TLR-6 SNP P249S is associated with healthy aging in nonsmoking Eastern European Caucasians - A cohort study

Abstract

BackgroundTo investigate mechanisms that determine healthy aging is of major interest in the modern world marked by longer life expectancies. In addition to lifestyle and environmental factors genetic factors also play an important role in aging phenotypes. The aged immune system is characterized by a chronic micro-inflammation, known as inflamm-aging, that is suspected to trigger the onset of age-related diseases such as cardiovascular disease, Alzheimer’s disease, cancer, and Diabetes Mellitus Type 2 (DMT2). We have recently shown that a Toll-like receptor 6 variant (P249S) is associated with susceptibility to cardiovascular disease and speculated that this variant may also be associated with healthy aging in general by decreasing the process of inflamm-aging.ResultsAnalyzing the PolSenior cohort we show here that nonsmoking S allele carriers are significantly protected from age-related diseases (P = 0.008, OR: 0.654). This association depends not only on the association with cardiovascular diseases (P = 0.018, OR: 0.483) for homozygous S allele carriers, but is also driven by a protection from Diabetes Mellitus type 2 (P = 0.010, OR: 0.486) for S allele carriers. In addition we detect a trend but no significant association of this allele with inflamm-aging in terms of baseline IL-6 levels.ConclusionWe confirm our previous finding of the TLR-6 249S variant to be protective regarding cardiovascular diseases. Furthermore, we present first evidence of TLR-6 249S being involved in DMT2 susceptibility and may be in general associated with healthy aging possibly by reducing the process of inflamm-aging.

STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases

“…Smoking, past and current combined, showed no significant association ( p = 0.507) (Table 3). As reported previously, the past and current smoking subjects of our current cohort had a significantly lower age and BMI, which may counteract the risk of smoking [32]. A multivariate analysis of age, BMI, smoking, and microinflammation showed smoking also to be a significant risk factor for the occurrence of aging-related disease.…”

Hematopoiesis, Inflammation and Aging—The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals

“…Third, Makita et al [201] detected a gender difference with a significant association between carotid plaque score and high CRP levels only for men. Finally, even though CRP may not be an independent risk factor, it seems to be a part of a clinical high-risk inflammatory phenotype with complex interactions between several risk factors in elderly individuals, including smoking, diabetes, hypertension, body mass index, lipid metabolism and inherited differences in the regulation of inflammation [202,[205][206][207][208][209][210]. Gender differences with regard to the impact of CRP have been described only in some studies, but differences between men and women with regard to the associations between CRP levels and cardiovascular risk would not be unexpected because associations between CRP levels and male sex hormone levels have been described [211].…”