A new study published in Nature Communications by Prof. Haim Cohen and collaborators provides compelling evidence that key features of liver aging are not fixed and can be reversed at the molecular level.

The research demonstrates that enhancing SIRT6 activity restores youthful patterns of chromatin organization in aged liver cells, reversing fundamental epigenetic and structural changes associated with aging. Importantly, these changes are closely linked to two of the most established drivers of biological aging: chronic inflammation and metabolic dysfunction.

By reprogramming age-associated chromatin states, SIRT6 activity is associated with a shift toward reduced inflammatory signaling and improved metabolic regulation, two interconnected hallmarks that strongly influence systemic decline across tissues.

This is particularly significant because chronic low-grade inflammation (“inflammaging”) and metabolic deterioration are among the best-characterized and most powerful accelerators of aging and age-related disease. Their partial reversal at the level of chromatin organization suggests a deeper regulatory reset rather than a surface-level symptomatic effect.

For SirTLab, these findings further validate the biological foundation underlying our therapeutic strategy: targeting SIRT6 to restore cellular resilience and promote healthy tissue function in aging organs, with a primary focus on liver-centered metabolic and systemic aging processes.

This aligns directly with SirTLab’s lead program, SIRT6 mRNA 0.18, an mRNA-LNP therapeutic designed to increase SIRT6 activity specifically in the liver. In preclinical studies, SIRT6 0.18 has demonstrated robust hepatic delivery and sustained elevation of SIRT6 activity, accompanied by improvements in key age-associated functional pathways, including reduced inflammatory signaling, improved lipid handling, and enhanced metabolic regulation.

These effects are highly consistent with the biological framework described in Prof. Cohen’s work, in which SIRT6-mediated restoration of chromatin organization is linked to suppression of inflammatory programs and rebalancing of metabolic state in aged liver tissue. Together, these data strengthen the rationale that SIRT6 is a central regulator of liver aging and a compelling therapeutic target for restoring systemic physiological resilience.

SirTLab continues to advance SIRT6-based therapeutics to translate these mechanistic insights into clinically meaningful interventions that address the root drivers of aging biology.

Link to the paper:

https://www.nature.com/articles/s41467-026-73115-y