Aging
Causal effects of body composition on lifespan: Mendelian randomization analysis Zhu Liduzi Jiesisibieke* Zhu Liduzi Jiesisibieke Zhu Liduzi Jiesisibieke C Mary Schooling
Background: Observational studies examining the relation of body composition with lifespan are inconsistent. We conducted a Mendelian Randomization (MR) study to assess effects of key features of body composition on lifespan in men and women.
Methods: We conducted a MR study using inverse variance weighting to investigate the impact of measures of body composition (fat mass, fat-free mass, body fat percentage, waist circumference, appendicular lean mass, and grip strength) on lifespan we also adjusted fat-free mass and appendicular lean mass for potential confounding by fat mass, and assessed mediation by waist circumference. Sensitivity analyses included the weighted median and MR-Egger methods.
Results: In univariable MR, genetically predicted fat mass (per standard deviation higher) decreased men’s lifespan by 2.69 years (95% confidence interval [CI] -3.14 to -2.23) and women’s by 2.48 years (95% CI -3.04 to -1.93), with similar findings for body fat percentage and waist circumference. Appendicular lean mass and grip strength were positively associated with lifespan in men, but not women. In multivariable MR, after adjusting for confounding by fat mas, fat-free mass was also beneficial for men. The effect of BMI on lifespan was largely mediated by waist circumference.
Conclusion: Our study reinforces the benefit of lower fat mass, and less central obesity for both men and women and provides additional evidence highlighting the role of body composition rather than relying solely on BMI, with possibly a greater role of lean or fat-free mass in men. Waist circumference is a key target of intervention for men and women.