Aubrey de Grey and Alexander Wolf debate whether a single mechanism underlies aging

Aubrey de Grey and Alexander Wolf debate whether a single mechanism underlies aging

On August 5, Aubrey de Grey wrote that aging may involve the accumulation of several types of damage that are only partly connected. In this debate, Alexander Wolf proposes a different candidate: stem cell exhaustion as the single dominant mechanism in mammals.

Wolf is looking for a single root cause. He argues that the similarities in aging, its hallmarks, and its biological pathways across mammalian species point to stem cell exhaustion. Wolf links this process to the characteristic tissue atrophy that occurs with age.

De Grey proposes a different causal chain. In his model, normal metabolism gradually produces several classes of damage. These classes are only partly dependent on one another, so de Grey proposes repairing them in parallel.

“Is there one dominant mechanism, or are there several mechanisms with only moderate interdependence? Other evidence supports the second possibility, which in turn supports repairing the damage,” de Grey writes.

In 2023, the authors of a review of the hallmarks of aging identified twelve interconnected processes, including stem cell exhaustion. Wolf places one of these processes at the root of the causal chain. De Grey distinguishes between hallmarks of late-stage pathology and the accumulated damage that he considers their source.

The causal order determines what should be tested in therapy. Wolf’s model centers on an intervention that changes several hallmarks of aging at once. De Grey’s model calls for measuring the repair of each class of damage separately and combining several interventions.