Epigenetic Attenuation of Interferon Signaling is Associated With Aging-related Improvements in Systemic Lupus Erythematosus.

Details

• Alternative Title:
  Science Translational Medicine, 2025, v. 17, no. 804: Epigenetic Attenuation of Interferon Signaling is Associated With Aging-related Improvements in Systemic Lupus Erythematosus.
• Journal Article:
  Science Translational Medicine
• Personal Author:
  Narendra, Rithwik ; Van Phan, Hoang ; Patterson, Sarah L. ; Almonte-Loya, Ana ; Lydon, Emily C. ; Lanata, Cristina ; Love, Christina ; Park, Joonsuk ; Shimoda, Michiko ; Barcellos, Lisa ; Mekonen, Honey ; Detweiler, Angela ; Deosthale, Padmini ; Neff, Norma ; Criswell, Lindsey A. ; Maliskova, Lenka ; Eckalbar, Walter ; Fragiadakis, Gabriela K. ; Yazdany, Jinoos ; Dall'Era, Maria ; Katz, Patricia ; Ye, Chun Jimmie ; Sirota, Marina ; Langelier, Charles R.
• Description:
  In the general population, aging is associated with an increase in systemic inflammation and chronic disease burden. However, in systemic lupus erythematosus (SLE), older age is uniquely associated with a decrease in disease activity, suggesting a distinct relationship between aging and inflammation. Using a multiomic approach, we compared aging-related changes in the peripheral blood immune profiles of 287 patients with SLE and 928 healthy controls. In patients with SLE, aging correlated with lower expression of interferon (IFN)-stimulated genes (ISGs) across multiple cell types, decreased plasma IFN-α2, and differential genome methylation. Both patients with SLE and controls demonstrated age-related declines in naïve T cells, but only patients with SLE exhibited increases in CD56
  
  natural killer cells with older age. Of the genes both down-regulated and hypermethylated with older age, ISGs were disproportionately represented, suggesting a role for epigenetic silencing. Altogether, we found that patients with SLE exhibit unique aging-related decreases in IFN signaling that correlate with improved disease activity.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Lupus Erythematosus, Systemic
  • Aging
  • Signal Transduction
  • Epigenesis, Genetic
  • Middle Aged
  • Female
  • Interferons
  • Adult
  • DNA Methylation
  More +
• Source:
  Science Translational Medicine, 2025, v. 17, no. 804
• DOI:
  https://doi.org/10.1126/scitranslmed.adt5550
• ISSN:
  1946-6234 ; 1946-6242
• Pubmed ID:
  40561001
• Pubmed Central ID:
  PMC13012812
• Document Type:
  Text
• Funding:
  T32 AI007641/AI/NIAID NIH HHSUnited States/ ; U01 DP005120/DP/NCCDPHP CDC HHSUnited States/ ; U01 DP006701/DP/NCCDPHP CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  eadt5550 (27 pdf pages)
• Volume:
  17
• Issue:
  804
• Download URL:
  https://stacks.cdc.gov/view/cdc/261304/cdc_261304_DS1.pdf
• File Type:
  [PDF - 1.52 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:b5735045d62a1416bcd3e419d0a50800b96e34612e628bbdca2d77021fc265b2e954ed58caf86c2dbcf9a8082fe9c9c4d870054249ad05a2bc53f138a06964bc