Scientists could be a big step closer to reversing aging with the discovery of a “smoking gun” chemical trigger for aging that can be retooled with gene editing techniques. You can’t go buy a magic fountain-of-youth pill tomorrow, but the finding reported this week by Salk Institute researchers could have far-reaching implications for human longevity.
It’s not science fiction to think that within a couple of decades, practical age-reversing treatments may be available, according to Juan Carlos Izpisua Belmonte, a senior author of the research paper. He and fellow Salk Institute scientists (collaborating with researchers at the Chinese Academy of Sciences) made their breakthrough while studying Werner syndrome, a rare genetic disorder that causes rapid aging. Using human stem cells, they found that the gene mutation tied to Werner syndrome causes disorganization of heterochromatin, the tightly packed DNA “bundles” found in a cell’s nucleus.
On the outside of these heterochromatin bundles are chemical tags known as epigenetic marks, which control – and can change – the architecture of the heterochromatin, Scientists have discovered that these epigenetic marks can act like switches, causing genes to be turned on or off. That process goes haywire in people who have Werner syndrome, resulting in accelerated aging. “This disruption of normal DNA packaging is a key driver of aging,”says Izpisua Belmonte.
Scientists are now working on techniques that will enable the culprit epigenetic marks to be manipulated. “If we are artificially able to play around with these marks, we may be able to alter the process of aging,” Izpisua Belmonte said in an interview. “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.”
Until now, scientists researching aging have focused mainly on mutations in the DNA itself that may cause a deceleration of the aging process. The discovery that telomeres, caps at the end of chromosomes that protect them from damage but shorten as one gets older, seem to be augmented by resveratrol (a grape skin extract) sent consumers rushing to buy supplements containing the magical ingredient. Cannabidiol (CBD) is another powerful antioxidant connected to aging reversal, specifically in the brain – reversing cognitive decline and treating neurodegenerative disorders.
The discovery of the epigenetic marks that trigger aging opens up a whole new area of research that could produce treatments for age-related illnesses as well as making our cells more youthful. Epigenetics is a field of biology that examines how genes change as a result of environmental factors in ways that can be passed onto the next generation, and how such changes can affect disease. Unlike genes, a person’s epigenetics are affected by external factors like stress and exercise. There is a lively debate in the scientific and psychological communities about whether an ancestor’s severe emotional trauma can become hereditary – not just as an emotional profile, but as a result of the epigenetic changes it causes. Studies on the children and grandchildren of Holocaust survivors may support this contention.
Neurobiologist Isabelle Mansuy of the University of Zurich identified the descendents of Holocaust survivors as one of the best epigenetics study groups available for because their parents’ trauma was so great, their population is so well known, and there are now multiple generations to study. Mansuy published a study in the journal Biological Psychiatry using mice as stand-ins for first-generation Holocaust survivors.
Genetic changes were triggered in a control group of male mice as a result of trauma – essentially they had PTSD and it impacted their genes as well as their psychology. These sad mice fathered offspring which were then raised by happy mothers with none of the trauma and separation the fathers had suffered. Yet when they grew up, not only did the off-spring exhibit the same anxious behavior as their fathers; they also had the same signature gene changes. “We saw the genetic differences both in the brains of the offspring mice and in the germline — or sperm — of the fathers,” said Mansuy, whose work is ongoing.
The Salk research adds to the good news about epigeneticists have been telling us – that we have more control than we might think over our own genes and the time is approaching when we will be able to “override” or adjust our own molecular biology.