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LEF1 isoforms regulate cellular senescence and aging.

Minxue Jia1,2, Khaled Sayed1,3, Maria G Kapetanaki1,4

  • 1Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Aging Cell
|November 14, 2023
PubMed
Summary
This summary is machine-generated.

Lymphoid enhancer binding factor 1 (LEF1) is identified as a key regulator of lung aging and cellular senescence. Differential LEF1 isoform expression is crucial for senescence, impacting age-related lung diseases.

Keywords:
IPFLEF1agingcellular senescencelung

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Area of Science:

  • Gerontology
  • Molecular Biology
  • Immunology

Background:

  • Cellular senescence is a key mechanism in aging and age-related diseases.
  • High-throughput data and analysis algorithms aid in identifying disease-driving pathways.
  • Understanding lung aging requires examining transcriptional regulation in immune cells.

Purpose of the Study:

  • To identify key regulators of lung aging.
  • To analyze age-related transcriptional changes in human and mouse lung immune cells.
  • To investigate the role of lymphoid enhancer binding factor 1 (LEF1) in aging and senescence.

Main Methods:

  • Comparative analysis of transcriptional profiles from aged and young human and mouse lung immune cells (macrophages, T cells, B cells).
  • Validation in cell culture assays and human lung samples.
  • Examination of LEF1 isoform expression and its role in cellular senescence.
  • Analysis of LEF1 in lung tissue from idiopathic pulmonary fibrosis patients.

Main Results:

  • Lymphoid enhancer binding factor 1 (LEF1) was identified as an age-associated gene expression regulator across multiple cell types, tissues, and species.
  • Differential expression of long and short LEF1 isoforms was found to be a critical regulatory mechanism in cellular senescence.
  • LEF1 showed significant dysregulation in lung tissue from patients with idiopathic pulmonary fibrosis, an age-related disease linked to senescence.

Conclusions:

  • LEF1 is a significant factor in the aging process.
  • The differential regulation of LEF1 isoforms is associated with cellular senescence in both humans and mice.
  • LEF1 dysregulation is linked to age-related lung pathologies like idiopathic pulmonary fibrosis.