DJ-1 depletion prevents immunoaging in T-cell compartments

EMBO Rep. 2022 Feb 3;23(3):e53302. doi: 10.15252/embr.202153302. Epub 2022 Jan 17.


Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson's disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

Keywords: CD8 T cells; PARK7/DJ-1; aging; immune aging; immunosenescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Animals
  • Humans
  • Mice
  • Mice, Knockout
  • Oxidative Stress* / genetics
  • Parkinson Disease* / genetics
  • Protein Deglycase DJ-1 / genetics
  • Protein Deglycase DJ-1 / metabolism
  • T-Lymphocytes


  • Protein Deglycase DJ-1