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Background  The  SIRT1  gene was associated with the lifespan in several organisms through inflammatory and oxidative stress pathways. Long-term air particulate matter (PM) is detrimental to health through the same pathways.    Methods  We used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) to investigate whether there is a gene-environment (G × E) interaction of  SIRT1  and air pollution on mortality in an older cohort in China. Among 7083 participants with a mean age of 81.1 years, we genotyped nine  SIRT1  alleles for each participant and assessed PM 2.5  concentration using 3-year average concentrations around each participant’s residence. We used Cox-proportional hazards models to estimate the independent and joint effects of  SIRT1  polymorphisms and PM 2.5  exposure on all-cause mortality, adjusting for a set of confounders.    Results  There were 2843 deaths over 42,852 person-years. The mortality hazard ratio (HR) and 95% confidence interval (CI) for each 10 μg/m 3  increase in PM 2·5  was 1.08 (1.05–1.11); for  SIRT1 _391 was 0.77 (0.61, 0.98) in the recessive model after adjustment. In stratified analyses, participants carrying two  SIRT1 _391 minor alleles had a significantly higher HR for each 10 μg/m 3  increase in PM 2.5  than those carrying zero minor alleles (1.323 (95% CI: 1.088, 1.610) vs. 1.062 (1.028, 1.096) p for interaction = 0.03). Moreover, the interaction of  SIRT1  and air pollution on mortality is significant among women but not among men. We did not see significant relationships for  SIRT1 _366,  SIRT1 _773, and  SIRT1 _720.    Conclusion  We found a gene-environment interaction of  SIRT1  and air pollution on mortality, future experimental studies are warranted to depict the mechanism observed in this study.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12940-021-00718-x.

Interaction of Sirtuin 1 (SIRT1) candidate longevity gene and particulate matter (PM2.5) on all-cause mortality: a longitudinal cohort study in China