Anti-Inflammatory Klotho Protein Serum Concentration Correlates with Interferon Gamma Expression Related to the Cellular Activity of Both NKT-like and T Cells in the Process of Human Aging

Int J Mol Sci. 2023 May 7;24(9):8393. doi: 10.3390/ijms24098393.

Abstract

Klotho is a beta-glucuronidase that reveals both anti-inflammatory and anti-oxidative properties that have been associated with mechanisms of aging. The study aimed to analyze the relationships between the serum concentration of soluble α-Klotho and cellular activity of two populations of lymphocytes; T and NKT-like cells corresponding to the level of cytokine secretion; i.e., IFN-γ, TNF-α, and IL-6. The studied population comprised three age groups: young individuals ('young'), seniors aged under 85 ('old'), and seniors aged over 85 ('oldest'). Both NKT-like and T cells were either non-cultured or cultured for 48 h and stimulated appropriately with IL-2, LPS or PMA with ionomycin to compare with unstimulated control cells. In all studied age groups non-cultured or cultured NKT-like cells revealed higher expressions of TNF-α, IL-6, and IFN-γ than T cells. α-Klotho concentration in serum decreased significantly in the process of aging. Intriguingly, only IFN-γ expression revealed a positive correlation with α-Klotho protein serum concentration in both non-cultured and cultured T and NKT-like cells. Since IFN-γ is engaged in the maintenance of immune homeostasis, the observed relationships may indicate the involvement of α-Klotho and cellular IFN-γ expression in the network of adaptive mechanisms developed during the process of human aging.

Keywords: CD3+ cells; CD3+CD56+ cells; Klotho; NKT-like cells; T cells; aging; immune homeostasis; interferon gamma; interleukin 6; tumor necrosis factor.

MeSH terms

  • Aged
  • Aging
  • Anti-Inflammatory Agents / pharmacology
  • Cells, Cultured
  • Humans
  • Interferon-gamma* / metabolism
  • Interleukin-6
  • Klotho Proteins / metabolism
  • T-Lymphocytes*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Interferon-gamma
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Klotho Proteins