gene.
The investigators observed that the altered stem cells recapitulated the WS phenotype and began to age more rapidly. At the molecular level they found that the deletion of WRN led to disruptions within the structure of heterochromatin, a scenario that could lead to global gene expression changes through epigenetic regulation.
“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,” stated Dr. 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 car—to prevent, or even reverse, age-related declines and diseases.”
While their results are exciting and could have a major impact for age-related disease research, Dr. Izpisua Belmonte expressed caution in over interpreting the results, as more extensive studies will be required to fully understand the relationship between heterochromatin disorganization and aging.