The SR model posits a damage x that drives aging. The rate of change of x is production minus removal plus noise. The SR equation, developed by model selection from longitudinal damage data19, is \(\frac{{dx}}{{dt}}=\eta t-\beta \frac{x}{\kappa +x}+\sqrt{2\epsilon }\xi\). The production of damage ηt rises linearly with age. Damage removal \(\beta \frac{x}{\kappa +x}\) saturates at high damage, with a halfway saturation point of κ. Noise is modeled as Gaussian white noise with amplitude ϵ. Death in the model is a first passage process when \(x\) crosses a death threshold Xc. We also allowed for extrinsic mortality mex, a parameter (also called a Makeham term) that describes death probability per unit time from extrinsic causes15,18. The model schematic is in Fig. 1 left panel, and the parameters are summarized in Table 1. The linear rise of damage with age is required in the model to produce the Gompertz law, in which mortality hazard grows exponentially with time exp(αt). If one changes the linear rise \(\eta t\) to, say, a quadratic rise ηt2, one would get h ~ exp(αt2) instead of the Gompertz law. Biologically, the rise of production rate with age may represent the accumulation of damage producing units (DPUs) that...

Initially, we analyzed spatial and temporal mouse brain transcriptome data19 to examine Mcmbp expression patterns. We found that Mcmbp expression peaked at E12 and gradually decreased over the following 48 h of cortical development through E15 (Supplementary Fig. 1a). To...