Immunosenescence, Inflammaging, and Frailty: Role of Myeloid Cells in Age-Related Diseases

Abstract

The immune system is the central regulator of tissue homeostasis, ensuring tissue regeneration and protection against both pathogens and the neoformation of cancer cells. Its proper functioning requires homeostatic properties, which are maintained by an adequate balance of myeloid and lymphoid responses. Aging progressively undermines this ability and compromises the correct activation of immune responses, as well as the resolution of the inflammatory response. A subclinical syndrome of “homeostatic frailty” appears as a distinctive trait of the elderly, which predisposes to immune debilitation and chronic low-grade inflammation (inflammaging), causing the uncontrolled development of chronic and degenerative diseases. The innate immune compartment, in particular, undergoes to a sequela of age-dependent functional alterations, encompassing steps of myeloid progenitor differentiation and altered responses to endogenous and exogenous threats. Here, we will review the age-dependent evolution of myeloid populations, as well as their impact on frailty and diseases of the elderly.

How Can We Improve Vaccination Response in Old People? Part I: Targeting Immunosenescence of Innate Immunity Cells

“…The combination of these events contributes to an enhanced status of inflammaging and may be a possible explanation for the greater susceptibility of the older people to invasive bacterial infections [ 23 ]. The majority of these events can be detected following in vitro stimulation with formyl-methionine-leucine-phenylalanine, lipopolysaccharide (LPS), and granulocyte–macrophage colony-stimulating factor (GM-CSF) [ 26 ].…”

Cellular Senescence in Immunity against Infections

“…In addition, a recent study revealed that aging alters critical pathways important in the production of type I interferon in CD14 dim CD16 + monocytes, resulting in impaired innate immune responses to pathogen recognition receptor (PRR) agonists [ 108 ]. The frequency of circulating myeloid-derived suppressor cells (MDSCs) increases with age in both humans and mice [ 109 ]. Interestingly, proinflammatory factors produced by senescent cells promote both the proliferation and activation of MDSCs, which, in turn, secrete the anti-inflammatory cytokine TGF-β, a potent inducer of cellular senescence in inflamed tissues [ 110 ].…”

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

“…Among these factors, IL-1, IL-6 and TNF-α remarkably support cancer growth and spreading (Jobe et al 2016;Bleve et al 2022;Strnadová et al 2022). IL-6 represents a direct link between autoimmune disorders, cancer and age-related diseases, thus offering an attractive therapeutic target (Iorio et al 2021).…”