Raghav Sehgal responded to criticism of TranslAGE: a database of 51 studies compares how biological age measures change after interventions
Raghav Sehgal responded to criticism of TranslAGE: a database of 51 studies compares how biological age measures change after interventions
TranslAGE combined 51 human studies in which blood samples were collected before and after an intervention. The authors applied the same methods to every dataset to calculate 16 epigenetic clocks, algorithms that use chemical marks on DNA to estimate age-related changes.
On August 30, Raghav Sehgal, the first author of TranslAGE, responded to criticism from biogerontologist Matt Kaeberlein. Kaeberlein asks a different question: can a change in such a measure tell us how a drug, diet, or exercise program affects a person?
The response map for 16 clocks compiles blood measurements taken before and after interventions in the same 51 studies. The authors standardized the study data and applied the same panel of clocks to every dataset. This makes it possible to compare changes in the measures across groups, follow-up periods, and interventions.
In his public response, Sehgal states the paper’s question as follows:
“Do these biomarkers respond to interventions in the expected direction, by how much, and how consistently?”
Sehgal describes the path toward a measure suitable for clinical trials in three words: prognostic value → responsiveness → surrogacy. Prognostic value links a measure to future disease, physical function, or mortality. Responsiveness describes how the measure changes after an intervention. Surrogacy would allow that change to be used to infer an outcome that matters to the patient.
In the authors’ paper, responsiveness is described as one step toward establishing a surrogate endpoint. TranslAGE examines this specific step by testing how the measures respond to interventions intended to slow aging. Kaeberlein asks the next question: can a change in a measure be linked to the outcome of a specific intervention in an individual?