Gene-Environment interactions and stochastic variations in the Gero-Exposome.

The limited heritability of human lifespans suggests an important role for gene-environment (GxE) interactions across the lifespan (T), from gametes to geronts. Multi-level GxExT 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 lifespans in the same culture environment, and for variegated gene expression of somatic cells in nematodes and mammals. These phenotypic complexities can be analyzed as three-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.

• Publication year

  2021

• Venue

  The journals of gerontology. Series A, Biological sciences and medical sciences

• Publication date

  2021-02-13

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1093/gerona/glab045PMID 33580247PMCID PMC8436990
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Genetics of aging.

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• A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals?

  1990cited by this paper
• The structure of the ventral nerve cord of Caenorhabditis elegans.

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