As part of our growing focus on healthy aging at NeuroScience, Inc., here’s what’s on our radar: Immunosenescence, which is a fancy way of saying “aging of the immune system”.
While you might not give immunosenescence a second thought (because all biological systems age, right?), several interesting findings suggest that immunosenescence is not strictly associated with chronological age. There are very old people out there with youthful-looking immune systems, and on the other hand, premature immunosenescence has been observed in the under-fifty set.
Immunosenescence is definitely cause for concern. Unilever’s Steve Wilson and Dawn Mazzatti note that “the production of high levels of pro-inflammatory cytokines and alterations in immunity … are thought to underlie the progression of chronic degenerative diseases of aging, such as atherosclerosis, Type 2 diabetes and Alzheimer’s disease.” UCLA’s Rita Effros writes, “Aging of the immune system is a major factor responsible for the increased severity of infections, reduced responses to vaccines, and higher cancer incidence in the elderly.” Provinciali et al. concur, reviewing data indicating that persistent inflammation increases the risk of cancer and its progression.
What does immunosenescence look like? Research is showing us that an aging immune system is characterized by a number of functional alterations and cellular characteristics, in what is collectively termed an ‘immune risk profile’, or IRP, by Evelyna Derhovanessian and her colleagues. Larbi et al. summarized many of the changes in T and B cell function in this table from their 2008 paper, and here are the findings by other investigators:
- Decreased numbers of T cells (perhaps particularly CD4+ T helper cells) and B cells
- Decreased function of immune cells, including
- T cells – impaired delayed-type hypersensitivity
- B cells – reduced ability to generate antibody responses, which is why vaccinations are often not as effective in the elderly
- Natural killer cells – reduced cytolytic activity and interferon-gamma production (we’ve discussed NK cells in an earlier post)
- Macrophages and neutrophils – decreased phagocytosis, which is an important means whereby these innate immune cells “eat” pathogens and dying cells
- Dendritic cells – decreased responsiveness to microbial signals that is often the first step in kicking off an immune response (Panda et al., 2010; Rosenstiel et al., 2008)
- A shift in the expression of particular lymphocyte cell surface markers, including the loss of CD28-expressing cells, and an increase in cells expressing CD95 and/or the terminal differentiation marker CD57.
- Elevated proinflammatory cytokines and CRP levels indicative of a chronic state of low-grade inflammation
- Seropositivity for viruses such as CMV
- Low intracellular zinc content
- Elevated cortisol, and perhaps especially an elevated cortisol/DHEA ratio
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