The quest for genetic determinants of human longevity: challenges and insights
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TLDR
Large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress in human studies of longevity.Abstract:
Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress.read more
Citations
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Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans
Claudio Franceschi,Miriam Capri,Daniela Monti,Sergio Giunta,Fabiola Olivieri,Federica Sevini,Maria Panagiota Panourgia,Laura Invidia,Laura Celani,Maria Scurti,Elisa Cevenini,Gastone Castellani,Stefano Salvioli +12 more
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Biodemography of human ageing.
TL;DR: Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages.
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FOXO3A genotype is strongly associated with human longevity
Bradley J. Willcox,Timothy A. Donlon,Qimei He,Randi Chen,John S. Grove,Katsuhiko Yano,Kamal Masaki,D. Craig Willcox,Beatriz L. Rodriguez,J. David Curb +9 more
TL;DR: Long-lived men presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls, several of these aging phenotypes were associated with FOXO3A genotype.
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Association of FOXO3A variation with human longevity confirmed in German centenarians
Friederike Flachsbart,Amke Caliebe,Rabea Kleindorp,Hélène Blanché,Huberta von Eller-Eberstein,Susanna Nikolaus,Stefan Schreiber,Almut Nebel +7 more
TL;DR: This study investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provided evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age, and confirmed the initial discovery in the Japanese sample.
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Long live FOXO: unraveling the role of FOXO proteins in aging and longevity
TL;DR: The mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals, and compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.
References
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Journal ArticleDOI
Modest implication of interleukin-6 promoter polymorphisms in longevity.
Lene Christiansen,Lise Bathum,Lise Bathum,Karen Andersen-Ranberg,Bernard Jeune,Kaare Christensen +5 more
TL;DR: A modest, but significant, increase in the frequency of interleukin-6 -174GG homozygotes with age is found suggesting that this genotype is advantageous for longevity.
Journal ArticleDOI
Association of mutations in the hemochromatosis gene with shorter life expectancy.
Lise Bathum,Lene Christiansen,Hanne Nybo,Karen Andersen Ranberg,David Gaist,Bernard Jeune,Niels Erik Petersen,James W. Vaupel,Kaare Christensen +8 more
TL;DR: In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy.
Journal ArticleDOI
P53 codon 72 polymorphism and longevity: additional data on centenarians from continental Italy and Sardinia.
Massimiliano Bonafè,Fabiola Olivieri,Daniela Mari,Giovannella Baggio,Rosario Mattace,Maurizio Berardelli,Paolo Sansoni,Giovanna De Benedictis,Maria De Luca,Francesca Marchegiani,Luca Cavallone,Maurizio Cardelli,Simona Giovagnetti,Luigi Ferrucci,Loredana Amadio,Rosamaria Lisa,Maria Giovanna Tucci,Leonarda Troiano,Gabriella Pini,Paola Gueresi,M. Morellini,Sandro Sorbi,Giovanni Passeri,Cristiana Barbi,Silvana Valensin,Daniela Monti,Luca Deiana,Giovanni Mario Pes,Ciriaco Carru,Claudio Franceschi +29 more
TL;DR: Following the reply letter of Sun et al. (in this issue), the hypothesis that polymorphic variants of p53 have an impact on human longevity, by comparing p53 codon 72 allelic and genotypic frequency distributions between young people and centenarians is tested.
Journal ArticleDOI
Longevity and carrying the C282Y mutation for haemochromatosis on the HFE gene: case control study of 492 French centenarians
TL;DR: Genotypes that increase the concentrations of iron for transport and storage may be associated with an increased risk for common diseases, such as cancers and cardiovascular diseases, and for inflammatory and infectious conditions.
Journal ArticleDOI
The allele (A)-110 in the promoter region of the HSP70-1 gene is unfavorable to longevity in women
Katia Altomare,Valentina Greco,Dina Bellizzi,Maurizio Berardelli,Serena Dato,F. Derango,Sabrina Garasto,Giuseppina Rose,Emidio Feraco,Vincenzo Mari,Giuseppe Passarino,Claudio Franceschi,G. De Benedictis +12 more
TL;DR: Investigating whether the gene pool relevant to the (A/C)-110 polymorphism in the promoter region of the HSP70-1 gene changes as the population ages and survival selection occurs showed that the ( A)-110 allele is unfavorable to longevity in females.