Two research groups in the US were able to prevent aging by repairing the DNA of mice.
“There is new research now showing that the aging process can be reversed,” said Johns Hopkins health policy expert Dr. Marty Macari said in “Varney & Co.” Tuesday. “That is, the body may carry a copy of a gene in your body that codes for a younger response to everything physiologically.”
In a recent study published in Cell on January 12, Harvard scientists showed that they can manipulate and reverse the aging process in mice by generating DNA repairs.
The results of a 13-year international study show for the first time that breakdown of epigenetic information accelerates aging in mice and that repairing the epigenome reverses signs of aging.
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“For the past 50 years, popular theory has held that the aging process is caused in large part by the accumulation of mutations. However, there is growing evidence that aging has a significant epigenetic component. That is, the process of DNA or gene amplification that is turned on and off,” said the paper’s senior author of Genetics at the Blavatnik Institute at Harvard Medical School. said David Sinclair, professor and co-director of the Paul F. Glenn Center for the Biology of Aging Research.
“My colleagues and I believe that epigenetic changes are the primary cause of aging, but that these changes are driven by the ongoing process of DNA breakage and repair,” he continued.
“We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals,” Sinclair said.
The Harvard researchers said they wanted to test their findings on larger mammals and eventually people.
“First, the results need to be replicated in larger mammals and humans. Studies in nonhuman primates are currently underway,” Harvard said in a statement.
“We think these results are a turning point in our ability to control aging,” Sinclair said. “This is the first study to show that we can have precise control over the biological age of complex animals; we can drive it forward and backward at will.
More from Harvard:
The team used a recent tool developed by Sinclair’s lab to measure how old the mice were not chronologically, in days or months, but “biologically” based on how many sites across the genome had lost the methyl groups normally attached to them. Compared to untreated mice born at the same time, ICE mice aged significantly longer.
Next, the researchers gave the mice gene therapy that reversed the epigenetic changes they were causing.
“It’s like rebooting a malfunctioning computer,” Sinclair said.
The treatment delivered three genes — Oct4, Sox2, and Klf4, together named OSK — that are activated in stem cells and help rewind mature cells to an earlier state. (Sinclair’s lab used this cocktail to restore vision in blind mice in 2020.)
Organs and tissues of ICE mice resumed a youthful state.
The treatment “set an epigenetic program in motion that caused cells to restore epigenetic information from when they were young,” Sinclair said. “It’s a permanent reset.”
It is not clear how exactly OSK treatment is achieved.
At this point, Sinclair says, the discovery supports the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software that, when accessed, allows an aging, epigenetically scrambled cell to reboot into a youthful, healthy state.
For now, extensive experiments have led the team to conclude that “by manipulating the epigenome, aging can be driven forward and backward,” Yang said.
The video below discusses the effects of DNA breakage and repair:
The second study was conducted by Rejuvenate Bio, a San Diego-based company.
The study, titled “Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice,” was bioRxiv earlier this month.
San Diego-based company Rejuvenate Bio infected aged (124-week-old) mice with adeno-associated viruses (AAVs) carrying genes for three factors, collectively known as OSK.
These animals lived an average of 18 weeks, compared with 9 weeks for the control group, the company reported in a preprint on bioRxiv this month. They partially recovered the DNA methylation patterns of epigenetic marks characteristic of younger animals. Although some studies have suggested that Yamanaka factors may promote cancer, Noah Davidson, chief scientific officer and co-founder of Rejuvenate, says the company has so far found no clear negative effects in mice given the gene therapy.
“I would say it’s provocative—maybe a breakthrough,” says Steven Astad of the University of Alabama at Birmingham, who studies the biology of aging. “But we need to replicate it and explore the mechanism before we can say for sure.”