Age-driven loss of Lamtor5, a key lysosomal mTOR activation complex subunit, causes macrophage immunosenescence and systemic aging by unleashing cGAS-STING paracrine inflammation; Lamtor5 restoration in aged mice reverses these phenotypes.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse |
| Journal | Cell Death and Differentiation |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1038/s41418-026-01823-5 · PMID 42463581 |
Lamtor5 (late endosomal/lysosomal adapter, MAPK and mTOR activator 5) was identified as an age-dependent factor controlling innate immune cell function. Age-associated Lamtor5 decline impairs mTOR-dependent macrophage signaling, triggering cGAS-mediated paracrine inflammatory senescence. Restoring Lamtor5 in aged mice rescued immunosenescence and attenuated systemic aging phenotypes.
| Intervention | Lamtor5 overexpression / restoration |
| Target | Lamtor5 / mTORC1 Ragulator complex / cGAS-STING |
| Model | Mouse |
| Effect | Decline of Lamtor5 reduces mTOR activity in aging macrophages, promoting immunosenescence; Lamtor5 restoration reverses aging phenotypes |