Decoding Cellular Memory: Exploring the Consequences of Cell Proliferation Over Time

Maintaining cell identity is crucial for multicellular organisms; yet this “cellular memory” is potentially compromised each time a cell divides. To date, the degree to which sustained proliferation contributes to the accumulation of epigenetic and transcriptional errors over time, and to aging per se, is largely unknown. In DECODEM, I aim to analyse cell divisions uncoupled from chronological time, to gain unique insight into the cellular mechanisms underlying aging.We will investigate the extent to which a cell’s proliferative history determines its biological age. We will focus on the heterogeneous pool of muscle stem cells (MuSCs), to determine i) the links between the maintenance or loss of proliferative ability of individual MuSCs; ii) the accumulation of epigenetic and transcriptional alterations in different proliferative contexts; iii) the impact of replicative histories on the function of individual cells; and iv) the potential for blocking or reversing proliferation-associated alterations.DECODEM has the potential to reveal the fundamental rules that govern the degradation of transcriptional and epigenetic programs over replicative and chronological time. By advancing our understanding of aging and identifying alterations linked to degraded cell identity, this research holds the potential to contribute to regenerative therapies and to open new avenues for treating age-related diseases.