Cellular Plasticity in ageing – iCELLPLASTICITY

Ageing has long been recognized as a major risk factor for many diseases as it associates with dramatically increased chronic diseases, including cancer, diabetes, and neurodegenerative diseases. An emerging view in the ageing research field suggests that ageing may be the underlying driving force for these disorders. With increased global ageing population, understanding physiological ageing and decoding how ageing enables these changes becomes one of the most urgent biomedical challenges. Recent breakthroughs in nuclear reprogramming have revealed that differentiated cells are strikingly plastic with exciting implications for advances in disease modeling and regenerative medicine. During the last years, I have made relevant contributions to the field of pluripotency reprogramming and its relation to cancer and ageing. In particular, I discovered the important role of the aging-regulated tumor suppressor p16 on reprogramming (Nature 2009) and how the tumor suppressor p27 represses pluripotency through a novel transcriptionally-based mechanism (Cell Stem Cell 2012).
Fundamentally, ageing involves loss of proliferative and regenerative potential, while induced cellular plasticity is associated with a gain in the potential for differentiation and capacity for proliferation. Rapid development in the cellular reprogramming field has offered many exciting opportunities for ageing research, such as creating cellular models to study molecular and cellular ageing in vitro. Previously, we showed that ageing has a negative impact on induced cellular plasticity in vitro (Nature, 2009). However, despite the tremendous interests in the field, it is largely unknown how ageing affects cellular plasticity, and how this could potentially impact the age-dependent decline in regeneration capacity. iCELLPLASTICITY hypothesize that dys-regulation of cellular plasticity could be a common link underlying the impaired regenerative capacity and increased chronic disease with ageing. iCELLPLASTICITY will evaluate the relationship between ageing and somatic cellular plasticity in vivo, identify age-dependent molecular determinants of somatic cell identity and explore the possibility of modulating somatic cellular plasticity to facilitate regeneration.
Last thirty years ageing research discovered that the rate of ageing is susceptive to modification. Manipulation of cellular plasticity via medical intervention to curb ageing processes and improve human health span is one of the most exciting challenges for biomedical research in the coming years. Investigation how cellular plasticity is modulated during physiological ageing will further our understanding on fundamental biological processes such as development and ageing. Moreover, it will provide vital information to guide translational applications. This project will provide novel insights of impaired somatic cellular plasticity in chronic diseases and will lead to breakthroughs in the regenerative medicine field.






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