Inflammaging in the Inner Ear, a Path to Hearing Loss
Inflammaging is a blanket term for the inappropriate inflammatory reaction of the immune system to the accumulation of molecular damage and other changes that take place with age. Constant, low-grade, unresolved inflammatory activation of the immune system is a feature of aging. It alters cell behavior for the worse and is disruptive to tissue structure and function. A number of different mechanisms contribute to forming and maintaining the state of inflammaging, such as pro-inflammatory signaling produced by ever-larger numbers of senescent cells, and innate immune recognition of mislocalized mitochondrial DNA that results from mitochondrial stress and dysfunction. It seems likely that progress in stopping inflammaging will only emerge from ways to address the mechanisms that cause aging, like those mentioned above. Clear the senescent cells, repair or replace the mitochondria, and so forth.
In today's open access review paper, researchers discuss inflammaging as a contribution to age-related hearing loss. Chronic inflammation and the problems that follow in its wake can be found throughout the body; one could point to dozens of papers much like this one, each focused on the consequences of chronic inflammation in a single organ or tissue. Controlling inflammaging, shutting it down while still preserving the normal, transient inflammatory response to infection and damage, is a very necessary goal in the treatment of aging as a medical condition.
Age-related hearing loss (ARHL) is one of the most common health disorders in the aging population, affecting over a third of adults over age 65. Recently, dysregulation of the immune system has come into light as a major pathological driver of ARHL. The term "inflammaging" describes the low-grade, sterile, chronic inflammatory state in the body's tissues with age. Chronic inflammation plays a role in multiple systemic diseases such as diabetes, as well as neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and retinal degeneration.
During aging, immune cells undergo senescence, a process in which they lose the ability both to mount the normal immune response and to resolve inflammation after acute insults. Increased systemic levels of inflammatory markers, including C-reactive protein, interleukin-6 (IL-6), and white blood cell counts, are observed in neurodegenerative processes and ARHL, suggesting that inflammation is a hallmark of the aging brain and inner ear. Newer studies are exploring the role of gut microbiota in inflammaging, noting how pro-inflammatory diets such as foods high in sugar correlate with systemic inflammatory markers and severity of hearing loss. Conversely, long-term exercise is thought to delay progression of neurodegenerative processes and ARHL through the dampening of inflammation. Inflammaging can impair neural and sensory networks through several interrelated processes, many of which have been well-characterized in neurodegenerative diseases. Similar mechanisms are now being elucidated in ARHL as well.
This brief review summarizes current research on the cellular and molecular components of the innate immune system in ARHL, including the role of inflammatory cytokines, chemokines, inflammasomes, the classical complement pathway, and macrophages, as well as the interactions of each of these players with inner ear sensory structures. It also discusses emerging research of the involvement of the adaptive immune system in ARHL which thus far has largely been overlooked. A better understanding of immunosenescence in ARHL can elucidate future therapeutic avenues for a very prevalent and debilitating condition that currently has no preventative medicines or molecular treatments that target its underlying pathology.