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A T

Chenbo Ding1,2, Zhibin Yu1,2, Esen Sefik3,4

  • 1Medical Center on Aging, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Nature Aging
|June 5, 2023
PubMed
Summary
This summary is machine-generated.

A novel long noncoding RNA, Altre, maintains liver health in aging mice by regulating regulatory T cell (Treg) mitochondrial function. Its depletion accelerates Treg aging and liver disease progression, highlighting Altre as a therapeutic target.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Aging Research

Background:

  • Regulatory T (Treg) cells are crucial in managing aging-related liver diseases.
  • The precise molecular mechanisms governing Treg function during aging remain largely unelucidated.

Purpose of the Study:

  • To identify molecular regulators of Treg function in the aging liver.
  • To investigate the role of the long noncoding RNA Altre in Treg aging and liver disease pathogenesis.

Main Methods:

  • Treg-specific gene deletion in mouse models.
  • Mitochondrial function assays (respiratory capacity, integrity).
  • Reactive oxygen species (ROS) measurements and apoptosis assays.
  • Lipidomic analysis.
  • Chromatin immunoprecipitation and gene expression analysis.

Main Results:

  • Altre, a nuclear-localized lncRNA, increases with age in liver Tregs.
  • Treg-specific Altre deletion in aged mice leads to metabolic dysfunction, inflammation, fibrosis, and cancer.
  • Altre depletion impairs Treg mitochondrial function, increases ROS, and promotes apoptosis.
  • Altre interacts with Yin Yang 1 to regulate mitochondrial gene expression and Treg fitness.

Conclusions:

  • The lncRNA Altre is essential for maintaining immune-metabolic homeostasis in the aged liver.
  • Altre preserves Treg mitochondrial function and survival via the Yin Yang 1 pathway.
  • Altre represents a promising therapeutic target for age-related liver diseases.