Oral Presentation 2014 International Biophysics Congress

Using pluripotent stem cell to study and treat aging-associated diseases (#120)

Guanghui Liu 1
  1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China

Global population aging has been causing increasing crisis around the world. Hutchinson–Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two human premature aging disorders with features that closely recapitulate the features of human ageing. Mutations in LMNA and WRN genes lead to aberrant splicing product progerin and protein loss in HGPS and WS, respectively. Study on how genetic alteration leads to the cellular and organismal phenotypes of premature aging will provide clues to the molecular mechanisms that underlie physiological ageing and increased our understanding of molecular pathways contributing to healthy aging. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS [1]. Further, using targeted gene correction technology, we successfully corrected the mutated LMNA gene in HGPS-iPSCs [2]. Finally, by using targeted gene “knock-in” technique, we also created WS-specific human embryonic stem cells (hESCs) with WRN mutation as well as Parkinson’s disease (PD)-specific hESCs with LRRK2 mutation [3]. Upon differentiation of these "diseased" human pluripotent stem cells into different somatic cell types, they demonstrated tissue-specific and aging-associated phenotypic defects. Together, these tools offer an unprecedented platform to study the pathogenesis of human aging and aging-related diseases [4].

  1. Liu, G.H., et al. (2011) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472, 221-225
  2. Liu, G.H., et al. (2011) Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell 8, 688-694
  3. Liu, G.H.*, et al. (2012) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491, 603-607
  4. Liu, G.H.*, et al. (2012) iPSC technology to study human aging and aging-related disorders. Curr Opin Cell Biol. 2012; ;24:765-74