Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch

Yuval Gielchinsky, Neri Laufer, Efi Weitman, Rinat Abramovitch, Zvi Granot, Yehudit Bergman*, Eli Pikarsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Regenerative capacity is progressively lost with age. Here we show that pregnancy markedly improved liver regeneration in aged mice concomitantly with inducing a switch from proliferation-based liver regeneration to a regenerative processmediated by cell growth.We found that the key mediator of this switch was the Akt/mTORC1 pathway; its inhibition blocked hypertrophy, while increasing proliferation. Moreover, pharmacological activation of this pathway sufficed to induce the hypertrophy module, mimicking pregnancy. This treatment dramatically improved hepatic regenerative capacity and survival of old mice. Thus, cell growth-mediated mass reconstitution, which is relatively resistant to the detrimental effects of aging, is employed in a physiological situation and holds potential as a therapeutic strategy for ameliorating age-related functional deterioration.

Original languageAmerican English
Pages (from-to)543-548
Number of pages6
JournalGenes and Development
Volume24
Issue number6
DOIs
StatePublished - 15 Mar 2010

Keywords

  • Aging
  • Hyperplasia
  • Hypertrophy
  • Liver regeneration
  • mTORC1

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