In an eight-year study of more than 600 community-dwelling older adults, Johns Hopkins Medicine researchers say they have further linked levels of cell-free DNA (DNA fragments resulting from cell death) circulating in the blood to chronic inflammation and frailty. The study is novel and expands on previous work, the investigators say, because it focused on mitochondrial DNA rather than solely genomic DNA, as previously reported in October 2022.
The new findings, published May 23 in Immunity & Ageing, add to evidence that relatively high levels of DNA fragments found in routine blood samples could be accurate and useful biomarkers, or signals, for a wide range of cognitive and physical decline. Analysis also found correlations between such DNA fragments and the presence of other well-known biomarkers for aging, including cytokine proteins, tumor necrosis factors (proteins made by the immune system in response to tumor growth) and proteins made by the liver when inflammation is present.
For the new study, researchers analyzed blood samples drawn in the mid-1990s from 672 community-dwelling men and women with an average age of 80 at the beginning of the study period. The participants were pulled from three cohort studies based at the RUSH Alzheimer’s Disease Center. The study groups are the Religious Orders Study, the Memory and Aging Project and the Minority Aging Research Study.
All participants received yearly physical and cognitive testing at the time of each blood draw. Cognitive tests included memory, perception and physical tests of grip strength, gait, fatigue and motor function. Researchers then compared levels of long and short CCF-mtDNA fragments against four known biomarkers of inflammation: cytokine proteins, two tumor necrosis factors and inflammatory liver proteins.
Results showed close relationships between the four biomarkers and increased amounts of CCF-mtDNA. For example, if a patient’s blood sample had high amounts of one or more of these known biomarkers for inflammation, the sample also contained high amounts of CCF-mtDNA. Also, researchers found that while high amounts of genomic circulating DNA were linked to cognitive and physical decline, high levels of mitochondrial DNA were more strongly linked to physical decline only.
