COVID-19 and Crosstalk With the Hallmarks of Aging

Abstract

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen-host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host-coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.

Keywords: Aging; Antiaging; COVID-19; Comorbidity; Hallmarks of aging; Pandemic.

Figure 1.

The schematic figure implies the interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the cell structures, clockwise including cell membrane, endoplasmic reticulum, Golgi, extracellular matrix, followed by hallmarks of aging such as senescence cells, inflammation, genome instability, mitochondrial function, telomere length, epigenetics, and stem cell exhaustion. The entire cell fitness is required to combat viral infection, and coronavirus engages cell systems.

Figure 2.

(a) Key SARS CoV-2 proteins implicated in COVID-19. The viral genome encodes 29 proteins among which at least 13 have been implicated in its virulence. (b) Coronavirus structure, cell entry, and replication. ACE2 = angiotensin-converting enzyme 2; ERGIC = endoplasmic reticulum–Golgi intermediate compartment; ER = endoplasmic reticulum.

Figure 3.

Mitochondria, outer membrane permeability, and apoptosis pathways. Apoptosis induced by coronavirus infection, including intrinsic and extrinsic apoptosis. FasL = Fas ligand; TNF-α = tumor necrosis factor-alpha. Antiapoptotic factors: Bcl-xL = Bcl-2-like protein 1; Bcl2 = B-cell lymphoma 2; Mcl1 = myeloid cell leukemia 1. Proapoptotic factors: PUMA = p53-upregulated modulator of apoptosis; BAD = Bcl2-associated agonist of cell death; BAX = Bcl2-associated X; BIM = Bcl2-interacting mediator of cell death; APAF1 = apoptotic peptidase-activating factor 1; Casp = caspase; FADD = Fas-associated via death domain; AKT = RAC-alpha serine/threonine protein kinase; IL = interleukin; IRFs = interferon regulatory factors; MAVS = mitochondrial antiviral-signaling proteins; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; RIG-I = retinoic acid-inducible gene I; SARS = severe acute respiratory syndrome (70).