From causes of aging to death from COVID-19

Abstract

COVID-19 is not deadly early in life, but mortality increases exponentially with age, which is the strongest predictor of mortality. Mortality is higher in men than in women, because men age faster, and it is especially high in patients with age-related diseases, such as diabetes and hypertension, because these diseases are manifestations of aging and a measure of biological age. At its deepest level, aging (a program-like continuation of developmental growth) is driven by inappropriately high cellular functioning. The hyperfunction theory of quasi-programmed aging explains why COVID-19 vulnerability (lethality) is an age-dependent syndrome, linking it to other age-related diseases. It also explains inflammaging and immunosenescence, hyperinflammation, hyperthrombosis, and cytokine storms, all of which are associated with COVID-19 vulnerability. Anti-aging interventions, such as rapamycin, may slow aging and age-related diseases, potentially decreasing COVID-19 vulnerability.

Keywords: COVID-19; SARS-CoV-2; aging; coronavirus; mTOR; rapalogs; senolytics.

Figure 1

Cytokine storm as a systemic hyperfunction.

Figure 2

Quasi-programmed hyperfunctional aging. Aging is a continuation of developmental programs that were not switched off upon their completion. An increase in cellular and systemic functions (manifested as pre-diseases and then as diseases) leads to eventual organ damage and secondary loss of function.

Figure 3

COVID-19 vulnerability as an age-related disease. Age-related diseases, including COVID-19 vulnerability, are manifestations of aging. Abbreviations: Ischemic heart disease (IHD); Chronic obstructive pulmonary disease (COPD).

Figure 4

Rejuvenating immunity by inhibiting hyperfunction. (A) Specific hyper-functional cells (or signaling pathways) can inhibit some other cell types (or pathways) that are needed for proper anti-viral response and immunization. (B) By inhibiting hyper-functional cells or pathways, rapamycin can reactivate “loss-of-function” otherwise suppressed by hyper-functional cells or pathways.

Figure 5

Prevention of COVID-19 vulnerability by staying young. Hypothetical graph in the absence of COVID-19. COVID-19 vulnerability (log scale) increases exponentially with age (blue line). The line ends at age 120, a maximum recorded age for humans. In theory, a continuous rapamycin treatment would slow down an increase of the vulnerability with age (red line). The increase is still logarithmic but at a different slope, because rapamycin slows the aging process. The maximum lifespan, in the absence of COVID-19, is extended because the 100% natural death threshold is achieved later.