Biomarkers of inflammaging in geriatric syndromes

The worldwide trend towards increasing life expectancy makes relevant the studies on aging and ageassociated pathology. The pathophysiologic mechanisms underlying geriatric syndromes remain insufficiently studied. It is hypothesized that chronic sterile inflammation (inflammaging) may be a key factor that links senile asthenia and sarcopenia. Several scientific teams are searching for biomarkers associated with different aging phenotypes. IL-1β, IL-6, TNFα, and C-reactive protein are among the most studied immunologic markers of aging. The study is devoted to a comprehensive evaluation of expression leveld of TLR2 patternrecognizing receptor gene as well as IL-1β, IL-6, IL-10 cytokine genes, and the contents of IL-1β, IL-6, IL-10 cytokines in long-livers with senile asthenia and sarcopenia. We included 219 nonagenarians who underwent a comprehensive geriatric evaluation according to current clinical guidelines. A subgroup including 161 patients meeting the homogeneity criteria for comorbidity was assessed by the Charlson comorbidity index. Further on, the clinical groups of long-livers were identified according to geriatric syndromes with the presence of senile asthenia (n = 77) and absence of frailty (n = 84); with sarcopenia (n = 130), and free of sarcopenia (n = 31). It was shown that the frailty is accompanied by increased expression of TLR2 gene, genes of proinflammatory cytokines IL-1β and IL-6, increased concentration of serum cytokine IL-6 compared to the group without this syndrome. It was found that sarcopenia is combined with increased IL6 gene expression, IL-1β and IL-6 cytokine production, and decreased gene expression and production of anti-inflammatory cytokine IL-10 compared to the group without sarcopenia. The ratio of IL-6/IL-10 cytokine concentration was found to be 5 times higher in long-livers with sarcopenia than in nonagenarians without sarcopenia, being 3.4 times higher in patients with senile asthenia than in nonagenarians without this syndrome. Increased IL-6/IL-10 ratio was associated with high probability of developing frailty and sarcopenia. Hence, the results of our study confirm the involvement of inflammatory aging in pathogenesis of geriatric syndromes in long-livers. The IL-6/IL-10 ratio, which characterizes the imbalance of pro- and anti-inflammatory factors in blood serum of nonagenarians, may be considered a potential marker of inflammation severity, evolving frailty and sarcopenia.