Michael West: Regeneration Is Distinct from Reversing Cellular Aging

Michael West proposed distinguishing tissue repair from cellular replicative capacity

On August 27, West proposed treating two effects of transient OSKM expression separately: the capacity for tissue repair and the remaining number of cell divisions. In his August 28 response, Peter Adams argued that telomere lengthening need not be the sole marker of cellular rejuvenation.

In an August 27 post, West distinguishes two properties of a specialized cell. Replicative capacity is the number of divisions the cell can still undergo. In West’s model, this capacity is linked to suppression of telomerase, the enzyme that maintains telomeres, which protect the ends of chromosomes. He separately describes the capacity for tissue repair, which declines after early development, and calls this transition maturation.

West compares full and partial reprogramming. Full reprogramming returns a cell to pluripotency, a state from which multiple cell types can develop, and West associates this process with telomerase reactivation. Partial reprogramming transiently expresses OSKM, four factors that alter gene activity, while preserving the cell’s specialized identity. According to West, its purpose is to restore tissues to a regenerative state.

“Partial reprogramming can reactivate the regenerative state, but it does not activate telomerase to reverse cellular aging.”

A week earlier, West had discussed a separate issue: whether a brief and safe OSKM regimen would give damaged tissue enough time to recover. The debate over the duration of this regimen shows why West treats tissue repair as a separate outcome. The result also depends on how much time the tissue needs to repair itself.

West calls the tissue repair outcome induced tissue regeneration. In the debate over ZFP42 and TERT, a single marker was already insufficient to determine whether a cell retained its specialized identity. West applies the same problem to the outcome of the regimen by asking which specific measurement should qualify as rejuvenation.

In his August 28 response to West, Peter Adams challenges West’s chosen boundary:

“It is unclear whether telomere lengthening is required for cellular rejuvenation.”

Adams distinguishes cellular aging from cellular senescence, a state in which a cell stops dividing. He considers the concept of cellular aging itself insufficiently defined. The debate therefore concerns which measurable outcome should count as evidence of rejuvenation: tissue repair, cellular replicative capacity, or another marker.