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Journal Article

LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis

MPS-Authors

Wang,  D.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Hou,  L.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Nakamura,  S.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Su,  M.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Li,  F.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Chen,  W.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Yan,  Y.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Green,  C. D.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Chen,  D.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Zhang,  H.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Antebi,  A.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Han,  J. J.
Max Planck Institute for Biology of Ageing, Max Planck Society;

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Citation

Wang, D., Hou, L., Nakamura, S., Su, M., Li, F., Chen, W., et al. (2017). LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis. Aging Cell, 2017(16(1)), 113-124. doi:10.1111/acel.12539.


Abstract
The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN-28/let-7/AKT/DAF-16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level-a central dogma of the 'evolutionary optimization' of resource allocation that modulates aging.