Lamtor5 Loss Drives Macrophage Senescence and Systemic Aging via cGAS in Mice
Updated
Updated · Nature.com · Jul 16
Lamtor5 Loss Drives Macrophage Senescence and Systemic Aging via cGAS in Mice
1 articles · Updated · Nature.com · Jul 16
Summary
Mouse experiments identified Lamtor5 as an age-linked regulator whose loss in myeloid cells pushed macrophages into senescence and triggered tissue damage and broader aging features.
Mechanistically, Lamtor5 bound cGAS and promoted its ESCRT-dependent degradation; when Lamtor5 declined with age, cGAS-driven inflammatory signaling rose and spread aging-related dysfunction.
Transferring senescent Lamtor5-deficient macrophages accelerated aging in young mice, while transplanting young macrophages or clearing senescent cells eased aging signs in Lamtor5 conditional knockout mice.
Two interventions also reversed phenotypes in aged mice: macrophage-targeted cGAS siRNA and a small peptide blocking the Lamtor5-cGAS interface, pointing to macrophage-based anti-aging therapies.
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Targeting Lamtor5/cGAS Axis to Combat Inflammaging: Breakthroughs in Macrophage Senescence and Age-Related Disease
Overview
A groundbreaking 2026 study revealed that Lamtor5 is a key regulator of macrophage senescence and systemic aging. Researchers found that Lamtor5 levels decline with age in both mice and humans, and this reduction directly contributes to aging features. When Lamtor5 was specifically deleted in mouse immune cells, the animals showed clear signs of premature aging, including increased senescence markers, DNA damage, and inflammation. The study uncovered that Lamtor5 normally restrains harmful inflammatory signaling by promoting cGAS degradation. These findings highlight Lamtor5’s central role in controlling inflammation and aging, and suggest it could be a promising target for future anti-aging therapies.