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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.

Author information

1
Institute of Microbiology and Hygiene, Charité University Medical Center Berlin, Charitéplatz 1, 10117 Berlin, Germany.
2
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
3
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
4
University Hospital Schleswig Holstein, Campus Kiel, Schittenhelmstr. 12, Kiel, Germany.
5
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.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

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