Preventing or Reversing Immunosenescence

Can Exercise Be an Immunotherapy?

Adriana L de Araújo; Léia CR Silva; Juliana Ruiz Fernandes; Gil Benard

Immunotherapy. 2013;5(8):879-893.

Innate Immunity & Immunosenescence

Despite the limited number of studies addressing the innate immunity aspects of immunosenescence, some functional and phenotypic aspects do appear altered in the elderly. The functional and phenotypic changes in neutrophils, monocytes/macrophages, dendritic cells (DCs) and NK cells that have been described with aging are summarized in Table 1.^[13–25] Alterations, such as decrease in the antigen presentation capability,^[21] impairment of phagocyte function,^[17] altered cellular signaling^[14] and cytokine release,^[25] likely result in the slowing of the host response to infections and the well-known increased susceptibility to infections of the elderly.

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Table 1. Immunological changes associated with aging in innate immunity.
Cell type	Parameter	Ref.
Neutrophils	Membrane alterations: reduced levels of cholesterol, increased membrane fluidity and dysregulation of receptor recruitment to lipid rafts	[13,14]
	Decreased receptor signaling functions: KPB, JAK, PI3K	[14]
	Preserved or decreased cell number	[15,16]
	Decreased chemotaxis, opsonization, phagocytosis and free radical production	[17]
	Decreased signaling molecules expression: GM-CSF-R, TLR-4, fMLP-R, TREM-1	[18]
	Preserved expression of adhesion molecules: CD11a/CD11c/CD11a/CD18/CD11b/CD18/CD14	[18]
Monocytes/macrophages	Increase in CD16⁺ (proinflammatory) subpopulation	[19]
	Dysregulation of TLR responses (diminished signaling of TLR-1/2)	[20]
	Decreased in antigen presentation: phagocytic ability and free radical production	[21]
DC	Decreased in number (myeloid subpopulation)	[22]
	Decreased in IL-12 production	[22]
	Reduced proportion of pDC expressing TLR-7 or TLR-9	[23]
NK	Decreased function compensated by increased percentage and absolute cell number	[21,24]
	Decreased in CD56^bright (immunoregulatory) subpopulation	[21]
	Increased CD56^dim (cytotoxic) subpopulation	[21]
	Preserved production IFN-γ	[21]
	Decreased in chemokine production	[25]

DC: Dentritic cell; fMLP-R: N-formyl-leucyl-phenylalanine receptor; GM-CSF-R: GM-CSF receptor; pDC: Plasmacytoid dendritic cell; TLR: Toll-like receptor; TREM: Triggering receptor expressed on myeloid cell.

Table 2. Effects of chronic exercise on immunological parameters.
Exercise type	Immunological parameters	Net immune effects	Ref.
Endurance	↑ Lymphocyte proliferation and cytokine production	Positive	[100,101]
	↑ Costimulatory molecules on T lymphocytes	Positive	[102,104]
	↑ DTH	Positive	[103]
	↑ NK cells and phagocytic activity of neutrophils	Positive	[105]
	↑ DCs and maturation	Positive	[106–109]
	↓ Inflammatory background	Positive	[110–114,117]
	Preserved telomere length in PBMC	Positive	[120,121]
	↑ Antibody titer in response to influenza vaccination	Positive	[123–125]
	↑ NK cell function, T-cell number and lymphocyte proliferation	Negative	[126–128]
Resistance	↑ PBMC subpopulations, cytokine production, lymphocyte proliferation	Negative	[129–132]
	↑ DTH, NK cell cytotoxic activity; ↓ IL-6 serum concentration	Positive	[116]

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Can Exercise Be an Immunotherapy?

Innate Immunity & Immunosenescence

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