Rejuvenation in distinct cell populations – What does it mean?

Rejuvenation represents a well organized and tightly regulated cellular process in vitro and in vivo, whereby senescent and/or certain differentiated cells revert specific properties acquired during previous steps of maturation to restore again a younger phenotype. Effects of the microenvironment and cellular mechanisms including asymmetric mitosis or retrodifferentiation can contribute to rejuvenation during a dynamic cellular development in contrast to terminally differentiated cells like unicellular organisms, which appear unable to retrodifferentiate and to rejuvenate. The process of rejuvenation is observed in distinct cell populations and includes a coordinated multistep network of transduction cascades with extracellular signaling and cell-to-cell communication to relay intracellular pathways. This provides a certain tissue homeostasis by a regenerative potential and renewal upon tissue-specific repair requirements in addition to residual stem cells, which can vary among different organs and species to extend their life span. However, dysfunctions within a rejuvenation program may also include the risk of neoplastic growth during such a retrograde development. In contrast to rejuvenation in certain cell types, a life span extension – also termed longevity – does not represent a retrograde development but an overall prolonged function of tissues, organs and/or whole organisms. Thus, rejuvenation of a distinct cell population could contribute to longevity of the corresponding organism but may not necessarily be required since longevity could also be achieved mechanistically by inhibition of the mTOR-mediated signaling pathway or by sufficient supply of anti-oxidative defence compounds, physiologically by nutrient restrictions, genetically by the induction of longevity genes or environmentally by the inhibition of aging.