Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections

Abstract

The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, géros "old man" and epilavís, "harmful") infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.

Keywords: COVID-19; SARS-CoV-2; coronavirus; rapalog; sirolimus.

Figure 1

COVID-19 as a gerophilic and gerolavic infection. (A) Distribution of patients diagnosed in the city of Wuhan only through February 11, 2020. (B) Age distribution of the infected and diseased patients in Mainland China through February 11, 2020. The figures are adopted and generated from [12] (http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51).

Figure 2

The vicious circle of aging and infection, where age-associated immunosenescence leads to reduced ability to resist infection; infection leads to increased damage, loss of homeostasis, and accelerated aging; which in turn leads to age-related diseases, further accelerating immunosenescence. Infections and other age-related diseases are among the main causes of death in the developed world and developing countries.

Figure 3

Geroprotective and senoremediative strategies, such as a course of low-dose rapamycin, may potentiate the response to conventional prevention and treatment strategies, prevent infection, reduce disease severity and lethality, and may also increase longevity.

Figure 4

The timing of the administration of geroprotectors for prevention, treatment and rehabilitation of gerolavic respiratory diseases.