Spermine and spermidine modulate T-cell function in older adults with and without cognitive decline ex vivo

Aging (Albany NY). 2020 Jun 30;12(13):13716-13739. doi: 10.18632/aging.103527. Epub 2020 Jun 30.

Abstract

The global increase in neurodegenerative disorders is one of the most crucial public health issues. Oral polyamine intake was shown to improve memory performance which is thought to be mediated at least in part via increased autophagy induced in brain cells. In Alzheimer's Disease, T-cells were identified as important mediators of disease pathology. Since autophagy is a central regulator of cell activation and cytokine production, we investigated the influence of polyamines on T-cell activation, autophagy, and the release of Th1/Th2 cytokines from blood samples of patients (n=22) with cognitive impairment or dementia in comparison to healthy controls (n=12) ex vivo. We found that spermine downregulated all investigated cytokines in a dose-dependent manner. Spermidine led to an upregulation of some cytokines for lower dosages, while high dosages downregulated all cytokines apart from upregulated IL-17A. Autophagy and T-cell activation increased in a dose-dependent manner by incubation with either polyamine. Although effects in patients were seen in lower concentrations, alterations were similar to controls.We provide novel evidence that supplementation of polyamines alters the function of T-cells. Given their important role in dementia, these data indicate a possible mechanism by which polyamines would help to prevent structural and cognitive decline in aging.

Keywords: T cell; cytokines; dementia; spermidine; spermine.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology
  • Autophagy / drug effects
  • Autophagy / immunology
  • Case-Control Studies
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / immunology
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / prevention & control*
  • Cytokines / analysis
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dementia / blood
  • Dementia / immunology
  • Dementia / physiopathology
  • Dementia / prevention & control*
  • Dietary Supplements*
  • Down-Regulation
  • Female
  • Healthy Volunteers
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Spermidine / administration & dosage*
  • Spermine / administration & dosage*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • Spermine
  • Spermidine