Role of senescence in the chronic health consequences of COVID-19

While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection).There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19.The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections.Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection.Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections.These processes may contribute to increased risk for restriction; FGA = Facility for Geroscience Analysis; ICU = intensive care unit; IF = intermittent fasting; LTCF = long-term care facility; MCC = multiple chronic conditions; MERS-CoV = Middle East Respiratory Syndrome Coronavirus; mTOR = mammalian target of rapamycin; NAD + = nicotinamide adenine dinucleotide; NMN = nicotinamide mononucleotide; NR = nicotinamide riboside; PACS = postacute sequalae of SARS-CoV-2 infection; PAMPs = pathogen-associated molecular profile factors; ROS = reactive oxygen species; SARS = severe acute respiratory syndrome; SARS-CoV-1 = severe acute respiratory syndrome coronavirus 1; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SASP = senescence-associated secretory phenotype; SNF = skilled nursing facility; TGN = translational geroscience network; WHO = World Health Organization