Peter Fedichev proposed testing theories of aging by asking which of two age-related signals an intervention changes
Peter Fedichev proposed testing theories of aging by asking which of two age-related signals an intervention changes
On August 18, physicist Peter Fedichev published an essay on how to test two explanations of aging. He proposes measuring two components separately: an age-related signal that changes coherently and changes that accumulate independently.
On August 10, Fedichev proposed distinguishing between the questions that theories of aging seek to answer. In the new essay, he proposes an experiment addressing one of these questions: researchers should specify in advance which component of age-related change an intervention is expected to alter.
Supporters of the programmed aging model point to the recurring sequence of age-related changes, the characteristic pace of aging in each species, the large effects of individual genes, and the partial reversibility of some traits. Fedichev defines a program as a mechanism in which one can identify a repository for the schedule, a clock, and a channel that transmits instructions to tissues. The coherent movement of markers reveals shared dynamics across the organism, but it does not by itself establish what produces this coordination.
“The premises are valid. The conclusion does not follow from them.”
In his alternative model, damage gradually reduces the organism’s stability. As the system approaches a critical state, many fast processes begin to change coherently. A shared pattern of age-related traits can therefore emerge without central instructions. The two explanations can be distinguished by examining which changes an intervention affects.
In a mouse preprint, Fedichev and Kristina Perevozchikova separated changes in DNA methylation, the chemical marking of DNA that affects gene activity, into two trajectories. The dynamic trajectory increased exponentially, and its associated DNA sites changed coherently. The linear trajectory reflected an overall decline in methylation. In single-cell data, its sites changed largely independently. The authors interpret this trajectory as the accumulation of entropic changes.
In this analysis, calorie restriction slowed the increase in the dynamic trajectory, while no statistically significant effect on the rate of the linear trajectory was detected. In heterochronic parabiosis, which connects the circulatory systems of a young and an old mouse, the dynamic component was lower two months after separation. The linear component changed neither immediately after the procedure nor two months later.
Fedichev’s reasoning is that if developmental signaling pathways that remain active later in life produce independently accumulated changes, suppressing those pathways should also slow the linear trajectory. He therefore proposes specifying the expected component in advance and measuring both components. A biological age index that combines different changes into a single number may conflate reversible, coherent dynamics with accumulated changes.
The testable question is specific: did the intervention change the particular age-related signal on which the theory is based?