UC San Diego

There is an exponential increase in the incidence of disease with age such as cancer, cardiovascular disease, and neurological disorders 1,2. Investigating novel approaches to address aging should be given serious consideration since age is a major common risk factor for chronic diseases. Aging and development of progeny to adults has typically been considered a unidirectional process. However, that notion is no longer clear since terminally differentiated cells can now be reprogrammed to an embryonic-like cell—termed induced pluripotent stem cells (iPSC) 3,4. This suggests that at the cellular level, development is not limited to one direction and can be reversible3,4. Lapasset and colleagues conducted experiments showing improvements in markers of aging when fibroblasts from centenarians were reprogrammed to iPSCs and subsequently re-differentiated into “rejuvenated” fibroblasts 5. This experiment and others suggested that reprogramming rejuvenated the cells 5–8. However, it remains unclear when the “rejuvenation” occurred—during the reprogramming process or when the cell was pluripotent. Here, we show that partial reprogramming rejuvenated cells through several reduced hallmarks of aging. Furthermore, partial reprogramming via short term cyclical induction of Yamanaka factors also extended the lifespan of our animal model. Reprogramming may be useful for understanding the molecular basis of aging and this study is a proof of concept that reprogramming has the potential for therapeutic application.