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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 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, 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. [ABSTRACT FROM AUTHOR]

The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing Genomics Institute from China), is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians, and statisticians has been set up. The working plan is to: ( a) collect DNA and information on the health status from an unprecedented number of long-lived 90+ sibpairs ( n= 2650) and of younger ethnically matched controls ( n= 2650) from 11 European countries; ( b) perform a genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals); this investigation will be followed by linkage disequilibrium mapping (LD mapping) of the candidate chromosomal regions; ( c) study in cases (i.e., the 2650 probands of the sibpairs) and controls (2650 younger people), genomic regions (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in previous studies as possible candidates to harbor longevity genes; ( d) genotype all recruited subjects for apoE polymorphisms; and ( e) genotype all recruited subjects for inherited as well as epigenetic variability of the mitochondrial DNA (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms, within the framework of centralized databases for phenotypic, genetic, and mtDNA data. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, functional genomics and proteomics, molecular biology, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow ( a) to identify gender-specific genes involved in healthy aging and longevity in women and men stratified for ethnic and geographic origin and apoE genotype; ( b) to perform a longitudinal survival study to assess the impact of the identified genetic loci on 90+ people mortality; and ( c) to develop mathematical and statistical models capable of combining genetic data with demographic characteristics, health status, socioeconomic factors, lifestyle habits. [ABSTRACT FROM AUTHOR]

The article discusses a study which compared the methylation status of elderly acute myeloid leukaemia (AML) patients with healthy older people to determine differences in age- or disease-related changes. The study involved 26 AML patients and 45 healthy individuals who are community-living participants in Belfast, Northern Ireland. The results reportedly revealed that the degree of methylation at diagnosis may predict AML patients' potential to achieve complete remission.