Association of leukocyte mitochondrial DNA copy number and inflammation with mortality among older adults

As the population ages, a rising mortality burden is attributed to deaths in older adults, particularly deaths from inflammation-related chronic non-communicable diseases. The synergism between aging and inflammation remains unclear. Here, we conducted a study to examine whether a decrease in leukocyte mitochondrial DNA copy number (mtDNA_CN) with age modifies the association between inflammation and the mortality risk in older adults.

A total of 3520 adults (mean [SD] age, 67.6 [7.4] years) underwent serial leukocyte mtDNA_CN and serum high-sensitivity C-reactive protein (hs-CRP) measurements and ascertainment of subsequent all-cause and cardiovascular diseases (CVD) deaths. Mortality risks were estimated using Cox proportional hazards models.

Compared to participants with both a sustainedly low serum hs-CRP and change in leukocyte mtDNA_CN at the highest tertile, the adjusted hazard ratios (95% CI) of all-cause and CVD death are 3.20 (2.20-4.66) and 5.77 (2.72-12.21) for those with both increased serum hs-CRP and change in leukocyte mtDNA_CN at the lowest tertile, 1.48 (0.93-2.38) and 1.24 (0.44-3.53) for those with increased serum hs-CRP alone, and 1.29 (0.93-1.81) and 1.44 (0.70-2.97) for those with a change in leukocyte mtDNA_CN at the lowest tertile alone. The relative excess risks due to interaction (95% CI) for all-cause and CVD death are 1.42 (0.19-2.65) and 4.08 (0.21-7.96). Similar results are observed for those with a change in leukocyte mtDNA_CN at the middle tertile and in sensitivity analyses.

We demonstrate super-additive interactions between decreases in leukocyte mtDNA_CN and inflammation on the mortality risk in older adults, indicating underlying synergism.