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G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity


It is widely recognized that mitochondrial function plays an important role in longevity and healthy aging. Considerable attention has been focused on the extension of longevity by caloric or dietary restriction and mutations that alter this process, and these interventions commonly are associated with shifts in mitochondrial function. While the genetic bases of these effects are the focus of much interest, relatively little effort has been directed at understanding the role that mitochondrial DNA (mtDNA) polymorphisms play in the diet restriction response. This work presents a comprehensive effort to quantify the effects of mtDNA variants, nuclear genetic variants and dietary manipulations on longevity in Drosophila, with a focus on testing for the importance of the interactions among these factors. We found that mitochondrial genotypes can have significant effects on longevity and the diet restriction response but these effects are highly dependent on nuclear genetic (G) background and the specific diet environment (E). For example, a mitochondrial haplotype that shortens lifespan in one nuclear background or diet regime shows no such effect when the genetic background or diet regime is changed. Our experiments indicate that identifying individual mitochondrial, nuclear or dietary effects on longevity is unlikely to provide general results without quantifying the prevalent mitochondrial × nuclear × diet (G×G×E) interactions.


Vyšlo v časopise: G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004354
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004354

Souhrn

It is widely recognized that mitochondrial function plays an important role in longevity and healthy aging. Considerable attention has been focused on the extension of longevity by caloric or dietary restriction and mutations that alter this process, and these interventions commonly are associated with shifts in mitochondrial function. While the genetic bases of these effects are the focus of much interest, relatively little effort has been directed at understanding the role that mitochondrial DNA (mtDNA) polymorphisms play in the diet restriction response. This work presents a comprehensive effort to quantify the effects of mtDNA variants, nuclear genetic variants and dietary manipulations on longevity in Drosophila, with a focus on testing for the importance of the interactions among these factors. We found that mitochondrial genotypes can have significant effects on longevity and the diet restriction response but these effects are highly dependent on nuclear genetic (G) background and the specific diet environment (E). For example, a mitochondrial haplotype that shortens lifespan in one nuclear background or diet regime shows no such effect when the genetic background or diet regime is changed. Our experiments indicate that identifying individual mitochondrial, nuclear or dietary effects on longevity is unlikely to provide general results without quantifying the prevalent mitochondrial × nuclear × diet (G×G×E) interactions.


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