Genomics of human longevity

Slagboom, P. Eline; Beekman, Marian; Passtoors, Willemijn M.; Deelen, Joris; Vaarhorst, Anika A. M.; Boer, Judith M.; Akker, Erik B. van den; Heemst, Diana van; Craen, Anton J. M. de; Maier, Andrea B.; Rozing, Maarten P.; Mooijaart, Simon P.; Heijmans, Bastiaan T.; Westendorp, Rudi G. J.

doi:10.1098/rstb.2010.0284

Cited by 69 publications

(56 citation statements)

References 55 publications

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“…The genetic component of the longevity has long been investigated by association studies in unrelated centenarians and younger people from the same population (Bathum et al 1998;Bladbjerg et al 1999;Broer et al 2015;De Benedictis et al 1997;Deelen et al 2014;He et al 2014;Minster et al 2015;Schachter et al 1994;Slagboom et al 2011;Tan et al 2001a;Tan et al 2001b) and correlation studies in twins and families (Herskind et al 1996;Kim et al 2015;McGue et al 1993;Yashin et al 1999). Although the number of genes that could affect the interindividual life span variability was expected to be high, there is only one genetic association, apolipoprotein E (APOE), which has been consistently replicated (Brooks-Wilson 2013).…”

Section: Introductionmentioning

confidence: 99%

Associations between STR autosomal markers and longevity

Bediaga

Aznar

Elcoroaristizabal

et al. 2015

AGE

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Life span is a complex and multifactorial trait, which is shaped by genetic, epigenetic, environmental, and stochastic factors. The possibility that highly hypervariable short tandem repeats (STRs) associated with longevity has been largely explored by comparing the genotypic pools of long lived and younger individuals, but results so far have been contradictory. In view of these contradictory findings, the present study aims to investigate whether HUMTHO1 and HUMCSF1PO STRs, previously associated with longevity, exert a role as a modulator of life expectancy, as well as to assess the extent to which other autosomal STR markers are associated with human longevity in population from northern Spain. To that end, 21 autosomal microsatellite markers have been studied in 304 nonagenarian individuals (more than 90 years old) and 516 younger controls of European descent. Our results do not confirm the association found in previous studies between longevity and THO1 and CSF1PO loci. However, significant association between longevity and autosomal STR markers D12S391, D22S1045, and DS441 was observed. Even more, when we compared allelic frequency distribution of the 21 STR markers between cases and controls, we found that 6 out of the 21 STRs studied showed different allelic frequencies, thus suggesting that the genomic portrait of the human longevity is far complex and probably shaped by a high number of genomic loci.

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Section: Introductionmentioning

confidence: 99%

Associations between STR autosomal markers and longevity

Bediaga

Aznar

Elcoroaristizabal

et al. 2015

AGE

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“…Given that a human organism is a much more complex system than a model organism (Christensen et al 2006), it is evident that genetic effects on the aging process should be mediated via coordinate action of a large number of inter-related processes (Kirkwood 2011). Coordinated function is rather relevant to complex biological (Soltow et al 2010;Slagboom et al 2011) and genetic (Bloss et al 2011) networks than to individual genes.…”

Section: Developmental Process 14mentioning

confidence: 99%

Genomics of human health and aging

Kulminski

Culminskaya

2011

AGE

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Despite notable progress of the candidategene and genome-wide association studies (GWAS), understanding the role of genes contributing to human health and lifespan is still very limited. We use the Framingham Heart Study to elucidate if recognizing the role of evolution and systemic processes in an aging organism could advance such studies. We combine throughput methods of GWAS with more detail methods typical for candidate-gene analyses and show that both lifespan and ages at onset of CVD and cancer can be controlled by the same allelic variants. The risk allele carriers are at highly significant risk of premature death (e.g., RR02.9, p 05.0× 10 −66 ), onset of CVD (e.g., RR01.6, p04.6×10 −17 ), and onset of cancer (e.g., RR01.6, p01.5×10 −6 ). The mechanism mediating the revealed genetic associations is likely associated with biological aging. These aging-related phenotypes are associated with a complex network which includes, in this study, 62 correlated SNPs even so these SNPs can be on non-homologous chromosomes. A striking result is three-fold, highly significant (p03.6×10 −10 ) enrichment of non-synonymous SNPs (N027) in this network compared to the entire qualified set of the studied SNPs. Functional significance of this network is strengthened by involvement of genes for these SNPs in fundamental biological processes related to aging (e.g., response to stimuli, protein degradation, apoptosis) and by connections of these genes with neurological (20 genes) and cardiovascular (nine genes) processes and tumorigenesis (10 genes). These results document challenging role of gene networks in regulating human health and aging and call for broadening focus on genomics of such phenotypes.

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“…There is growing evidence about the specific genetic variants that contribute to inter-individual differences in lifespan (7,8) . For example, those carrying the e4 variant of the APOE gene (rs2075650) die younger (9,10) and have increased risk of some age-related diseases including Alzheimer's disease (AD) (11) .…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Nutrition and ageing: knowledge, gaps and research priorities

Mathers

2013

Proc. Nutr. Soc.

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for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK Over the past two centuries human life expectancy has increased by nearly 50 years. Genetic factors account for about one-third of the variation in life expectancy so that most of the interindividual variation in lifespan is explained by stochastic and environmental factors, including diet. In some model organisms, dietary (energy) restriction is a potent, and highly reproducible, means of increasing lifespan and of reducing the risk of age-related dysfunction although whether this strategy is effective in human subjects is unknown. This is ample evidence that the ageing process is plastic and research demonstrates that ageing is driven by the accumulation of molecular damage, which causes the changes in cell and tissue function that characterise the ageing phenotype. This cellular, tissue and organ damage results in the development of agerelated frailty, disabilities and diseases. There are compelling observational data showing links between eating patterns, e.g. the Mediterranean dietary pattern, and ageing. In contrast, there is little empirical evidence that dietary changes can prolong healthy lifespan and there is even less information about the intervention modalities that can produce such sustainable dietary behaviour changes. In conclusion, current research needs include (1) a better understanding of the causal biological pathways linking diet with the ageing trajectory, (2) the development of lifestyle-based interventions, including dietary changes, which are effective in preventing age-related disease and disability and (3) the development of robust markers of healthy ageing, which can be used as surrogate outcome measures in the development and testing of dietary interventions designed to enhance health and well-being long into old age.

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Genomics of human longevity

Cited by 69 publications

References 55 publications

Associations between STR autosomal markers and longevity

Associations between STR autosomal markers and longevity

Genomics of human health and aging

Nutrition and ageing: knowledge, gaps and research priorities

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