Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis

Area of Science:

• Environmental Epidemiology
• Genetics
• Longevity Research

Background:

• Environmental factors influence human longevity, but causal links are often unclear.
• The exposome concept integrates environmental exposures for comprehensive analysis.
• Mendelian randomization (MR) is employed to investigate causal relationships.

Purpose of the Study:

• To identify specific environmental exposures causally linked to human longevity.
• To utilize the exposome framework and MR to analyze environmental impacts on lifespan.
• To determine factors that increase or decrease the odds of reaching advanced age.

Main Methods:

• Analysis of 4587 environmental exposures from 361,194 UK Biobank participants.
• Assessment of exogenous and endogenous domains of the exposome.
• Examination of longevity outcomes (survival to 90th/99th percentile age) using MR and validation in independent datasets.

Main Results:

• Eight age-related diseases (e.g., coronary atherosclerosis, Alzheimer's, hypertension, type 2 diabetes) causally linked to reduced longevity.
• Low-density lipoprotein cholesterol negatively impacts longevity; high-density lipoprotein cholesterol shows a positive association.
• Greater body fat (especially trunk fat) and sugar consumption are adverse; higher education is beneficial.

Conclusions:

• Confirms causal links between certain age-related diseases and education with longevity.
• Identifies venous thromboembolism management, sugar intake, and body fat control as potential longevity targets.
• Suggests further research into the mechanisms underlying these causal associations.