By Pesach Benson and Omer Novoselsky • April 16, 2026
Jerusalem, 16 April, 2026 (TPS-IL) — Scientists have uncovered a surprising mechanism behind some of the most severe forms of rapid aging, showing that the body’s own immune response — rather than DNA damage itself — may be a key driver of tissue degeneration, a discovery that could open new therapeutic pathways.
The study, led by scientists at Hebrew University and published in Genes & Development, focuses on rare genetic conditions such as Ataxia-Telangiectasia and Bloom syndrome. These disorders impair the body’s ability to repair everyday DNA damage, leading to premature aging, neurological decline and elevated cancer risk.
For decades, scientists attributed this deterioration primarily to the accumulation of unrepaired DNA. The new research shifts that view, highlighting the role of a chronic immune response triggered by DNA fragments that leak into cells.
“While it was known that both unrepaired DNA damage and innate inflammatory response contribute to pathology in related syndromes, DNA mutations and cell death took the front stage historically. We discovered that the relative contribution of the activated immune response is much greater than originally thought,” Prof. Itamar Harel and Dr. Marva Bergman told The Press Service of Israel. Harel and Bergman were the study’s co-leaders.
“When DNA repair fails, fragments of DNA leak into the cell’s cytosol,” they said. “The immune system’s sensor, cGAS, mistakes these fragments for a viral infection and triggers a chronic, ‘sterile’ inflammatory response. This response, intended to defend against infection, instead fuels ongoing tissue damage,” they explained.
To test whether this pathway could be modified, the researchers used a fast-aging vertebrate model known as the killifish. Rather than correcting the underlying genetic defects, they reduced cGAS activity.
“We were not convinced ourselves until we saw the data,” Harel and Bergman told TPS-IL. “The ‘smoking gun’ was our ability to reverse the symptoms without actually fixing the underlying genetic mutations.”
Despite persistent DNA damage, the animals showed reduced neuroinflammation, improved tissue integrity and restored reproductive capacity.
“This proved that the body can actually tolerate a surprising amount of DNA damage if we prevent the immune system from overreacting,” Harel and Bergman said.
The study also identified a second role for cGAS: beyond sensing DNA fragments, it can enter the nucleus and interfere with DNA repair, compounding cellular stress. This dual activity helps explain how the pathway accelerates degeneration once activated.
The scientists stressed that cGAS is essential for antiviral defense, making any therapeutic approach a matter of balance rather than suppression.
“This is a critical balance,” they said. “We aren’t proposing a total ‘shut-off’ of the immune system. Instead, we envision ‘precision modulation.’”
The most immediate potential applications lie in rare DNA repair disorders, where targeting the cGAS pathway could offer a new therapeutic avenue. As the researchers told TPS-IL, “It could lead to the identification of cGAS and its downstream signals as drug targets for ameliorating the phenotypes of DNA repair disorders.”
Beyond treatment, the findings may also help refine disease monitoring. Measuring activity in the cGAS pathway could provide a biomarker for tracking progression and response to therapy. More broadly, the work points toward emerging “geroprotection” strategies — interventions aimed at reducing inflammation-driven tissue damage across multiple age-related conditions.
While still at an early stage and largely based on animal models, the findings suggest a broader biological principle: aging-related decline may be driven not only by accumulated damage, but by how the body responds to it.
Looking ahead, the team plans to further dissect cGAS’s distinct roles in immunity and DNA repair in order to identify safer ways to tune the pathway.
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