Immunological Functions of Aged Human Monocytes

Abstract

Aging is associated with an increased occurrence of infection and cancer, and, as people age, they begin to exhibit age-related immune deficiencies, collectively termed immunosenescence. To determine the effects of age on human monocytes, ‘aged monocytes’ (isolated from individuals > 65 years of age) were compared with ‘young monocytes’ (isolated from individuals -25 years of age) for their ability to be activated by lipopolysaccharide. Our results show that aged monocytes display a decrease in their cytotoxicity against tumor cells in vitro, a decrease in interleukin (IL1) secretion (although no decrease in IL1 precursor production was observed), a decrease in reactive oxygen and nitrogen intermediate (ROI/RNI) release, an increase in intracellular levels of cyclic adenosine monophosphate and a loss of protein kinase translocation. Therefore, aged monocytes present distinct characteristics of immunosenescence.

Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone

“…Defective PKC activation with aging has also been reported by several authors in human monocytes [18,19] and in human T lymphocytes [20,21], and ϳ50% of elderly subjects has significant reduction in PKC activity in B cells [22]. Agerelated impairment of the translocation of PKC is likely to underlie downstream defects in the activation of immune responses in vitro, as diminished generation of cytotoxic effectors, lower production of some cytokines, and reduced proliferative responses, and in vivo, as diminished response to vaccination and increased susceptibility to infections.…”

Fat accumulation with altered inflammation and regeneration in skeletal muscle of CCR2−/− mice following ischemic injury

“…Furthermore, aged mice (12,39,59), similar to elderly humans (3,37), have alterations in macrophage function. Thus CCR2Ϫ/Ϫ mice may represent a unique animal model for studies designed to elucidate the inflammation-based mechanisms involved in impaired skeletal muscle regeneration that may occur in normal human aging.…”

Effect of Senescence on Macrophage Polarization and Angiogenesis

“…39,40 The effect of aging on macrophages is not restricted to mice, as human monocytes from aged individuals are reported to display decreased cytotoxicity against tumor cells in vitro after LPS stimulation, corresponding with decreased release of reactive oxygen and nitrogen intermediates. 41,42 Macrophages may also actively contribute to dysregulated immune function by their secretion of immunosuppressive substances, particularly prostaglandins (PGE). Macrophages from old mice have higher PGE 2 production than those from young mice.…”