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May 12, 2025
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Article

KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging

Publicated to: Nature Aging. 5 (5): 799-815 - 2025-05-01 5(5), DOI: 10.1038/s43587-025-00855-9

Authors:

Soto-Heredero, G; Gabandé-Rodríguez, E; Carrasco, E; Escrig-Larena, JI; de las Heras, MMG; Delgado-Pulido, S; Francos-Quijorna, I; Blanco, EM; Fernández-Almeida, A; Abia, D; Rodríguez, MJ; Fernández-Díaz, CM; Alvarez-Flores, MB; de Molina, AR; Jung, SS; del Sol, A; Zorita, V; Sánchez-Cabo, F; Torroja, C; Mittelbrunn, M
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Affiliations

Basque Fdn Sci, IKERBASQUE, Bilbao, Spain - Author
CEI UAM CSIC, IMDEA Food Inst, CEI UAMCS, Madrid, Spain - Author
CIC BioGUNE BRTA Basque Res & Technol Alliance, Bizkaia Technol Pk, Derio, Spain - Author
Inst Salud Carlos III, Ctr Nacl Invest Cardiovasc, Madrid, Spain - Author
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, Consejo Super Invest Cient, Madrid, Spain - Author
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, Serv Microscopia Elect, Madrid, Spain - Author
Univ Autonoma Madrid, Fac Ciencias, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain - Author
Univ Autonoma Madrid, Fac Ciencias, Ctr Biol Mol Severo Ochoa, Dept Biol, Madrid, Spain - Author
Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg - Author
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Abstract

Recent studies using single-cell RNA sequencing technology have uncovered several subpopulations of CD4+ T cells that accumulate with aging. These age-associated T cells are emerging as relevant players in the onset of inflammaging and tissue senescence. Here, based on information provided by single-cell RNA sequencing data, we present a flow cytometry panel that allows the identification of age-associated T cell subsets in systematic larger analysis in mice. We use this panel to evaluate at the single-cell level mitochondrial and senescence marks in the different age-associated CD4+ T cell subpopulations. Our analysis identifies a subpopulation of regulatory T (Treg) cells that is characterized by the extracellular expression of the co-inhibitory molecule killer cell lectin-like receptor subfamily G member 1 (KLRG1) and accumulates with aging in humans and mice. KLRG1-expressing Treg cells display senescence features such as mitochondrial alterations, increased expression of cell-cycle regulators and genomic DNA damage. Functionally, KLRG1+ Treg cells show a reduced suppressive activity in vivo accompanied by a pro-inflammatory phenotype.
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Keywords

ActivatioDysfunctionInflammationMetabolismSenescence

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Aging 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, 2025, it was in position 1/73, thus managing to position itself as a Q1 (Primer Cuartil), in the category Geriatrics & Gerontology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-06:

  • WoS: 9
  • Scopus: 10
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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 2026-04-06:

  • 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: 37.
  • 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: 37 (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: 33.
  • The number of mentions on the social network X (formerly Twitter): 50 (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.
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Leadership analysis of institutional authors

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

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 (SOTO HEREDERO, GONZALO) and Last Author (MITTELBRUNN HERRERO, MARIA).

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

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Awards linked to the item

Funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. This study was supported by European Research Council grant ERC-2021-CoG 101044248-LetTBe, and the Y2020/BIO-6350 NutriSION-CM synergy grant from Comunidad de Madrid, Ministerio de Ciencia e Innovacion, Spain (grants PID2022-141169OB-I00 and PID2022-138295OB-I00). GENYAL Clinical Trials Platform of IMDEA Alimentacion led by A. Ramirez de Molina and R. Ramos Ruiz conducted the volunteer recruitment and human clinical trial. Flow cytometry of human samples was conducted by Flow Cytometry Unit, CNIC, being the cytometer part of the grant EQC2018-005009-P funded by MCIN/AEI/10.13039/501100011033 and by 'ERDF A way of making Europe'. G.S.-H. is supported by a FPI-UAM grant (Universidad Autonoma de Madrid). E.G.-R. was funded by a Juan de la Cierva grant (IJC2018-036850-I; Universidad Autonoma de Madrid). M.G. and J.I.E.-L. are supported by FPU grants (FPU19/02576 and FPU20/04066, respectively), both from Ministerio de Ciencia, Innovacion y Universidades (Spain). E.C. is supported by SI4/PJI/2024-00166 from Comunidad de Madrid and UAM (Spain). S.D.-P. was funded by a PIPF grant (PIPF-2022/SAL-GL-25208), from Comunidad de Madrid (Spain). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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