Lutz Hamann1, Juan S Ruiz-Moreno2, Malgorzata Szwed3, Malgorzata Mossakowska4, Linn Lundvall5, Ralf R Schumann5, Bastian Opitz2, Monika Puzianowska-Kuznicka3,6. 1. Department of Microbiology, Infectious Diseases, and Immunology, Charité - University Medical Center, Berlin, Germanylutz.hamann@charite.de. 2. Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - University Medical Center, Berlin, Germany. 3. Department of Human Epigenetics, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. 4. PolSenior Project, International Institute of Molecular and Cell Biology, Warsaw, Poland. 5. Department of Microbiology, Infectious Diseases, and Immunology, Charité - University Medical Center, Berlin, Germany. 6. Department of Geriatrics and Gerontology, Medical Center of Postgraduate Education, Warsaw, Poland.
Abstract
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.
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.
Authors: Patrick Kwabena Oduro; Xianxian Zheng; Jinna Wei; Yanze Yang; Yuefei Wang; Han Zhang; Erwei Liu; Xiumei Gao; Mei Du; Qilong Wang Journal: Acta Pharm Sin B Date: 2021-05-20 Impact factor: 11.413
Authors: James P Barrett; Susan M Knoblach; Surajit Bhattacharya; Heather Gordish-Dressman; Bogdan A Stoica; David J Loane Journal: Front Immunol Date: 2021-08-24 Impact factor: 7.561