. In this study we analyzed the associations between the distinct cf-DNA species (i.e. unmethylated cf-DNA, mitochondrial DNA, RNAse P gene-coding cf-DNA, Alu repeat cf-DNA and total cf-DNA) and measures of age-associated decline. We also determined the immunological responses associated with cf-DNA levels using genome-wide expression profiling in blood mononuclear cells. The study population consisted of 144 Vitality 90+ Study participants and 30 young controls. In the nonagenarians, higher levels of total and unmethylated cf-DNAs reflected increased systemic inflammation and frailty. Higher mitochondrial DNA copy number was also associated with frailty but not with inflammation. The transcriptomic analysis revealed that elevated levels of total and unmethylated cf-DNAs were associated with immunoinflammatory activation in the nonagenarians but not in the young controls. However, the plasma mitochondrial DNA appeared to be inert in terms of inflammatory activation. These data demonstrate cf-DNA could be used as a biomarker of age-associated decline. In addition, circulating cf-DNA might potentiate immunoinflammatory reactivity in very old individuals.
Jylhävä J, Nevalainen T, Marttila S, Jylhä M, Hervonen A, Hurme M. Aging Cell. 2013 Jun;12(3):388-97. doi: 10.1111/acel.12058.