Figure 1.

Aging of the immune system: mechanisms and therapeutic strategies. (A, B) The immune system declines during aging, and its exposure to pathogens induces overstimulation and overreaction of immune cells (macrophages; lymphocytes B and T; natural killer and dendritic cells), releasing chemical mediators that affect their function and driving them toward immunosenescence and inflammaging. These processes accelerate the onset of age-related diseases reducing health span. (C) Aging alters immunity provoking unbalance between immunostimulatory and immunosuppressive mechanisms, which in turn impairs relevant functions of the immune system, including thymic involution, altered surface markers and phagocytosis of macrophages, decreased number and activity of B and T lymphocytes, telomerase shortening and DNA damage, reduced cytokine secretion, decreased mitochondrial biogenesis, and elevated ROS level. (D) All these changes ultimately cause dysfunction in different tissues and systems such as adipose, hepatic, and skeletal muscle tissues and cardiovascular and nervous systems. (E) Therapeutic strategies aimed to rejuvenate the immune system and decrease the risk of infectious diseases in elderly people are depicted. AP-1, activator protein 1; HIF-1α, hypoxia-inducible factor 1; IL1β, interleukin-1β; IL6, interleukin-6; NF-κB, nuclear factor kappa B; p38-MAPK, p38-mitogen activated protein kinase; PPAR-γ, peroxisome proliferator-activated receptor gamma; TNF-α, tumor necrosis factor-alpha. Created with BioRender.