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Grant support

This study was supported by the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI16/02188 and PI19/00855; and PI16/02110 to B.I.), the European Regional Development Fund (ERDF), and the European Commission through H2020-EU.1.1 and European Research Council grant ERC-2016-StG 715322-EndoMitTalk. This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). M.M. is supported by the Miguel Servet Program (CPII 19/00014). G.S.-H. is supported by FPI-UAM, J.O. (FJCI-2017-33855) and E.G.-R. (IJC2018-036850) by Juan de la Cierva, and E.C. by Atraccion de Talento Investigador 2017-T2/BMD-5766 (Comunidad de Madrid and UAM). B.I. was supported by ERC research grant ERC-2018-CoG 819775-MATRIX.

Analysis of institutional authors

De La Nuez Gonzalez, JavierAuthorSoto-Heredero GAuthorAranda JfAuthorOller JAuthorCarrasco EAuthorGabandé-Rodríguez EAuthorAlfranca AAuthorNavarro MnAuthorMittelbrunn MCorresponding Author
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Article

T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

Publicated to:SCIENCE. 368 (6497): 1371-1376 - 2020-06-19 368(6497), DOI: 10.1126/science.aax0860

Authors: Desdin-Mico, Gabriela; Soto-Heredero, Gonzalo; Francisco Aranda, Juan; Oller, Jorge; Carrasco, Elisa; Gabande-Rodriguez, Enrique; Maria Blanco, Eva; Alfranca, Arantzazu; Cusso, Lorena; Desco, Manuel; Ibanez, Borja; Gortazar, Arancha R; Fernandez-Marcos, Pablo; Navarro, Maria N; Hernaez, Bruno; Alcami, Antonio; Baixauli, Francesc; Mittelbrunn, Maria

Affiliations

‎ CEI UAM, Madrid Inst Adv Studies IMDEA Food, Metab Syndrome Grp BIOPROMET, CSIC, Madrid, Spain - Author
‎ Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain - Author
‎ Ctr Invest Biomed Red Salud Mental CIBERSA, Madrid, Spain - Author
‎ Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain - Author
‎ Hosp 12 Octubre imas12, Inst Invest Sanitaria, Madrid, Spain - Author
‎ Hosp Univ Princesa, Madrid, Spain - Author
‎ IIS Fdn Jimenez Diaz, Madrid, Spain - Author
‎ Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain - Author
‎ Max Planck Inst Immunobiol & Epigenet, Dept Immunometab, Freiburg, Germany - Author
‎ Univ Autonoma Madrid UAM, CSIC, Ctr Biol Mol Severo Ochoa CBMSO, Dept Biol Mol, Madrid, Spain - Author
‎ Univ Carlos III Madrid, Dept Bioingn & Ingn Aeroesp, Madrid, Spain - Author
‎ Univ San Pablo CEU, Appl Mol Med Inst IMMA, Bone Physiopathol Lab, Madrid, Spain - Author
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Abstract

The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles the chronic inflammation that is characteristic of aging (inflammaging). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor-a signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.

Keywords
Aging, prematureAnimalsCytokine release syndromeDna-binding proteinsFemaleGene deletionInflammationLongevityMaleMiceMice, mutant strainsMitochondriaMitochondrial proteinsMitochondrial transcription factor aMultimorbidityNadPhysical fitnessT-lymphocytesTranscription factorsTumor necrosis factor-alpha

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal SCIENCE due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 2/72, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

This publication has been distinguished as a “Highly Cited Paper” by the agencies WoS (ESI, Clarivate) and ESI (Clarivate), meaning that it ranks within the top 1% of the most cited articles in its thematic field during the year of its publication. In terms of the observed impact of the contribution, this work is considered one of the most influential worldwide, as it is recognized as highly cited. (source consulted: ESI Nov 14, 2024)

And this is evidenced by the extremely high normalized impacts through some of the main indicators of this type, which, although dynamic over time and dependent on the set of average global citations at the time of calculation, already indicate that they are well above the average in different agencies:

  • Normalization of citations relative to the expected citation rate (ESI) by the Clarivate agency: 13.35 (source consulted: ESI Nov 14, 2024)
  • Weighted Average of Normalized Impact by the Scopus agency: 62 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 49.1 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-13, the following number of citations:

  • WoS: 313
  • Scopus: 341
  • Europe PMC: 232
  • OpenCitations: 336
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 654.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 651 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 293.798.
  • The number of mentions on the social network Facebook: 5 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 399 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Desdín-Micó G) and Last Author (MITTELBRUNN HERRERO, MARIA).

the author responsible for correspondence tasks has been MITTELBRUNN HERRERO, MARIA.