Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”

Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as “damage‐associated molecular pattern” (DAMP) agents and cause inflammation. As many elderly people are characterized by a low‐grade, chronic inflammatory status defined “inflamm‐aging,” we evalua...

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Bibliographic Details
Published in:European journal of immunology 2014-05, Vol.44 (5), p.1552-1562
Main Authors: Pinti, Marcello, Cevenini, Elisa, Nasi, Milena, De Biasi, Sara, Salvioli, Stefano, Monti, Daniela, Benatti, Stefania, Gibellini, Lara, Cotichini, Rodolfo, Stazi, Maria Antonietta, Trenti, Tommaso, Franceschi, Claudio, Cossarizza, Andrea
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Aging
Aging - immunology
Aging - metabolism
Child
Child, Preschool
Circulating mtDNA
Cytokines
Cytokines - blood
Cytokines - immunology
Deoxyribonucleic acid
DNA
DNA, Mitochondrial - blood
DNA, Mitochondrial - immunology
Female
Humans
Infant
Inflammation
Inflammation - blood
Inflammation - immunology
Longevity
Male
Middle Aged
Mitochondrial DNA
Survival
Ultranonagenarian siblings
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Summary:Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as “damage‐associated molecular pattern” (DAMP) agents and cause inflammation. As many elderly people are characterized by a low‐grade, chronic inflammatory status defined “inflamm‐aging,” we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty‐one Caucasian subjects were enrolled in the study, including 429 siblings aged 90–104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF‐α, IL‐6, RANTES, and IL‐1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF‐α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low‐grade, chronic inflammation observed in elderly people.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201343921