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Immun Ageing. 2015 Jul 8;12:7. doi: 10.1186/s12979-015-0034-z. eCollection 2015.

Less functional variants of TLR-1/-6/-10 genes are associated with age.

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Institute of Microbiology and Hygiene, Charité University Medical Center Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
University Hospital Schleswig Holstein, Campus Kiel, Schittenhelmstr. 12, Kiel, Germany.
Popgen Biobank, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, Niemansweg 11, Kiel, Germany ; Present address: Department of Nutrition and Food Sciences, Rheinische Friedrich-Wilhelms-University Bonn, Endenicher Allee 11-13, 53115 Bonn, Germany.



Determining the prerequisites for healthy aging is a major task in the modern world characterized by a longer lifespan of the individuals. Besides lifestyle and environmental influences genetic factors are involved as shown by several genome-wide association studies. Older individuals are known to have an impaired immune response, a condition recently termed "inflamm-aging". We hypothesize that the induction of this condition in the elderly is influenced by the sensitivity of the innate immune system. Therefore, we investigated genetic variants of the Toll-like receptor (TLR) family, one of the major family of innate immune receptors, for association with age in two cohorts of healthy, disease-free subjects.


According to sex we found a positive association of loss-of-function variants of TLR-1 and -6 with healthy aging with odds ratios of 1.54 in males for TLR-6 (249 S/S), and 1.41, 1.66, and 1.64 in females for TLR-1 prom., TLR-1 (248 S/S), and TLR-1 (602 S/S), respectively. Thus, the presence of these variants increases the probability of achieving healthy old age and indicates that a reduced TLR activity may be beneficial in the elderly.


This is the first report showing an association of TLR variants with age. While a loss of function of an important immune receptor may be a risk factor for acute infections as has been shown previously, in the setting of healthy ageing it appears to be protective, which may relate to "inflamm-aging". These first results should be reproduced in larger trials to confirm this hypothesis.


Healthy aging; Inflamm-aging; Innate immunity; Polymorphisms; Toll-like receptors

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