Peter Fedichev proposed classifying theories of aging by the three questions they address
Peter Fedichev proposed classifying theories of aging by the three questions they address
On August 10, Peter Fedichev, a physicist and cofounder of the biotechnology company Gero, published an essay responding to Alan Tomusiak's map of aging theories. Tomusiak arranged sixteen theories along two axes. Fedichev proposes starting by asking which question each theory answers.
Tomusiak's map places free radicals, telomere shortening, the Hallmarks of Aging, which list biological processes associated with aging, and evolutionary explanations alongside one another.
“The sixteen items on Alan's map are not sixteen answers to a single question. They answer at least three different questions: why aging exists, what it is, and how it works.”
Evolutionary theories explain why aging persists under natural selection. Phenomenological models describe patterns at the level of the organism. The Gompertz law, for example, describes the approximately exponential increase in the risk of death with age among adult humans. A molecular hypothesis should connect this trajectory to a process occurring within cells.
In physics, a microscopic explanation connects events at the microscopic level to the observable properties of the system as a whole. Fedichev applies this standard to the biology of aging. Under his criterion, a molecular hypothesis should derive mortality curves and age related changes in measurable organismal traits from events within cells. One example of such a connection is already provided by a model of gene network resilience loss that links the age related increase in mortality to the Gompertz law.
“Such a derivation is the price of admission,” he writes.
The minimal model developed by Fedichev and Jan Gruber includes a stress response, accumulated damage, and regulatory noise, meaning random fluctuations that make it harder for the body's systems to maintain a stable state. The abstract of the preprint, which is a paper published before peer review, states that the model reproduces survival curves and methylation dynamics, meaning changes in chemical marks on DNA, across different animal groups. In the essay, Fedichev presents it as an example of the task that future explanations at the cellular level should address.
In his framework, the Hallmarks remain a list of processes associated with aging, while a phenomenological model describes their shared dynamics. With these categories separated, the debate about the “root cause” becomes a testable question: what aging trajectory should the proposed mechanism produce, and how can the connection between the mechanism and that trajectory be measured in an organism?