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 (mtDNACN) 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 mtDNACN 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 mtDNACN 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 mtDNACN 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 mtDNACN 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 mtDNACN at the middle tertile and in sensitivity analyses. We demonstrate super-additive interactions between decreases in leukocyte mtDNACN and inflammation on the mortality risk in older adults, indicating underlying synergism. Increasing mortality is attributed to deaths in older adults, particularly those due to inflammation-related chronic non-communicable diseases. Through unclear mechanisms, aging is thought to elevate the risk of death in the presence of stressors. It is known that the amount of DNA in the mitochondria of white blood cells changes with age. Here, we investigated whether changes in this DNA over time impact the risk of death with inflammation. We conducted a study in which we tracked the amount of this DNA and a marker of inflammation among older adults. We showed that, among participants with a loss of this DNA over time, an increase in inflammation confers the highest risk of all-cause death and death from cardiovascular diseases. Our results suggest aging, signaled by a decrease in mitochondrial DNA in white blood cells with age, may elevate the death risk in the presence of inflammation. Wu et al. conduct a multi-year longitudinal study to examine the associations of within individual changes in leukocyte mitochondrial DNA copy number(mtDNACN) and serum hsCRP with mortality in older adults. They demonstrated super-additive interactions between a decrease in leukocyte mtDNACN and an increase in serum hs-CRP, indicating synergism.
Wu et al. (Mon,) studied this question.