Conserved biological processes in partial cellular reprogramming: Relevance to aging and rejuvenation
Roberto A. Avelar, Daniel H. Palmer, Anton Kulaga, Georg Fuellen
Abstract
Partial or transient cellular reprogramming is defined by the limited induction of pluripotency factors without full dedifferentiation of cells to a pluripotent state. Comparing in vitro and in vivo mouse studies, and in vitro studies in humans, supported by visualizations of data interconnections, we show consistent patterns in how such reprogramming modulates key biological processes. Generally, partial reprogramming drives dynamic chromatin remodelling, involving histone modifications that regulate accessibility and facilitate pluripotency gene activation while silencing somatic identity. These changes are accompanied by modifications in stress response programs, such as inflammation, autophagy, and cellular senescence, as well as improved mitochondrial activity and dysregulation of extracellular matrix pathways. We also underscore the challenges in evaluating complex processes like aging and cellular senescence, given the variability in biomarkers used across studies. Overall, we highlight biological processes consistently influenced by reprogramming while noting that some effects are context-dependent, varying according to cell type, species, sex, recovery time, and the reprogramming method employed. These insights inform future research and potential therapeutic applications in aging and regenerative medicine. • Partial cellular reprogramming reverses age-related biological changes and partially resets aging clocks without full dedifferentiation to a pluripotent state. • Chromatin remodelling is a conserved outcome, enhancing accessibility and promoting expression of chromatin modifiers. • Stress response pathways are modulated: senescence markers are reduced, and autophagy is enhanced. • Cancer risk remains a significant challenge, necessitating strict temporal control and optimisation of protocols. • Clinical potential includes treating age-associated diseases and enhancing tissue regeneration while addressing safety concerns.