| First Author | Ding C | Year | 2023 |
| Journal | Nat Aging | Volume | 3 |
| Issue | 7 | Pages | 813-828 |
| PubMed ID | 37277640 | Mgi Jnum | J:342907 |
| Mgi Id | MGI:7543732 | Doi | 10.1038/s43587-023-00428-8 |
| Citation | Ding C, et al. (2023) A T(reg)-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver. Nat Aging 3(7):813-828 |
| abstractText | Regulatory T (T(reg)) cells modulate several aging-related liver diseases. However, the molecular mechanisms regulating T(reg) function in this context are unknown. Here we identified a long noncoding RNA, Altre (aging liver T(reg)-expressed non-protein-coding RNA), which was specifically expressed in the nucleus of T(reg) cells and increased with aging. T(reg)-specific deletion of Altre did not affect T(reg) homeostasis and function in young mice but caused T(reg) metabolic dysfunction, inflammatory liver microenvironment, liver fibrosis and liver cancer in aged mice. Depletion of Altre reduced T(reg) mitochondrial integrity and respiratory capacity, and induced reactive oxygen species accumulation, thus increasing intrahepatic T(reg) apoptosis in aged mice. Moreover, lipidomic analysis identified a specific lipid species driving T(reg) aging and apoptosis in the aging liver microenvironment. Mechanistically, Altre interacts with Yin Yang 1 to orchestrate its occupation on chromatin, thereby regulating the expression of a group of mitochondrial genes, and maintaining optimal mitochondrial function and T(reg) fitness in the liver of aged mice. In conclusion, the T(reg)-specific nuclear long noncoding RNA Altre maintains the immune-metabolic homeostasis of the aged liver through Yin Yang 1-regulated optimal mitochondrial function and the T(reg)-sustained liver immune microenvironment. Thus, Altre is a potential therapeutic target for the treatment of liver diseases affecting older adults. |
