title: Less functional variants of TLR-1/-6/-10 genes are associated with age.
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.
authors.affiliation: Institute of Microbiology and Hygiene, Charité University Medical Center Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Hamann
authors.affiliation: Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Juozas
authors.initials: J
authors.lastname: Kupcinskas
authors.affiliation: Institute of Microbiology and Hygiene, Charité University Medical Center Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Luis C
authors.initials: LC
authors.lastname: Berrocal Almanza
authors.forename: Berrocal
authors.initials: B
authors.lastname: Almanza
authors.affiliation: Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Skieceviciene
authors.affiliation: University Hospital Schleswig Holstein, Campus Kiel, Schittenhelmstr. 12, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: 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.
authors.forename: Ute
authors.initials: U
authors.lastname: Nöthlings
authors.affiliation: Institute of Microbiology and Hygiene, Charité University Medical Center Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
keywords: Healthy aging; Inflamm-aging; Innate immunity; Polymorphisms; Toll-like receptors