Marcello Pinti1,2, Elisa Cevenini3,3,2, Milena Nasi4, Sara De Biasi4, Stefano Salvioli3,3, Daniela Monti5, Stefania Benatti1, Lara Gibellini4, Rodolfo Cotichini6,7, Maria Antonietta Stazi7, Tommaso Trenti8, Claudio Franceschi3,3, Andrea Cossarizza4
1Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
2these authors contributed equally to this work
3Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
4Department of Surgery, Medicine, Dentistry, and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy
5Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
6IFC — Institute of Clinical Physiology, CNR Pisa Italy
7National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy
8Department of Clinical Pathology Nuovo Ospedale Civile Sant’Agostino Estense Baggiovara Modena Italy
Tóm tắt
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.
