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M.M. is supported by the Miguel Servet Program (CP 19/014, Fundacion de Investigacion del Hospital 12 de Octubre; the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI19/855), 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. G.K. is supported by the Ligue contre le Cancer (equipe labellisee); Agence National de la Recherche (ANR) - Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association 'Ruban Rose'; Canceropole Ile-de-France; Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumiere; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Universite de Paris ANR-18-IDEX-0001.

Analysis of institutional authors

Mittelbrunn, MariaCorresponding Author
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Review

Hallmarks of T cell aging

Publicated to:NATURE IMMUNOLOGY. 22 (6): 687-698 - 2021-05-13 22(6), DOI: 10.1038/s41590-021-00927-z

Authors: Mittelbrunn, Maria; Kroemer, Guido

Affiliations

Chinese Acad Med Sci, Suzhou Inst Syst Med, Suzhou, Peoples R China - Author
Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France - Author
Inst Gustave Roussy, Metabol & Cell Biol Platforms, Villejuif, France - Author
Inst Invest Sanitaria Hosp 12 Octubre imas12, Madrid, Spain - Author
Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden - Author
Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc,Inserm U1138,Inst Un, Paris, France - Author
Univ Autonoma Madrid UAM, Consejo Super Invest Cient CSIC, Ctr Biol Mol Severo Ochoa CBMSO, Madrid, Spain - Author
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Abstract

In this Review, Mittelbrunn and Kroemer propose that ten molecular hallmarks represent the common denominators of T cell aging. The aged adaptive immune system is characterized by progressive dysfunction as well as increased autoimmunity. This decline is responsible for elevated susceptibility to infection and cancer, as well as decreased vaccination efficacy. Recent evidence indicates that CD4(+) T cell-intrinsic alteratins contribute to chronic inflammation and are sufficient to accelerate an organism-wide aging phenotype, supporting the idea that T cell aging plays a major role in body-wide deterioration. In this Review, we propose ten molecular hallmarks to represent common denominators of T cell aging. These hallmarks are grouped into four primary hallmarks (thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, and loss of proteostasis) and four secondary hallmarks (reduction of the TCR repertoire, naive-memory imbalance, T cell senescence, and lack of effector plasticity), and together they explain the manifestation of the two integrative hallmarks (immunodeficiency and inflammaging). A major challenge now is weighing the relative impact of these hallmarks on T cell aging and understanding their interconnections, with the final goal of defining molecular targets for interventions in the aging process.

Keywords
AccumulationAgeAgingAutoimmunityAutophagyCell plasticityCellular senescenceDiseaseDisease susceptibilityEpigenesis, geneticGene expression regulationHomeostasisHumansImmunity, cellularInflammationMicNaiveProteostasisReceptors, antigen, t-cellResponsesSenescenceT-lymphocytesThymic involutionThymus gland

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal NATURE IMMUNOLOGY 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, 2021, it was in position 4/162, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 24.15. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 25.36 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 75.4 (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: 290
  • Scopus: 355
  • Europe PMC: 216
  • OpenCitations: 309
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: 523.
  • 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: 518 (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: 43.24.
  • The number of mentions on the social network X (formerly Twitter): 32 (Altmetric).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: China; France; Sweden.

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 (MITTELBRUNN HERRERO, MARIA) .

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