Role of senescence in the chronic health consequences of COVID-19.
Translational research : the journal of laboratory and clinical medicine. 2022;:96-108
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 long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.
Magnesium in Infectious Diseases in Older People.
Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.
Does eNOS derived nitric oxide protect the young from severe COVID-19 complications?
Ageing research reviews. 2020;:101201
The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. Nevertheless, low type I and III IFNs are generally observed in COVID-19 patients suggesting that other intracellular viral defence systems are also activated to protect the young. Intriguingly, Nitric oxide (NO), which is the main intracellular antiviral defence, has been shown to inhibit a wide array of viruses, including SARS-CoV-1. Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism. NO decreases dramatically in the elderly, the hyperglycaemic and the patients with low levels of vitamin D. However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. Intriguingly, the inverse correlation between the percentage of WT eNOS haplotype and death per 100K population could potentially explain the disparity of COVID-19 mortality between Asian and non-Asian countries. These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.
Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis.
Journal of infection and public health. 2020;(9):1196-1201
The aging-associated decline of biological functions represents an important contributor to the increase in morbidity and mortality of human beings. Of these biological functions deterioration; there is a significant decline in the heart function, impairments in the lungs gas exchange, and impairments in the immune function. Many alterations in the body humeral and cellular immune response were observed with ageing process: The circulating pro-inflammatory cytokines are increased, the naive lymphocytes are decreased, the numbers of the antigen-presenting cells areelevated and the overall response is impaired. In addition, ageing is associated with a progressive restriction in the telomere length. Telomeres are located at chromosomes ends and play an essential role in preserving chromosome stability. Also, telomere length is very important to the immune system, because of the high sensitivity of the immune cells to the shortening of telomeres. Telomeres shortening adversely affect the immune cells' function and developments. These adverse changes increased the susceptibility for severe infection, risk of hospitalization, and even death. Elderly COVID-19 patients are at a real risk of complications due to impaired immune function, cytokine storm and defective respiratory function. Administration of anti-ageing immunomodulation factors like Nicotinamide Adenine Dinucleotide NAD+ can minimize these changes through its potent immunomodulation and longevity effects. NAD+ has a direct inhibitory effect on PARP-1 and can prevent pro-inflammatory cytokines over-activation. Increasing the NAD+ level will also result in stabilizing telomeres and this has a positive impact on immune cells function.