Abstract
BACKGROUND: Longevity is one of the most complex phenotypes, and its genetic basis remains unclear. This study aimed to explore the genetic correlation and potential causal association between gut microbiota and longevity. RESULTS: Linkage disequilibrium score (LDSC) regression analysis and a bi-directional two-sample Mendelian Randomization (MR) analysis were performed to analyze gut microbiota and longevity-related traits. LDSC analysis detected four candidate genetic correlations, including Veillonella (genetic correlation = 0.5578, P = 4.67 × 10(- 2)) and Roseburia (genetic correlation = 0.4491, P = 2.67 × 10(- 2)) for longevity, Collinsella (genetic correlation = 0.3144, P = 4.07 × 10(- 2)) for parental lifespan and Sporobacter (genetic correlation = 0.2092, P = 3.53 × 10(- 2)) for healthspan. Further MR analysis observed suggestive causation between Collinsella and parental longevity (father's age at death) (weighted median: b = 1.79 × 10(- 3), P = 3.52 × 10(- 2)). Reverse MR analysis also detected several causal effects of longevity-related traits on gut microbiota, such as longevity and Sporobacter (IVW: b = 7.02 × 10(- 1), P = 4.21 × 10(- 25)). Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. CONCLUSION: Our study found evidence that gut microbiota is causally associated with longevity, or vice versa, providing novel clues for understanding the roles of gut microbiota in aging development.