Other
15 Authors
- Bennett DA,
- Liu X,
- Yankner BA,
- Liu P,
- Qadota H,
- Drake D,
- Wang ZH,
- Xia Y,
- Ye KX,
- Berglund K,
- Ye K,
- Yu SP,
- Wang XC,
- Matheny CJ,
- Benian GM
| First Author | Xia Y | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 13 | Pages | eabj8658 |
| PubMed ID | 35353567 | Mgi Jnum | J:338291 |
| Mgi Id | MGI:7262297 | Doi | 10.1126/sciadv.abj8658 |
| Citation | Xia Y, et al. (2022) Neuronal C/EBPbeta/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression. Sci Adv 8(13):eabj8658 |
| abstractText | The age-related cognitive decline of normal aging is exacerbated in neurodegenerative diseases including Alzheimer's disease (AD). However, it remains unclear whether age-related cognitive regulators in AD pathologies contribute to life span. Here, we show that C/EBPbeta, an Abeta and inflammatory cytokine-activated transcription factor that promotes AD pathologies via activating asparagine endopeptidase (AEP), mediates longevity in a gene dose-dependent manner in neuronal C/EBPbeta transgenic mice. C/EBPbeta selectively triggers inhibitory GABAnergic neuronal degeneration by repressing FOXOs and up-regulating AEP, leading to aberrant neural excitation and cognitive dysfunction. Overexpression of CEBP-2 or LGMN-1 (AEP) in Caenorhabditis elegans neurons but not muscle stimulates neural excitation and shortens life span. CEBP-2 or LGMN-1 reduces daf-2 mutant-elongated life span and diminishes daf-16-induced longevity. C/EBPbeta and AEP are lower in humans with extended longevity and inversely correlated with REST/FOXO1. These findings demonstrate a conserved mechanism of aging that couples pathological cognitive decline to life span by the neuronal C/EBPbeta/AEP pathway. |
