Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the... Show moreClear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10(-8) ). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. Show less
BACKGROUND reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is... Show moreBACKGROUND reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is important to know both the extent and limitations of this association. We investigated the relation between telomere length and anaemia in two independent cohorts, with the prior expectation of adding anaemia to the list of conditions for which telomere reduction is a risk factor. PARTICIPANTS AND METHODS the present study is embedded in the Newcastle 85-plus Study and Leiden 85-plus Study, two population-based studies of inhabitants of Newcastle and North Tyneside, UK (n = 749) and Leiden, the Netherlands (n = 658) aged 85 and over. High-molecular-weight DNA was isolated from full fresh blood (Newcastle) and peripheral blood mononuclear cells samples (Leiden). Telomere length was measured as abundance of telomeric template versus a single gene by quantitative real-time polymerase chain reaction. Anaemia was defined according to World Health Organization criteria. RESULTS in both studies, no differences in median telomere length were observed between participants with anaemia and participants without anaemia (Newcastle: 2,846 bp (interquartile range (IQR) 2,433-3,630) versus 2,920 bp (IQR 2,425-3,570), P = 0.63; Leiden: 4,136 bp (IQR 3,879-4,428) versus 4,167 bp (IQR 3,893-4,501), P = 0.41). Telomere length also did not correlate with any other haematological parameter in both men and women. CONCLUSIONS in contrast to other age-related diseases, telomere length is not associated with anaemia or any other haematological parameter in older individuals in the general population. Show less
Elzen, W.P.J. den; Martin-Ruiz, C.; Zglinicki, T. von; Westendorp, R.G.J.; Kirkwood, T.B.L.; Gussekloo, J. 2011
Background: reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is... Show moreBackground: reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is important to know both the extent and limitations of this association. We investigated the relation between telomere length and anaemia in two independent cohorts, with the prior expectation of adding anaemia to the list of conditions for which telomere reduction is a risk factor. Participants and methods: the present study is embedded in the Newcastle 85-plus Study and Leiden 85-plus Study, two population-based studies of inhabitants of Newcastle and North Tyneside, UK (n = 749) and Leiden, the Netherlands (n = 658) aged 85 and over. High-molecular-weight DNA was isolated from full fresh blood (Newcastle) and peripheral blood mononuclear cells samples (Leiden). Telomere length was measured as abundance of telomeric template versus a single gene by quantitative real-time polymerase chain reaction. Anaemia was defined according to World Health Organization criteria. Results: in both studies, no differences in median telomere length were observed between participants with anaemia and participants without anaemia (Newcastle: 2,846 bp (interquartile range (IQR) 2,433-3,630) versus 2,920 bp (IQR 2,425-3,570), P = 0.63; Leiden: 4,136 bp (IQR 3,879-4,428) versus 4,167 bp (IQR 3,893-4,501), P = 0.41). Telomere length also did not correlate with any other haematological parameter in both men and women. Conclusions: in contrast to other age-related diseases, telomere length is not associated with anaemia or any other haematological parameter in older individuals in the general population. Show less
