Related Experiment Video
Updated: Jul 15, 2026
07:25
Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans
Published on: December 9, 2022
Liver X receptor alpha associates with human life span
Simon P Mooijaart1, Maris Kuningas, Rudi G J Westendorp
1Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.p.mooijaart@lumc.nl
Summary
Genetic variations in the liver X receptor alpha (LXRalpha) gene are linked to human lifespan. A specific LXRalpha haplotype was associated with reduced mortality, particularly from infectious diseases, in older adults.
Area of Science:
- Genetics
- Molecular Biology
- Gerontology
Background:
- Nuclear hormone receptors regulate crucial biological processes, including aging and diapause in model organisms like C. elegans.
- The nematode DAF-12 receptor shares sequence similarity with human liver X receptor alpha (LXRalpha).
- LXRalpha plays a role in lipid metabolism and immune response in humans.
Purpose of the Study:
- To investigate the association between genetic variations in the LXRalpha gene (NR1H3) and human lifespan.
- To determine if specific LXRalpha haplotypes influence mortality risk in an elderly population.
Main Methods:
- Genotyping of four single nucleotide polymorphisms (SNPs) within the NR1H3 gene in 563 participants of the Leiden 85-Plus Study.
- Haplotype analysis to identify common genetic variants.
- Statistical analysis to assess the association between haplotypes and mortality over a 7-year follow-up period.
- Measurement of plasma apolipoprotein E and triglyceride levels.
Main Results:
- One common LXRalpha haplotype (haplotype 2) was significantly associated with reduced all-cause mortality (HR 0.78, p =.015).
- This reduced mortality was primarily driven by a significant decrease in mortality from infectious diseases (HR 0.31, p =.023).
- Haplotype 2 also correlated with higher plasma apolipoprotein E levels (p =.018) and triglyceride levels (p =.041).
Conclusions:
- Genetic variation in the NR1H3 gene, encoding LXRalpha, is associated with human lifespan.
- Specific LXRalpha haplotypes may influence longevity and disease susceptibility, potentially through effects on lipid metabolism and immune function.
- These findings highlight LXRalpha as a potential target for interventions aimed at promoting healthy aging.
Related Concept Videos
01:24Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
01:30Liver Physiology
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can also...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can also...