Reduction of DNA Topoisomerase Top2 reprograms the epigenetic landscape and extends health and life span across species

Опубликована: Янв. 22, 2025

DNA topoisomerases are essential molecular machines that manage topology in the cell and play important roles replication transcription. We find knocking down enzyme Topoisomerase Top2 or its mammalian homolog Top2b increases life span of S. cerevisiae , C. elegans mice. reduction also extends health mice alleviates pathologies aging multiple tissues. At cellular/molecular level, attenuates major hallmarks aging, such as cellular senescence, de-regulated nutrient sensing, epigenetic alteration, lysosomal biogenesis. observed significantly changes landscape various mouse tissues toward those young animals, differentially down-regulates genes with active promoter high expression. Our observations suggest confers longevity effect across species via a conserved mechanism, may be used novel therapeutic strategy for countering aging.

Язык: Английский

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Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(5)

Опубликована: Янв. 30, 2025

Aging is a complex process that affects multiple organs, and the discovery of pharmacological approach to ameliorate aging considered Holy Grail medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish identified accelerated mutant named meteor ( met ), harboring mutation Werner syndrome RecQ - like helicase wrn ) gene. Loss leads short lifespan age-related characteristics intestine embryos, such as cellular senescence, genomic instability, epigenetic alteration. Therefore, conducted antiaging drugs using revealed sapanisertib effectively ameliorated most phenotypes mutant. Mechanistically, geroprotective effects may be attributed inhibition mTORC1/2. Furthermore, also attenuated chronological wild-type aged replicative-senescence human foreskin fibroblasts. Taken together, our study introduces unique efficient model for large-scale drug vertebrates suggests potential therapeutic option treating premature promoting healthy aging.

Язык: Английский

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Regulation and function of insulin and insulin-like growth factor receptor signalling

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Язык: Английский

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Biomarkers of aging: functional aspects still trump molecular parameters

npj Aging, Год журнала: 2025, Номер 11(1)

Опубликована: Март 3, 2025

Biomarkers of aging are indispensable for testing interventions. While promising, the recent focus on molecular aspects should not detract from functional parameters which excellent correlation with mortality, and ample clinical human data exist.

Язык: Английский

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From geroscience to precision geromedicine: Understanding and managing aging

Cell, Год журнала: 2025, Номер 188(8), С. 2043 - 2062

Опубликована: Апрель 1, 2025

Язык: Английский

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