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González-Bermúdez BAuthorPlaza GrAuthor

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September 1, 2022
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Mitochondrial DNA insertions into nuclear DNA affecting chromosome segregation: Insights for a novel mechanism of immunosenescence in mice

Publicated to:Mechanisms Of Ageing And Development. 207 111722- - 2022-01-01 207(), DOI: 10.1016/j.mad.2022.111722

Authors: González-Sánchez M; García-Martínez V; Bravo S; Kobayashi H; Martínez de Toda I; González-Bermúdez B; Plaza GR; De la Fuente M

Affiliations

Univ Complutense Madrid, Fac Ciencias Biol, Dept Genet Physiol & Microbiol, E-28040 Madrid, Spain - Author
Univ Politecn Madrid, Ctr Biomed Technol, E-28223 Pozuelo De Alarcon, Spain - Author
Univ Politecn Madrid, ETSI Caminos Canales & Puertos, Dept Mat Sci, E-28040 Madrid, Spain - Author

Abstract

Mitochondrial DNA sequences were found inserted in the nuclear genome of mouse peritoneal T lymphocytes that increased progressively with aging. These insertions were preferentially located at the pericentromeric heterochromatin. In the same individuals, binucleated T-cells with micronuclei showed a significantly increased frequency associated with age. Most of them were positive for centromere sequences, reflecting the loss of chromatids or whole chromosomes. The proliferative capacity of T lymphocytes decreased with age as well as the glutathione reductase activity, whereas the oxidized glutathione and malondialdehyde concentrations exhibited a significant increase. These results may point to a common process that provides insights for a new approach to understanding immunosenescence. We propose a novel mechanism in which mitochondrial fragments, originated by the increased oxidative stress status during aging, accumulate inside the nuclear genome of T lymphocytes in a time-dependent way. The primary entrance of mitochondrial fragments at the pericentromeric regions may compromise chromosome segregation, causing genetic loss that leads to micronuclei formation, rendering aneuploid cells with reduced proliferation capacity, one of the hallmark of immunosenescence. Future experiments deciphering the mechanistic basis of this phenomenon are needed.

Keywords

agecancercellscentromerefragmentsgenomeimmunosenescencelife-stylelymphoproliferationmicronucleimicronucleus frequencymtdnaoxidative stressAnimalsChromosome segregationDna, mitochondrialGlutathione disulfideGlutathione reductaseHeterochromatinHigh-resolution organizationImmunosenescenceLymphoproliferationMalondialdehydeMiceMicronucleiMtdnaNumtsOxidative stress

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Mechanisms Of Ageing And Development due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Developmental Biology.

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 2025-07-28:

  • Google Scholar: 1
  • WoS: 1
  • Scopus: 1

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 2025-07-28:

  • 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: 4.
  • 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: 4 (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: 5.3.
  • The number of mentions on the social network X (formerly Twitter): 9 (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.