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

Study · animal · Nature communications · 2025 · DOI 10.1038/s41467-025-57794-7 · PMID 40087268

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

In this mouse study, the researchers examined how mitochondrial activity in zygotes affects telomere length in offspring. Exposing zygotes to 20% O2 or rotenone impaired telomere elongation between the 8-cell and blastocyst stage, with shorter telomeres observed in the Inner Cell Mass and persisting after organogenesis. Similar defects, involving elevated mitochondrial ROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. The authors report that telomere elongation during Inner Cell Mass formation is controlled by mitochondrial-nuclear communication at fertilization, and that using mitochondrially-targeted compounds (BGP-15, MitoQ, SS-31, metformin) it was possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.

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.

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