The Paradox of the Adult Stem Cells: Relevance to Aging and Rejuvenation

Adult stem cells (ASCs)Adult stem cells (ASCs) are mostly quiescent but can quickly react and generate differentiated cells upon a tissue injury or disease. ASCs are indispensable in both rejuvenationRejuvenation and agingAging. On the one hand, ASCs are tireless ‘workhorses’ of cellular rejuvenationCellular rejuvenation by replacing worn-out cells with brand-new differentiated cells. On the other hand, ASCs support a tissue cell balance by generating various types of differentiated cells but, paradoxically, cannot save their own tiny population from the age-associated exhaustion. The roots of this ASCs paradox originate from the ambiguity of asymmetric mitosis. In every round of replication, an ASC can generate a group of differentiated cells and a new stem cell but is fundamentally unable to restore its own sporadic losses. Recovery of ASC pool is possible via combination of symmetric and asymmetric replications, as it apparently occurs in development or cancer. We suggest that ASCs in old metazoans either cannot simultaneously afford both modes of replication or, more probably, regulatory systems of higher priority, including antitumor defense, prevent the combined modes of symmetric and asymmetric replications. We posit that intermittent dedifferentiation, spontaneous or artificial, of the only partially differentiated progenitor cells back to multipotent ASCs may induce partial rejuvenationRejuvenation and mitigate negative effects of the ASCs’ depletion in agingAging.