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Related Experiment Video

Updated: Feb 26, 2026

Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans

Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans

Published on: December 9, 2022

FOXO3 longevity interactome on chromosome 6.

Timothy A Donlon^1,2, Brian J Morris^1,3,4, Randi Chen¹

¹Department of Research, Genetics Laboratory, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Honolulu, Hawaii.

|July 20, 2017

Summary

Genetic variations in FOXO3 are linked to longevity. Specific single nucleotide polymorphisms (SNPs) within FOXO3 may regulate its own expression and neighboring genes, forming an aging hub. These findings offer insights into longevity mechanisms.

Keywords:

FOXO3 fluorescence in situ hybridization gene-gene interactions single nucleotide polymorphisms transcription factor binding

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Area of Science:

Genetics
Genomics
Aging Research

Background:

The gene FOXO3 is associated with longevity across diverse human populations.
Understanding the genetic underpinnings of longevity is crucial for developing interventions for healthy aging.

Purpose of the Study:

To identify and characterize single nucleotide polymorphisms (SNPs) in FOXO3 associated with longevity.
To investigate the regulatory mechanisms and genomic interactions of FOXO3 variants in long-lived individuals.

Main Methods:

DNA sequencing of long-lived individuals to identify FOXO3 SNPs.
Analysis of transcription factor binding sites and chromatin looping (RNA polymerase II).
Chromatin conformation capture (3C) techniques to identify long-range physical contacts (CTCF binding sites).

Main Results:

Identified 41 SNPs in FOXO3 associated with longevity, with 13 potentially altering transcription factor binding.
Discovered that these SNPs interact with the FOXO3 promoter, acting as a cis-regulatory unit.
Found long-range physical contacts between FOXO3 and 46 neighboring genes on chromosome 6q21, forming a conserved chromatin domain.

Conclusions:

FOXO3 variants and their interactions within a specific chromatin domain on chromosome 6 may play a significant role in promoting longevity.
FOXO3 functions not only as a transcription factor but also at the genomic level, regulating neighboring genes through chromatin conformation.
Further research into the FOXO3 interactome could reveal key mechanisms of aging and longevity.