The causal association between plasma caffeine and frailty: A two-sample mendelian randomization study.

Area of Science:

• Gerontology
• Nutritional Epidemiology
• Genetic Epidemiology

Background:

• Frailty is a significant aging-related condition impacting older adults, families, and society.
• Observational studies suggest a link between caffeine consumption and reduced frailty risk.
• The causal relationship between caffeine and frailty requires more robust investigation.

Purpose of the Study:

• To investigate the causal association between plasma caffeine levels and frailty.
• Utilize Mendelian Randomization (MR) analysis for robust causal inference.

Main Methods:

• Selected single nucleotide polymorphisms (SNPs) associated with plasma caffeine as instrumental variables.
• Employed large-scale datasets from UK Biobank and TwinGen meta-analysis (n=175,226 for Frailty Index; n=386,565 for Fried Frailty Score).
• Applied five MR methods, with inverse-variance weighted (IVW) as the primary analysis.

Main Results:

• Genetically predicted higher plasma caffeine showed a significant inverse association with the Frailty Index (FI).
• Genetically predicted higher plasma caffeine also showed a significant inverse association with the Fried Frailty Score (FFS).
• Results were consistent across sensitivity analyses, including leave-one-out methods.

Conclusions:

• Confirmed a causal relationship between plasma caffeine levels and reduced frailty.
• Suggests that increasing plasma caffeine may be a viable strategy for frailty prevention and risk reduction in aging populations.