Transcriptome analysis of the effect of Armh4 on aging

Aging is an inevitable process integrating chronological alterations of multiple organs. A growing aging population necessitates feasible anti-aging strategies to deal with age-associated health problems. We previously performed a proteomics analysis in a healthy-aging cohort, and revealed an age-related downregulation of ARMH4. Here we generate a whole-body Armh4-knockout mouse line, and investigate its impact on systemic aging. Under normal feeding conditions, Armh4 deficiency significantly lowers spontaneous mortality and extends maximum lifespan. In the female mice, Armh4 deficiency postpones sexual maturity for one week. At the organ level, the age-related pathologies of the heart, liver, kidney, and spleen are substantially alleviated by Armh4 deletion. Mechanistically, ARMH4 interacts with IGF1R/FGFR1 to sensitize the activation of PI3K-Akt-mTORC1 and Ras-MEK-ERK pathways, consequently promoting protein synthesis and inhibiting autophagy. Moreover, ARMH4 is required for the maintenance of IGF1R/FGFR1 expressions through regulating the transcription factor c-Myc. Therefore, ARMH4 maintains a positive-feedback growth signaling to promote aging. Overall design: Normal and healthy c57bl/6j young mice and systemic Armh4 gene knockout mice were raised in a stable environment (room temperature 24±3?; indoor humidity 55±5%), 12-hour light/12-hour dark cycle, fed normal food, and raised to 25 months of age, and divided into WT_Aged group and KO_Aged group. In addition, the feeding environment of WT_Young group and KO_Young group mice was consistent with that of aged mice, and they were raised for 8 weeks, with at least 6 mice in each group. Mice were anesthetized with inhaled anesthetics and killed by cervical dislocation. The heart was immediately dissected and stored at -80°C. Select 4 independent biological replicate samples from each of the four separate groups, namely WT_Aged, KO_Aged, WT_Young, and KO_Young, to extract RNA. RNA-seq was provided by Beijing Genomics Institute (BGI)