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Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

Author

Listed:
  • Yasmyn E. Winstanley

    (The University of Adelaide)

  • Ryan D. Rose

    (The University of Adelaide
    St. Andrews Hospital)

  • Alexander P. Sobinoff

    (University of Sydney)

  • Linda L. Wu

    (The University of Adelaide)

  • Deepak Adhikari

    (Monash University)

  • Qing-Hua Zhang

    (Monash University)

  • Jadon K. Wells

    (University of Sydney)

  • Lee H. Wong

    (Monash University)

  • Hazel H. Szeto

    (Social Profit Network)

  • Sandra G. Piltz

    (The University of Adelaide
    South Australian Health & Medical Research Institute)

  • Paul Q. Thomas

    (The University of Adelaide
    South Australian Health & Medical Research Institute)

  • Mark A. Febbraio

    (Monash University)

  • John Carroll

    (Monash University)

  • Hilda A. Pickett

    (University of Sydney)

  • Darryl L. Russell

    (The University of Adelaide)

  • Rebecca L. Robker

    (The University of Adelaide
    Monash University)

Abstract

The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.

Suggested Citation

  • Yasmyn E. Winstanley & Ryan D. Rose & Alexander P. Sobinoff & Linda L. Wu & Deepak Adhikari & Qing-Hua Zhang & Jadon K. Wells & Lee H. Wong & Hazel H. Szeto & Sandra G. Piltz & Paul Q. Thomas & Mark A, 2025. "Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57794-7
    DOI: 10.1038/s41467-025-57794-7
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