COVID-19: A Challenge to Physiology of Aging

Abstract

The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. The same age-dependent mortality pattern known as the Gompertz law is featured by the total mortality and its main constituents attributed to cardiovascular, metabolic, neurological, and oncological diseases. Among patients dying of COVID-19, most have at least one of these conditions, whereas none is found in most of those who pass it successfully. Thus, gerontology is indispensable in dealing with the pandemic, which becomes a benchmark for validating the gerontological concepts and advances. The two basic alternative gerontological concepts imply that either aging results from the accumulation of stochastic damage, or is programmed. Based on these different grounds, several putative anti-aging drugs have been proposed as adjuvant means for COVID-19 prevention and/or treatment. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. In the pathophysiological terms, the conditions of the endothelium, which worsen as age increases and may be significantly improved by the physical activity, is a common limiting factor for the abilities to withstand both physical stresses and challenges imposed by COVID-19. However, the current anti-epidemic measures promote sedentary indoor lifestyles, at odds with the most efficient behavioral interventions known to decrease the vulnerability to both the severe forms of COVID-19 and the prevalent aging-associated diseases. To achieve a proper balance in public health approaches to COVID-19, gerontologists should be involved in crosstalk between virologists, therapists, epidemiologists, and policy makers. The present publication suggests a conceptual background for that.

Keywords: COVID-19; aging; anti-aging drugs; physiological balances; public health; signaling pathways; theories.

FIGURE 1

Age-specific rates of mortality attributed to COVID-19 (A) in the general population and (B) among hospitalized COVID-19 patients (case fatality rate) at different stages of the epidemic in the Netherlands. The Y-axes are semi-logarithmic. Data sources: “Epidemiologische situatie COVID-19 in Nederland” bulletins and Human Mortality Database (https://www.mortality.org/cgi-bin/hmd/country.php?cntr=NLD&level=1).

FIGURE 2

Age dependencies of the chances to become a registered COVID-19 patient in the Netherlands at two stages of the pandemic. Data sources: see Figure 1.

FIGURE 3

Attribution of the molecular targets of drugs suggested to treat both aging and COVID-19 (tan background) to signaling pathways from the availability of nutritional calories embodied in glucose to the physiological responses that allocate available resources between storage, growth and reproduction vs prevention and repair of molecular damage. Black solid lines designate mass transfer. Thin lines designate influences without specifying their mechanisms. Some may involve additional steps and intermediates, which are not shown. Blue arrows stand for activation or enhancement. Red bricks stand for inhibition or suppression. Abbreviations are explained in the main text.