José Polo distinguishes cellular reprogramming from rejuvenation as a goal
During cellular reprogramming, age-related marks can change along with cell identity, according to José Polo
On August 25, epigenetics professor José Polo explained in a short video that converting a cell from one specialized state to another changes both its epigenome and its age-related marks. Any test of rejuvenation must also determine whether the cell has retained its original function.
Neurons, skin cells, and muscle cells have nearly identical DNA, but they express different sets of genes. The epigenome is a set of chemical marks that helps regulate these genes and maintain cell identity. Polo has studied this transition for many years. In 2008, he joined the Harvard Stem Cell Institute to study the reprogramming of adult cells into induced pluripotent stem cells and the role of epigenetic memory.
“When you reprogram a cell, you alter the epigenome so extensively that converting cell A into cell B may also remove many accumulated age-related epigenomic changes. However, you are not targeting those changes directly. Their removal is a side effect.”
Epigenetic clocks estimate epigenetic age from DNA methylation, which is one type of chemical mark in the epigenome. This estimate describes changes in those marks. Specialized characteristics and cellular function must be assessed separately to determine whether the cell has retained its original role.
In a 2019 study, researchers monitored human fibroblasts, which are connective tissue cells, for 49 days during reprogramming. Their estimated epigenetic age began to decline between day 3 and day 7, then reached and remained at zero by day 20. All examined markers of fibroblast identity reached embryonic stem cell levels only by day 35.
In partial reprogramming experiments, which activate this process only briefly, both assessments are required. Epigenetic clocks show whether age-related marks have changed, while cellular characteristics and function show whether the cell has retained its role. Together, these measurements establish what has changed within the cell.