Circulating Mitochondrial DNA at the Crossroads of Mitochondrial Dysfunction and Inflammation During Aging and Muscle Wasting Disorders
Open accessAbstract
Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.
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Alterations in mPTP function contribute to the aging-related loss of muscle mass and function.
“Alterations in mPTP function are undoubtedly contributing to the aging-related loss of muscle mass and function, since mPTP opening can trigger several atrophy-regulating pathways.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [18]
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Self-citationGouspillou, G., Bourdel-Marchasson, I., Rouland, R., Calmettes, G., Franconi, J.-M., Deschodt-Arsac, V., & Diolez, P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.004 · Cited by 62 · see citing works
Marzetti, E., Calvani, R., Lorenzi, M., Tanganelli, F., Picca, A., Bossola, M., Menghi, A., Bernabei, R., & Landi, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.04.003 · Cited by 58 · see citing works
Self-citationWu, H., Wei, H., Sehgal, S. A., Liu, L., & Chen, Q. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.030 · Cited by 57 · see citing works
Pastukh, V. M., Gorodnya, O. M., Gillespie, M. N., & Ruchko, M. V. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.011 · Cited by 54 · see citing works
Mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation
Sadatomi, D., Nakashioya, K., Mamiya, S., Honda, S., Kameyama, Y., Yamamura, Y., Tanimura, S., & Takeda, K. (2016) · The Journal of Biochemistry · doi:10.1093/jb/mvw098 · Cited by 51 · see citing works
Mitochondrial DNA nucleoids determine mitochondrial genetics and dysfunction
Gilkerson, R. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.03.016 · Cited by 49 · see citing works
Picca, A., Pesce, V., Fracasso, F., Joseph, A.-M., Leeuwenburgh, C., & Lezza, A. M. S. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.03.004 · Cited by 44 · see citing works
Self-citationHagiwara, K., Ochiya, T., & Kosaka, N. (2013) · Drug Delivery and Translational Research · doi:10.1007/s13346-013-0180-9 · Cited by 44 · see citing works
Maass, D. L., White, J., Sanders, B., et al. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00367.2004 · Cited by 42 · see citing works
Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise
Shockett, P. E., Khanal, J., Sitaula, A., Oglesby, C., Meachum, W. A., Castracane, V. D., & Kraemer, R. R. (2016) · Physiological Reports · doi:10.14814/phy2.12672 · Cited by 37 · see citing works
"Sr stress" in mixed hindlimb muscles of aging Male rats
Russ, D. W., Krause, J., Wills, A., & Arreguin, R. (2012) · Biogerontology · doi:10.1007/s10522-012-9399-y · Cited by 32 · see citing works
Picca, A., Calvani, R., Lorenzi, M., Menghi, A., Galli, M., Vitiello, R., Randisi, F., Bernabei, R., Landi, F., & Marzetti, E. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.06.005 · Cited by 32 · see citing works
Self-citationLi, H., Liu, J., Yao, J. S., et al. (2016) · Immunologic Research · doi:10.1007/s12026-016-8801-2 · Cited by 31 · see citing works
Use of Anti-Cancer Drugs, Mitocans, to Enhance the Immune Responses against Tumors
Hahn, T., Polanczyk, M. J., Borodovsky, A., Ramanathapuram, L. V., Akporiaye, E. T., & Ralph, S. J. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201011314030010 · Cited by 22 · see citing works
Lezza, A. M. S., Fallacara, F. P., Pesce, V., Leeuwenburgh, C., Cantatore, P., & Gadaleta, M. N. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9866-7 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635 · see citing works
Self-citationThe role of mitochondria in aging
Jang, J. Y., Blum, A., Liu, J., & Finkel, T. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120842 · Cited by 358 · see citing works
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158179 · Cited by 268 · see citing works
“Second, mPTP opening can result in mitochondrial DNA release and consequential activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome, which was shown to increase the expression of ubiquitin ligases involved in muscle atrophy [18,19].”
BackgroundGut Dysbiosis and Muscle Aging: Searching for Novel Targets against Sarcopenia
Picca, A., Fanelli, F., Calvani, R., Mulè, G., Pesce, V., Sisto, A., Pantanelli, C., Bernabei, R., Landi, F., & Marzetti, E. (2018) · Mediators of Inflammation · doi:10.1155/2018/7026198 · Cited by 181 · see citing works
Self-citationMoon, J. S., Goeminne, L. J. E., Kim, J. T., Tian, J. W., Kim, S., Nga, H. T., Kang, S. G., Kang, B. E., Byun, J., Lee, Y., et al. (2020) · Aging Cell · doi:10.1111/acel.13195 · Cited by 141 · see citing works
Update on mitochondria and muscle aging: All wrong roads lead to sarcopenia
Picca, A., Calvani, R., Bossola, M., Allocca, E., Menghi, A., Pesce, V., Lezza, A. M. S., Bernabei, R., Landi, F., & Marzetti, E. (2018) · Biological Chemistry · doi:10.1515/hsz-2017-0331 · Cited by 116 · see citing works
Self-citationMarzetti, E., Guerra, F., Calvani, R., Marini, F., Biancolillo, A., Gervasoni, J., Primiano, A., Coelho-Júnior, H. J., Landi, F., Bernabei, R., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564417 · Cited by 45 · see citing works
Picca, A., Triolo, M., Wohlgemuth, S. E., Martenson, M. S., Mankowski, R. T., Anton, S. D., Marzetti, E., Leeuwenburgh, C., & Hood, D. A. (2023) · Cells · doi:10.3390/cells12010183 · Cited by 23 · see citing works
Self-citation
- Authors
- Picca, A., Lezza, A. M. S., Leeuwenburgh, C., Pesce, V., Calvani, R., Bossola, M., Manes-Gravina, E., Landi, F., Bernabei, R., & Marzetti, E.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- University of Bari Aldo Moro (IT)
- University of Florida (US)
- Corresponding author
- Marzetti, Emanuele
- ORCID
- Venue
- Rejuvenation Research
- Publisher
- SAGE Publications
- Published
- 2018-08
- Volume
- 21
- Issue
- 4
- Pages
- 350-359
- ISSN
- 1094-5458 (ISSN-L)
- 1549-1684
- 1557-8577
- PMC
- PMC6103247
- OpenAlex
- W2767746559
- Cited by
- 144
- References
- 110
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 14 · 2023: 17 · 2022: 13 · 2021: 18 · 2020: 30 · 2019: 23 · 2018: 6 · 2014: 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Rejuvenation Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nd)
- Funders
- University of Florida (1 P30 AG028740)
- Università Cattolica del Sacro Cuore (115621, D3.2 2015, D3.2 2013)
- Fondazione Roma
- National Institute on Aging (P30AG028740)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- circulating mitochondrial DNA, mitochondrial dysfunction, mitochondrial quality control, damage-associated molecular patterns, cell-free mitochondrial DNA, aging, muscle atrophy, sarcopenia, cachexia, inflammation, mitophagy, mitochondrial biogenesis, mitochondrial dynamics
- MeSH terms
- Aging, Animals, DNA, Mitochondrial, Humans, Inflammation, Mitochondria, Oxidative Stress, Sarcopenia
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