Why is Sepsis a Condition of the Elderly?

Sepsis and consequent septic shock occur more frequently in the old and cause greater harm and mortality in older individuals. The condition occurs when an infection spurs the immune system into a state of runaway inflammation and then shutdown, sufficient to disrupt or permanently damage metabolism and organ function. The open access paper here dives into the details of age-related immune system dysfunction, with an eye to explaining why exactly these failures cause sepsis to be both worse and more prevalent in the elderly. As for so many of the specific frailties of old age, the best solution is to repair the immune system - to address the specific, most important root causes of its decline, such as failing blood stem cells, atrophy of the thymus, and accumulation of malfunctioning or overspecialized immune cells.

The treatment of critically ill aged patients is challenging. Older people frequently exhibit atypical symptomatology, due to comorbidities and dysfunctions throughout all body systems that are related to the aging process. Sepsis is a disease of the elderly. The incidence of sepsis increases exponentially with age, and sepsis-associated long-term sequelae particularly affect older patients. Sepsis survivors are at substantial risk for poor quality of life, functional disability, and cognitive impairment. As advances in medicine and quality of life extend the life expectancy worldwide, a growing number of aged patients need critical care. A recent study demonstrated a significant rise in survivorship after sepsis in the United States, caused by a rising incidence of sepsis rather than improvements in its case fatality rate, generating a substantial population burden of aged patients with disabilities.

The reason for the higher susceptibility to infection and increased mortality in older adults remains in debate. The basal inflammatory state found in healthy seniors suggests that aged people possess a limited capacity to control inflammation. Similarly, the critically ill are frequently affected by overwhelming inflammatory syndromes, where the host response is the major cause of damage. The chronic low-grade inflammation in the elderly and the explosive inflammation in the critically ill share several commonalities. We propose that, together, these processes may have synergistic effects, leading to a worse outcome.

Notably, these synergistic effects have interesting peculiarities. A study performed by our group found that older people are as immunocompetent as young individuals regarding the cytokines, chemokines, and growth factors produced in response to devastating infections. After our analysis of several inflammatory mediators in the plasma of critically ill individuals, we were unable to find any reason that could serve to better explain why the aged show an increased susceptibility and mortality to septic shock. This phenomenon can be partially explained by the fact that aged people probably display a prolonged inflammatory systemic response under acute stress conditions, when compared with the systemic response of the young, even though both groups share the same ability to trigger and sustain the same intensity of inflammatory signaling in the acute phase.

The intestinal mucosal barrier is a fundamental line of defense against undesirable microorganisms, toxins, and antigens, preventing their entrance into the bloodstream. Aged people are in a persistent systemic inflammatory state that may be partially attributed to increased bacterial translocation, secondary to intestinal barrier dysfunction. As people age, the intestinal barrier weakens, partially due to decreased levels of tight junctions connecting epithelial cells, and the enteric immune system becomes ineffective. These observations suggest that the increased mortality of aged patients in critical care conditions is probably due to a prolonged systemic inflammatory response, at least partially caused by increased bacterial translocation and defective bacterial clearance.

Link: https://doi.org/10.3389/fimmu.2017.01389


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