The Threat of Sepsis in Old Age

Sepsis is a disastrous runaway failure state of the immune system and metabolism that can occur in the wake of a severe infection. It leads to organ failure and can rapidly kill you even if the infection that caused it is dealt with. Sepsis is more of a looming threat for the old than the young, those with age-damaged immune systems and other frailties. For all this, it isn't something that receives all that much attention in comparison to other common fatal age-related conditions such as heart failure and cancer. With that in mind, here is an open access paper that provides an overview of the present state of knowledge of sepsis, while introducing us to the gloomy situation that exists with regards to treatment options for sepsis in the old:

Sepsis in Old Age: Review of Human and Animal Studies

Sepsis is a serious problem among the geriatric population as its incidence and mortality rates dramatically increase with advanced age. Despite a large number of ongoing clinical and basic research studies, there is currently no effective therapeutic strategy that rescues elderly patients with severe sepsis. Recognition of this problem is relatively low as compared to other age-associated diseases.

Sepsis has been the tenth leading cause of death in patients over the age of 65 in the US since 2001. Older people make up a greater proportion (58-65%) of sepsis patients, and both incidence and mortality rates are significantly greater in the aged. Importantly, in addition to increased mortality rates for the elderly, older sepsis patients die earlier during hospitalization, and those that do survive often require additional care in long-term nursing facilities to regain functional status.

A recent study evaluated long-term mortality in elderly severe sepsis patients (only those surviving at three months post sepsis were included) and found an overall mortality rate of 55% with a 30.6% one-year morality rate and a 43% two-year mortality rate. This means that more than half of the elderly patients who survive sepsis through hospital discharge will be dead within two years.

The authors here suggest that many of the present issues in the sepsis research community - lack of progress towards more effective treatments foremost among them - stem from a poor choice of animal models used in studies.

The incidence of sepsis increases exponentially from childhood to geriatric age with a magnitude of approximately 100-times. Mortality from sepsis also increases progressively with age. The incidence of sepsis is steadily increasing as our population ages. Despite these problems, little is known about the pathophysiology of sepsis which is specific to older patients.

Sepsis patients, in addition to being a heterogeneous population, have large variations in disease course factors including severity, source of infection, comorbidities, and timing of hospital admission. While caution has to be paid for biological differences between men and rodents, the use of laboratory animals is essential for understanding the detailed pathophysiology of sepsis.

Despite the fact that there is clearly an increased precedence of elderly patients suffering from sepsis, the majority of basic research on sepsis has been conducted using young animals. This mismatch introduces a serious disconnect in interpretation of sepsis studies using mice or men because most humans with sepsis are over 50 years old, and most mice used in sepsis research are less than 3 months old, comparable to a person under 20 years of age.

For example, immune responses to infection are clearly altered by aging, thus, the use of aged animals in sepsis research would provide important information that would greatly differ from data obtained using young animals. The number of studies on sepsis using aged animals (i.e. rodents) is surprisingly small. By utilizing the PubMed journal search engine, we estimate that among all published studies using animal models of sepsis, less than 1% used appropriately aged animals.

The paper goes into greater detail as to noteworthy differences in the progression and character of sepsis between young and old individuals, and explains why these differences matter in practice. It's worth reading the whole thing.


Hopefully this will be resolved to a significant degree by thymic rejuvination or replacement and T and B cell ablation.

Posted by: Jim at April 25th, 2014 5:28 AM

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