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Gerontology. 2019;65(2):145-154. doi: 10.1159/000492972. Epub 2018 Oct 26.

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

Author information

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.

KEYWORDS:

Polymorphism; Senescence; cGAS-STING pathway

PMID:
30368497
DOI:
10.1159/000492972
[Indexed for MEDLINE]
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