基因-环境相互作用与老年暴露组学中的随机变异。
Gene-Environment Interactions and Stochastic Variations in the Gero-Exposome.
机构信息
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA.
Dornsife College, University of Southern California, Los Angeles, CA.
出版信息
J Gerontol A Biol Sci Med Sci. 2021 Sep 13;76(10):1740-1747. doi: 10.1093/gerona/glab045.
Abstract
The limited heritability of human life spans suggests an important role for gene-environment (G × E) interactions across the life span (T), from gametes to geronts. Multilevel G × E × T interactions of aging phenotypes are conceptualized in the Gero-Exposome as Exogenous and Endogenous domains. Stochastic variations in the Endogenous domain contribute to the diversity of aging phenotypes, shown for the diversity of inbred Caenorhabditis elegans life spans in the same culture environment, and for variegated gene expression of somatic cells in nematodes and mammals. These phenotypic complexities can be analyzed as 3-way interactions of gene, environment, and stochastic variations, the Tripartite Phenotype of Aging. Single-cell analyses provide tools to explore this broadening frontier of biogerontology.
摘要
人类寿命的有限遗传性表明，在从配子到老年的整个生命周期中，基因-环境（G×E）相互作用起着重要作用。衰老表型的多层次 G×E×T 相互作用在 Gero-Exposome 中被概念化为外源性和内源性领域。内源性领域中的随机变化导致衰老表型的多样性，这在相同培养环境下的同系 Caenorhabditis elegans 寿命多样性以及线虫和哺乳动物体细胞的基因表达多样化中得到了体现。这些表型复杂性可以作为基因、环境和随机变化的三向相互作用进行分析，即衰老的三分体表型。单细胞分析提供了探索这个拓宽的生物老年学前沿的工具。
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