Review
Genetic and epigenetic regulation of human aging and longevity

https://doi.org/10.1016/j.bbadis.2018.08.039Get rights and content
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Highlights

  • Genome-wide studies have implicated 57 gene loci in lifespan.

  • Epigenomic changes during aging profoundly affect cell function and stress resistance.

  • Dysregulation of transcriptional and chromatin networks is a crucial to aging.

  • Breakdown in chromatin connectivity results in inappropriate gene expression.

  • Epigenetic drift to an entopic middle ground means previously inactive genes “leak”.

Abstract

Here we summarize the latest data on genetic and epigenetic contributions to human aging and longevity. Whereas environmental and lifestyle factors are important at younger ages, the contribution of genetics appears more important in reaching extreme old age. Genome-wide studies have implicated ~57 gene loci in lifespan. Epigenomic changes during aging profoundly affect cellular function and stress resistance. Dysregulation of transcriptional and chromatin networks is likely a crucial component of aging. Large-scale bioinformatic analyses have revealed involvement of numerous interaction networks. As the young well-differentiated cell replicates into eventual senescence there is drift in the highly regulated chromatin marks towards an entropic middle-ground between repressed and active, such that genes that were previously inactive “leak”. There is a breakdown in chromatin connectivity such that topologically associated domains and their insulators weaken, and well-defined blocks of constitutive heterochromatin give way to generalized, senescence-associated heterochromatin, foci. Together, these phenomena contribute to aging.

Keywords

APOE
FOXO3
Genome-wide association studies
Transcription
Epigenetics
Histones
Network analysis
Aging
Longevity

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This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang.