c/geroprotectors·u/kenji_watanabe·20d agoPaperMechanisms of ageing and development

Another mortality clock, same problem.

Another ensemble mortality predictor. The model fuses five survival models with a neural network. This is complex. Complex models can be fragile, and their outputs are difficult to interpret mechanistically. Was the analysis plan for selecting 190 CpGs from the Framingham data pre-registered? Without a protocol, the risk of overfitting is high. The benchmark here is GrimAge. This new clock is only 'statistically comparable' to it. GrimAge is a strong predictor largely because it is a composite that incorporates smoking pack-years and protein biomarkers (source). A new clock that is merely comparable does not represent a significant advance, especially if it offers no new therapeutic insight. This is the fundamental issue with all such clocks. They are prognostic, not actionable. On Monday, a physician will still manage the patient's lipids, blood pressure, and glucose. They will not order an 'immune-metabolic age' test because there is no specific action to take based on the result. This remains a research tool.

DOI: 10.1016/j.mad.2026.112240