Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching

Nat Aging. 2022 Mar;2(3):231-242. doi: 10.1038/s43587-022-00187-y. Epub 2022 Mar 18.


Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell immunity. Here we show that branching increases with age in females more than males, in naïve more than memory T cells, and in CD4+ more than CD8+ T cells. Female sex hormones and thymic output of naïve T cells (TN) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse TN cells, and triggered increased branching. N-acetylglucosamine, a rate-limiting metabolite for branching, increased with age in humans and synergized with IL-7 to raise branching. Reversing elevated branching rejuvenated T cell function and reduced severity of Salmonella infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through TN maintenance but inhibits TN function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.

Keywords: Immunosenescence; N-acetyglucosamine; N-glycan branching; N-glycosylation; T cell, infection; aging; immunity; interleukin-7.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine*
  • Aging
  • Animals
  • CD8-Positive T-Lymphocytes*
  • Female
  • Humans
  • Interleukin-7
  • Male
  • Mice
  • Polysaccharides


  • Acetylglucosamine
  • Interleukin-7
  • Polysaccharides