Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an archetype of systemic autoimmune disease, characterized by the presence of diverse autoantibodies and chronic inflammation. There are multiple factors involved in lupus pathogenesis, including genetic/epigenetic predisposition, sexual hormone imbalance, environmental stimulants, mental/psychological stresses, and undefined events. Recently, many authors noted that “inflammaging”, consisting of immunosenescence and inflammation, is a common feature in aging people and patients with SLE. It is conceivable that chronic oxidative stresses originating from mitochondrial dysfunction, defective bioenergetics, abnormal immunometabolism, and premature telomere erosion may accelerate immune cell senescence in patients with SLE. The mitochondrial dysfunctions in SLE have been extensively investigated in recent years. The molecular basis of normoglycemic metabolic syndrome has been found to be relevant to the production of advanced glycosylated and nitrosative end products. Besides, immunosenescence, autoimmunity, endothelial cell damage, and decreased tissue regeneration could be the results of premature telomere erosion in patients with SLE. Herein, the molecular and cellular bases of inflammaging and cardiovascular complications in SLE patients will be extensively reviewed from the aspects of mitochondrial dysfunctions, abnormal bioenergetics/immunometabolism, and telomere/telomerase disequilibrium.

Influenza Vaccination to Reduce Cardiovascular Morbidity and Mortality in Patients With COVID-19

“…“Immunosenescence” refers to an altered immune response seen with increasing age and many chronic medical conditions, including cancer, autoimmune diseases, and CVD ( 75 , 76 , 77 , 78 ). Inflammaging refers to the chronic, sterile, low-grade inflammation seen with increasing age, and implicated in the pathogenesis of chronic age-related diseases, like CVD ( 79 ).…”

Cross-Talk between Mitochondrial Dysfunction-Provoked Oxidative Stress and Aberrant Noncoding RNA Expression in the Pathogenesis and Pathophysiology of SLE

“…These mitochondrial functional abnormalities may further increase oxidative stress and cell apoptosis in patients with SLE, in addition to the defective bioenergetics. Yang et al [110] and Tsai et al [111] concluded that enhanced oxidative stress could facilitate mitophagy, inflammatory reactions, cell senescence/apoptosis, neoantigen formation, and NETosis in SLE. The causes of mitochondrial dysfunction to induce excessive oxidative stresses and their effects on the lupus pathogenesis and pathological processes are illustrated in Figure 3.…”

“…As a consequence, the resulting sensitivity to environmental stress and sex hormone dysregulation [26,27,28,29,30,31] may further trigger the occurrence of lupus flare-ups. In addition, cardiovascular morbidities are enhanced due to increased glycation end products in patients with SLE [111,112,115]. The molecular basis and adverse effects of excessive oxidative stress in lupus pathogenesis and pathology are summarized in Figure 4.…”

Kollagenosen und Psychoneuroimmunologie – Beispiel systemischer Lupus erythematodes

“…Die bei SLE dauerhaft angestiegenen Entzündungslevel (z. B. IL6 und IL10 [23]) schränken langfristig nicht nur die Lebenserwartung ein ("Inflammaging" [24,25]), sondern stehen auch im Verdacht, der Grund für unterschiedliche bei SLE und anderen AIK häufig vorkom menden chronischen neurovegetativen und psychiatrischen Be gleitbeschwerden zu sein (z. B.…”