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Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research

A recent paper by Deelen et al. (2014) in Human Molecular Genetics reports the largest genome-wide association study of human longevity to date. While impressive, there is a remarkable lack of association of genes known to considerably extend lifespan in rodents with human longevity, both in this la...

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Detalles Bibliográficos
Autor principal: de Magalhães, João Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614541/
https://www.ncbi.nlm.nih.gov/pubmed/25486354
http://dx.doi.org/10.4161/15384101.2014.950151
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author de Magalhães, João Pedro
author_facet de Magalhães, João Pedro
author_sort de Magalhães, João Pedro
collection PubMed
description A recent paper by Deelen et al. (2014) in Human Molecular Genetics reports the largest genome-wide association study of human longevity to date. While impressive, there is a remarkable lack of association of genes known to considerably extend lifespan in rodents with human longevity, both in this latest study and in genetic association studies in general. Here, I discuss several possible explanations, such as intrinsic limitations in longevity association studies and the complex genetic architecture of longevity. Yet one hypothesis is that the lack of correlation between longevity-associated genes in model organisms and genes associated with human longevity is, at least partly, due to intrinsic limitations and biases in animal studies. In particular, most studies in model organisms are conducted in strains of limited genetic diversity which are then not applicable to human populations. This has important implications and, together with other recent results demonstrating strain-specific longevity effects in rodents due to caloric restriction, it questions our capacity to translate the exciting findings from the genetics of aging to human therapies.
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spelling pubmed-46145412015-10-30 Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research de Magalhães, João Pedro Cell Cycle Perspectives A recent paper by Deelen et al. (2014) in Human Molecular Genetics reports the largest genome-wide association study of human longevity to date. While impressive, there is a remarkable lack of association of genes known to considerably extend lifespan in rodents with human longevity, both in this latest study and in genetic association studies in general. Here, I discuss several possible explanations, such as intrinsic limitations in longevity association studies and the complex genetic architecture of longevity. Yet one hypothesis is that the lack of correlation between longevity-associated genes in model organisms and genes associated with human longevity is, at least partly, due to intrinsic limitations and biases in animal studies. In particular, most studies in model organisms are conducted in strains of limited genetic diversity which are then not applicable to human populations. This has important implications and, together with other recent results demonstrating strain-specific longevity effects in rodents due to caloric restriction, it questions our capacity to translate the exciting findings from the genetics of aging to human therapies. Taylor & Francis 2014-10-30 /pmc/articles/PMC4614541/ /pubmed/25486354 http://dx.doi.org/10.4161/15384101.2014.950151 Text en © 2014 The Author(s). Taylor & Francis Group, LLC http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Perspectives
de Magalhães, João Pedro
Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title_full Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title_fullStr Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title_full_unstemmed Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title_short Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
title_sort why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research
topic Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614541/
https://www.ncbi.nlm.nih.gov/pubmed/25486354
http://dx.doi.org/10.4161/15384101.2014.950151
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