Deficient mitochondrial biogenesis in IL-2 activated NK cells correlates with impaired PGC1-α upregulation in elderly humans

Dante Miranda, Claudia Jara, Sophia Mejias, Viviana Ahumada, Jorge Ibañez, Sandra Hirsch, Margarita Montoya, Marcelo A Cortez San Martin

Research output: Contribution to journalArticle

Abstract

Immunosenescence has been described as age-associated changes in the immune function which are thought to be responsible for the increased morbidity with age. Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in immune defense against tumor and microbial diseases. Interestingly, aging-related NK cell dysfunction is associated with features of aging such as tumor incidence, reduced vaccination efficacy, and short survival due to infection. It is known that NK cell effector functions are critically dependent on cytokines and metabolic activity. Our aim was to determine whether there is a difference in purified human NK cell function in response to high concentration of IL-2 between young and elder donors. Here, we report that the stimulation of human NK cells with IL-2 (2000 U/mL) enhance NK cell cytotoxic activity from both young and elderly donors. However, while NK cells from young people responded to IL-2 signaling by increasing mitochondrial mass and mitochondrial membrane potential, no increase in these mitochondrial functional parameters was seen in purified NK cells from elderly subjects. Moreover, as purified NK cells from the young exhibited an almost three-fold increase in PGC-1α expression after IL-2 (2000 U/mL) stimulation, PGC-1α expression was inhibited in purified NK cells from elders. Furthermore, this response upon PGC-1α expression after IL-2 stimulation promoted an increase in ROS production in NK cells from elderly humans, while no increase in ROS production was observed in NK cells of young donors. Our data show that IL-2 stimulates NK cell effector function through a signaling pathway which involves a PGC-1α-dependent mitochondrial function in young NK cells, however it seems that NK cells from older donors exhibit an altered IL-2 signaling which affects mitochondrial function associated with an increased production of ROS which could represent a feature of NK cell senescence.

LanguageEnglish
Pages73-78
Number of pages6
JournalExperimental Gerontology
Volume110
DOIs
Publication statusPublished - 1 Sep 2018

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Organelle Biogenesis
Natural Killer Cells
Interleukin-2
Up-Regulation
Tumors
Aging of materials
Tissue Donors
Lymphocytes
Cytokines
Membranes
Mitochondrial Membrane Potential
Cell Aging
Lymphocyte Subsets

Keywords

  • Immunosenescence
  • Interleukin-2
  • Mitochondria
  • NK cells
  • PGC-1α

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Deficient mitochondrial biogenesis in IL-2 activated NK cells correlates with impaired PGC1-α upregulation in elderly humans. / Miranda, Dante; Jara, Claudia; Mejias, Sophia; Ahumada, Viviana; Ibañez, Jorge; Hirsch, Sandra; Montoya, Margarita; Cortez San Martin, Marcelo A.

In: Experimental Gerontology, Vol. 110, 01.09.2018, p. 73-78.

Research output: Contribution to journalArticle

Miranda, Dante ; Jara, Claudia ; Mejias, Sophia ; Ahumada, Viviana ; Ibañez, Jorge ; Hirsch, Sandra ; Montoya, Margarita ; Cortez San Martin, Marcelo A. / Deficient mitochondrial biogenesis in IL-2 activated NK cells correlates with impaired PGC1-α upregulation in elderly humans. In: Experimental Gerontology. 2018 ; Vol. 110. pp. 73-78.
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