Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

A hallmark of CNS aging is sterile, chronic, low-grade neuroinflammation. Understanding how the develops chronic inflammation necessary to achieve extended healthspan. Characterisation neuroinflammatory molecular triggers remains limited. Interventions that reduce neuroinflammation and extend health lifespan could be useful in this regard. One such intervention intermittent fasting (IF), but IF impacts insufficiently understood. To address this, we performed deep RNA-sequencing on young, middle-aged, old, mouse regions. Additionally, sequenced spinal cord animals subject adult lifelong IF. We found most differentially expressed genes (DEGs) at middle age were region specific (~ 50–84%), whilst effect weakened 18–72%) old age, suggesting emergence a more general global profile. DEGs from all regions enriched for inflammatory immune ontologies. Surprisingly, SC was aging- neuroinflammation-impacted both ages, with by far highest number DEGs, largest net increase expression transposable elements (TEs), greatest enrichment immune-related ontologies, generally larger increases gene expression. Overall, normal upregulation sensors non-self, DNA/RNA, activation inflammasomes, cGAS-STING1 interferon response genes, across CNS. Whilst still developed an profile SC, average lower ~ 50% compared age-matched controls. IF-specific apparent, also acts separate, potentially targetable, pathways those impacted aging. Expression disease associated microglia, phagocytic exhaustion, STING1, inflammasome decreased Significantly, TE reversed decrease. In summary, find hotspot, attenuates neuroinflammaging rebalancing transposonome.

Language: Английский