The Sebastiano Lab

Prevailing views about aging are shaped by the dogma that development and aging are irreversible. This dogma is exemplified by the famous illustration of the Epigenetic Landscape by C.H. Waddington. The Epigenetic Landscape depicts how we grow after fertilization or as we age, the epigenetics of our cells change, and these changes are “cumulative” and additive and cannot be taken back.

While this is true for the most part, recent stem cell and developmental biology research teaches us also that such irreversible mechanisms can be “undone”. How is this possible?

During preimplantation embryonic development and during primordial germ cell specification there is a natural and massive phenomenomn of epigenetic reprogramming that erases the cell identity of the cells and establishes a brand new program. In 2006-2007 Dr. Shinya Yamanaka made a pioneering discovery showing that a similar process of reprogramming can be achievedin differentiated mouse or human cells by overexpressing a handful of transcription factors. Yamanaka's reprogramming process restored the differentiated cells to a pluripotent state, making them once again capable of recapitulating the scope of normal development.
 

Subsequent research over the past decade has led us to the realization that the Epigenetic Landscape is highly malleable and can be remodeled or “reprogrammed” to various distinct fates. Research in the Sebastiano lab applies this new insight to the challenge of understanding and ameliorating aging.