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.
Highlights
The strikingly high share of elderly people among COVID19 victims (Mueller et al, 2020) and the so-called cytokine storm implicated in such cases (Alijotas-Reig et al, 2020; Daneshkhah et al, 2020; Meftahi et al, 2020) are contributing to a severe scholarly publications tempest
A fairly stable character of the pandemic has been recognized (Golubev and Sidorenko, 2020; Guilmoto, 2020; Promislow, 2020; Santesmasses et al, 2020): in different countries and at different stages of the epidemic there, COVID-19 patients at ages (a) ranging from 30 to 80 years feature an exponential pattern of increase in mortality rate upon increasing a: f (a) = f0 × eY×a or ln f (a) = ln f0 + Y × a
Its low variability makes the doubling time (DT) of case fatality rate (CFR) (DT = ln2/Y) to vary only from 6 to 8 years, as has been shown in the papers referenced above, whose authors have recognized this mortality pattern as consistent with the dependency of general mortality on age, which is known in gerontology as the Gompertz law or model: ln μ(t) = ln μ0 + Y × t, where μ is mortality rate, t is the chronological age, and γ is interpreted as the rate of aging
Summary
The strikingly high share of elderly people among COVID19 victims (Mueller et al, 2020) and the so-called cytokine storm implicated in such cases (Alijotas-Reig et al, 2020; Daneshkhah et al, 2020; Meftahi et al, 2020) are contributing to a severe scholarly publications tempest. Doubling times related to CFR (DT) and to the total mortality rate in the general population (MRTD) are similar in all cases, in conformance to what has been shown earlier using less detailed data on COVID-19 epidemics in Italy, Spain and Sweden (Golubev and Sidorenko, 2020), China, South Korea, and USA (Santesmasses et al, 2020), and West Europe and North America in general (Guilmoto, 2020). To delineate feedback loops able to translate primary agedependent decreases in the functions of defined leukocyte populations into secondary increases in the levels of interleukins implicated in the cytokine storm, one must wander through all possible interleukin-mediated pathways that control immune responses This daunting task is far beyond the scope of the present discussion, whose main objective is limited to pinpointing the overlaps between the basic issues of COVID-19 research and gerontology. Without delving into mechanistic details, which are still not clear, it is possible to conclude from the above that the molecular targets of metformin are engaged in shifting the use of cell resources from storage, growth and reproduction to turnover, which is associated with elimination of damage, to counteracting the processes that make damage and to activating the mechanisms that repair damage
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