Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging.

Nuclear deformation, a hallmark frequently observed in senescent cells, is presumed to be associated with the erosion of chromatin organization at the nuclear periphery. However, how such gradual changes in higher-order genome organization impinge on local epigenetic modifications to drive cellular mechanisms of aging has remained enigmatic. Here, through large-scale epigenomic analyses of isogenic young, senescent, and progeroid human mesenchymal progenitor cells (hMPCs), we delineate a hierarchy of integrated structural state changes that manifest as heterochromatin loss in repressive compartments, euchromatin weakening in active compartments, switching in interfacing topological compartments, and increasing epigenetic entropy.

BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.

Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs).

Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor.

Regenerative capacity declines throughout evolution and with age. In this study, we asked whether metabolic programs underlying regenerative capability might be conserved across species, and if so, whether such metabolic drivers might be harnessed to promote tissue repair. To this end, we conducted metabolomic analyses in two vertebrate organ regeneration models: the axolotl limb blastema and antler stem cells.

Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration.

Accumulating evidence indicates an association between the circadian clock and the aging process. However, it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes. Here, we identified a transcription factor-independent role of CLOCK, a core component of the molecular circadian clock machinery, in counteracting human mesenchymal stem cell (hMSC) decay.