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

Background: Aging is a multifactorial process driven by several conditions. Among them, inflamm-aging is characterized by chronic low-grade inflammation driving aging-related diseases. The aged immune system is characterized by the senescence-associated secretory phenotype, resulting in the release of proinflammatory cytokines contributing to inflamm-aging. Another possible mechanism resulting in inflamm-aging could be the increased release of danger- associated molecular patterns (DAMPs) by increased cell death in the elderly, leading to a chronic low-grade inflammatory response. Several pattern recognition receptors of the innate immune system are involved in recognition of DAMPs. The DNA-sensing cGAS-STING pathway plays a pivotal role in combating viral and bacterial infections and recognizes DNA released by cell death during the process of aging, which in turn may result in increased inflamm-aging. Objective: The aim of this study was to investigate whether a variation within the STING gene with known impaired function may be associated with protection from aging-related diseases by decreasing the process of inflamm-aging. Methods: STING (Tmem173) R293Q was genotyped in a cohort of 3,397 aged subjects (65–103 years). The distribution of the variant allele in healthy subjects and subjects suffering from aging-associated diseases was compared by logistic regression analysis. Results: We show here that STING 293Q allele carriers were protected from aging-associated diseases (OR = 0.823, p = 0.038). This effect was much stronger in the subgroup of subjects suffering from chronic lung diseases (OR = 0.730, p = 0.009). Conclusion: Our results indicate that decreased sensitivity of the innate immune receptors is associated with healthy aging, most likely due to a decreased process of inflamm-aging.