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
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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.
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