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Genetic cartography of longevity in humans and mice: Current landscape and horizons.
Hook, Michael; Roy, Suheeta; Williams, Evan G; Bou Sleiman, Maroun; Mozhui, Khyobeni; Nelson, James F; Lu, Lu; Auwerx, Johan; Williams, Robert W.
Afiliación
  • Hook M; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Roy S; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Williams EG; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093, Switzerland.
  • Bou Sleiman M; Interfaculty Institute of Bioengineering, Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
  • Mozhui K; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Nelson JF; Department of Cellular and Integrative Physiology and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Lu L; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Auwerx J; Interfaculty Institute of Bioengineering, Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
  • Williams RW; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: rwilliams@uthsc.edu.
Biochim Biophys Acta Mol Basis Dis ; 1864(9 Pt A): 2718-2732, 2018 09.
Article en En | MEDLINE | ID: mdl-29410319
Aging is a complex and highly variable process. Heritability of longevity among humans and other species is low, and this finding has given rise to the idea that it may be futile to search for DNA variants that modulate aging. We argue that the problem in mapping longevity genes is mainly one of low power and the genetic and environmental complexity of aging. In this review we highlight progress made in mapping genes and molecular networks associated with longevity, paying special attention to work in mice and humans. We summarize 40 years of linkage studies using murine cohorts and 15 years of studies in human populations that have exploited candidate gene and genome-wide association methods. A small but growing number of gene variants contribute to known longevity mechanisms, but a much larger set have unknown functions. We outline these and other challenges and suggest some possible solutions, including more intense collaboration between research communities that use model organisms and human cohorts. Once hundreds of gene variants have been linked to differences in longevity in mammals, it will become feasible to systematically explore gene-by-environmental interactions, dissect mechanisms with more assurance, and evaluate the roles of epistasis and epigenetics in aging. A deeper understanding of complex networks-genetic, cellular, physiological, and social-should position us well to improve healthspan.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Estudio de Asociación del Genoma Completo / Longevidad Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Estudio de Asociación del Genoma Completo / Longevidad Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos