The burden of infectious disease falls most heavily upon the old. The attention given to COVID-19 has highlighted that point, though much of the media seems determined to avoid talking about the fact that near all mortality due to the condition occurs in the old and the cormorbid. It is nothing new, of course. Influenza kills tens of thousands of old people every year in the US alone, without much attention given to it. That the elderly suffer and die is old news. It is, however, old news that we should revisit in this era of revolutionary progress in medical biotechnology. The causes of aging and age-related mortality are amenable to treatment. The first rejuvenation therapies exist already, in the form of first generation senolytic treatments that destroy senescent cells.
COVID-19 mortality is strongly linked to inflammation. People with raised levels of chronic inflammation, such as the obese and the old, are much more vulnerable to suffering a runaway inflammatory event, a cytokine storm, and consequent severe illness and death. Today's open access paper is a novel consideration of this state of affairs that pulls in to this discussion what is known of the age-related dysfunction in coagulation. If a higher baseline inflammatory status leads to greater risk of severe inflammation due to infection, then, analogously, a greater baseline degree of dysfunction in mechanisms of coagulation leads to a greater risk of pathological disruption of coagulatory processes due to infection.
Older people with COVID-19 infection often suffer a severe form of interstitial pneumonia accompanied to an excessive human immune response with a hyper-inflammatory condition characterized by the increase of many plasma cytokines, including IL-6, interleukin 8 (IL-8), interferon (IFN), and tumor necrosis factor levels increase, particularly of IL-6 (the so-called "cytokine storm"). What drives such intense hyper-inflammation in COVID-19 is not yet known; however, the upregulation of IL-6 seems the pivotal pro-inflammatory function is contributing to COVID-19 severity.
Herein, we suggest that the preexisting upregulation of cytokine expression of inflammaging may trigger, and also support, the excessive hyper-inflammatory state in older people. Indeed, the superimposed SARS-CoV-2 infection in older adults may acutely exaggerate the already present pro-inflammatory background of inflammaging, predisposing older people to greater COVID-19 disease severity and mortality. The co-occurrence of the COVID-19 infection, constituting a second-hit to the preexisting pro-inflammatory condition of inflammaging, leading to a dysregulation of inflammation, which becomes harmful, reaching a severe pathological threshold.
We must also consider the impact of a pro-inflammatory state on coagulation because of the crosstalk between inflammation and coagulation. It is well established that the systemic inflammatory state of elderly people and coagulation disorder are closely linked, a phenomenon which here we refer to as "coagul-aging". Physiological aging is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment; this may be of great concern in view of the known association between vascular and thromboembolic diseases and aging, a condition which, here we suggest, may also contribute to the co-occurrence of the high incidence of coagulopathy in older COVID-19 patients.
In the future, we hope to carry out more studies on inflammaging and coagul-aging, which will enable us to understand the mechanism in-depth and find measures to intervene in the corresponding processes. More studies will not only help elderly patients with severe infections like COVID-19, but can also have the potential to intervene in the aging-associated pro-inflammatory state and the senescence process itself.