A Markovian growth dynamics on rooted binary trees evolving according to the Gompertz curve (Q453764): Difference between revisions

The paper is inspired by cellular aging due to telomere shortening in mitosis (cell duplication) and studies a random mechanism able to produce the commonly observed (for instance in tumor growth, animal growth and regeneration) Gompertz curve. The assumption is that the process starts at time \(t=0\) with one founder cell at state (mitotic cycle) \(0\) and, at each mitotic cycle, the telomere shortens until it reaches, at exactly cycle number \(n\), a size that allows no further mitotic events. Each cell in state \(k\) (\(0\leq k\leq n-1\)), i.e.~one that results from exactly \(k\) mitotic events, will, independently from the others, duplicate (being replaced by two cells in state \(k+1\)) after a random time with exponential distribution with parameter \(\lambda_k=\beta (n-k)/n\) (\(\beta>0\)) related to its telomere length. Let \(X_n(k,t)\) be the number of cells at state \(k\) at time \(t\) and consider the Markov chain \(X_n(t)=(X_n(0,t),\dots, X_n(n,t))\), which will eventually stop changing when al cells are at state \(n\). Cell death is not considered. \\ This process can alternatively be seen as a ``growth Markov process taking values on the space of rooted binary trees, similar to the Aldous-Shields'' model [\textit{D. Aldous} and \textit{P. Shields}, Probab. Theory Relat. Fields 79, No. 4, 509--542 (1988; Zbl 0641.60026)]. The root is the founder cell and the cell population at time \(t\), \(Z_n(t)=\sum_{k=0}^n X_n(k,t)\), is formed by the active nodes (nodes with no descendants). The present paper shows that the expected value of \(Z_n(t)\) is \(S_n(t)=\left(1-\frac{e^{-\beta t/n}}{2}\right)^n\).\\ The paper looks at the limiting behaviour of the process for large telomere size, as \(n\rightarrow +\infty\). For that, it rescales the population size and time with \(\mathsf{X}_n(\tau)=2^{-n}Z_n(T_n+n\tau)\), where \(T_n=\frac{n}{\beta}\ln \left(\frac{n}{\ln 4}\right)+\frac{\ln 2}{2\beta}\). The expected value of \(\mathsf{X}_n(\tau)\) is \(W_n(\tau)=S_n(T_n+n\tau)\).\\ It is shown that \(\mathsf{X}_n(\tau)\) converges in distribution to a r.v.~equal to the (Gompertz curve) value \(\exp \left(-(\ln 2) e^{-\beta \tau}\right)\) with probability one and that \(W_n(\tau)\) also converges to the Gompertz curve. Using a theorem in [\textit{J. Jacod} and \textit{A. N. Shiryaev}, Limit theorems for stochastic processes. Berlin etc.: Springer-Verlag (1987; Zbl 0635.60021)], this paper proves a central limit theorem: the martingale \(M_n(\tau)=2^{n/2}\left(\mathsf{X}_n(\tau)-\mathsf{X}_n(0)-\frac{n}{2^n}\sum_{k=0}^{n}\lambda_k\int_{0}^{\tau}X(k,T_n+ns)ds\right)\) converges in distribution to a Brownian motion \(B_{v(\tau)}\), with \(v(\tau)=\exp \left(-(\ln 2) e^{-\beta \tau}\right)-1/2\). Some consequences on the average telomere length are then deduced.