T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
Open accessAbstract
Inflammaging? Blame T cells!: Mitochondrial dysfunction in various tissues is a prominent characteristic of age-related deterioration, but it is unclear how mitochondrial dysfunction in particular cell types contributes to this process. Desdín-Micó et al. generated mice with T cells that were specifically deficient in a mitochondrial DNA–stabilizing protein. These animals exhibited multiple features associated with aging, including neurological, metabolic, muscular, and cardiovascular impairments. The defective T cells initiated an inflammatory program similar to that observed in older animals, a process called “inflammaging.” Blocking the cytokine tumor necrosis factor–α or administering precursors of the cofactor nicotinamide adenine dinucleotide restored many of these symptoms of senescence. These findings may potentially inform future therapies for age-associated diseases, as well as cachexia and cytokine-release syndrome. Science , this issue p. 1371
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Certain cytokines such as IL-1β and IL-6 have clearly emerged as key to promoting inflammaging.
“Certain cytokines, such as IL-1β and IL-6, have clearly emerged as key to promoting inflammaging.83,229–232”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [83]
The section labeled Abstract (page unavailable) identifies IL-6 as an inflammaging-associated cytokine and reports elevated levels in mice with premature inflammaging. It also links a cytokine storm to systemic senescence, but the passages found do not identify IL-1β or establish that IL-6 itself is a key driver of inflammaging. (LLM, conf=0.86)
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- Authors
- Desdín-Micó, G., Soto-Heredero, G., Aranda, J. F., Oller, J., Carrasco, E., Gabandé-Rodríguez, E., Blanco, E. M., Alfranca, A., Cussó, L., Desco, M., Ibañez, B., Gortazar, A. R., Fernández-Marcos, P., Navarro, M. N., Hernaez, B., Alcamí, A., Baixauli, F., & Mittelbrunn, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.
- Hospital Universitario de la Princesa, Madrid, Spain.
- Spanish National Centre for Cardiovascular Research (ES)
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
- Bone Physiopathology Laboratory, Applied Molecular Medicine Institute (IMMA), Universidad San Pablo-CEU, Madrid, Spain.
- Madrid Institute for Advanced Studies (ES)
- Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain.
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Corresponding author
- Aranda, Juan Francisco
- Oller, Jorge
- Baixauli, Francesc
- ORCID
- Venue
- Science
- Published
- 2020-06-19
- Volume
- 368
- Issue
- 6497
- Pages
- 1371-1376
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7616968
- OpenAlex
- W3027187303
- Cited by
- 572
- References
- 30
- Citations by year
- 2026: 99 · 2025: 108 · 2024: 100 · 2023: 94 · 2022: 76 · 2021: 68 · 2020: 27
- FWCI
- 21.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- European Research Council (ERC-2016-StG 715322-EndoMitTalk)
- Juan de la Cierva
- Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (CP 19/014, PI16/188, PI19/00855)
- Atracción de Talento Investigador Grant (2017-T2/BMD-5766)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- inflammaging, premature senescence, multimorbidity, aging, TNF-α, NAD+, age-related diseases, cachexia, cytokine release syndrome, T cell-specific knockout mice
- MeSH terms
- Multimorbidity, Cytokine Release Syndrome, Animals, DNA-Binding Proteins, Female, Inflammation, Longevity, Male, Mice, Mutant Strains, Mitochondria, NAD, Physical Fitness, T-Lymphocytes, Transcription Factors, Tumor Necrosis Factor-alpha, Gene Deletion, Aging, Premature, Mitochondrial Proteins, Mice
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