Fig. 1

Fundamental theory of progressive tissue aging that fits with the phenomena of rapid experimental rejuvenation. Increasing with chronological age, damage to differentiated soma – tissue niches of stem cells blocks regenerative responses through deregulation of cell-niche crosstalks. With worsened regenerations, tissues become more damaged (increase in inflammation and fibrosis) and their secretome changes thereby altering the composition of systemic milieu, affecting tissues at a distance, and further inhibiting the capacity of adult stem cells to maintain and repair the tissues