Michael Levin and co-authors propose a third theory of aging: cells lose their shared goal of maintaining tissue form
Michael Levin and co-authors propose a third theory of aging: cells lose their shared goal of maintaining tissue form
On August 18, Leo Pio-Lopez, Navneet Jawanda, and Michael Levin published a preprint reviewing theories of aging. They group these theories by their proposed primary cause: the accumulation of damage, the late-life effects of evolutionary programs, and the loss of a coordinated goal among cells within a tissue. The third group describes the authors' own theoretical model.
Damage-based theories attribute aging to molecular and cellular defects that repair mechanisms can no longer compensate for. Evolutionary and program-based theories trace aging to the late-life effects of growth and developmental mechanisms established by natural selection. Levin and his co-authors propose that we should also consider how cells maintain the overall structure of a tissue.
By “goal,” the authors mean a feedback process in which cells compare the tissue's current state with its target structure and reduce the difference between them. During development, this process creates the form of the body. In the authors' model, cells may retain their local functions after development is complete while becoming less able to coordinate repair, growth, and cell replacement with the form of the organ.
An individual cell only needs to regulate its own division and metabolism, whereas maintaining an organ's form requires coordinated activity among many cells. The authors suggest that bioelectric patterns, which are distributions of electrical potentials across tissue, could carry this coordinating information. The review also identifies chemical signals and the mechanical properties of tissue as possible mechanisms. The authors hypothesize that if cells become less able to maintain or interpret the shared pattern of signals, the tissue will deviate from its required structure and function.
The authors distinguish this hypothesis from the idea of imperfect cellular memory. Imperfect cellular memory describes the accumulation of incorrect information about how cells should behave. An anatomical goal instead specifies the state against which cells compare the tissue as a whole. The review identifies two possible traces of this process: the breakdown of bioelectric patterns and AGED, in which the activity of genes that arose at different stages of evolution changes differently across tissues.
In a 2025 paper, the authors had already developed an evolutionary computational model in which cells coordinate form at different levels. In this model, aging emerged after the adult form had been reached, without introduced noise or programmed deterioration, while damage and communication failures accelerated the process. The new review turns this line of work into a research program: researchers would measure the preservation of tissue coordination alongside molecular changes and test whether target patterns can be restored.