Influence of telomerase activity and initial distribution on human follicular aging: Moving from a discrete to a continuum model.

Autor: Portillo AM; Instituto de Investigación en Matemáticas de la Universidad de Valladolid, Valladolid, Spain; Departamento de Matemática Aplicada, Escuela de Ingenierías Industriales, Universidad de Valladolid, Pso. Prado de la Magdalena 3-5, Valladolid, 47011, Spain. Electronic address: ana.portillo@uva.es., Varela E; IVI Foundation, The Health Research Institute La Fe (IIS La Fe), Edificio Biopolo. Av. Fernando Abril Martorell, 106 - Torre A, Planta 1, Valencia, 46026, Spain; Rey Juan Carlos University, Edificio Departamental II. Av. de Atenas, s/n, Alcorcón, Madrid, 28922, Spain. Electronic address: MariaElisa.Varela@ivirma.com., García-Velasco JA; IVI Foundation, The Health Research Institute La Fe (IIS La Fe), Edificio Biopolo. Av. Fernando Abril Martorell, 106 - Torre A, Planta 1, Valencia, 46026, Spain; IVIRMA Madrid, Av. del Talgo, 68, Madrid, 28023, Spain; Rey Juan Carlos University, Edificio Departamental II. Av. de Atenas, s/n, Alcorcón, Madrid, 28922, Spain. Electronic address: Juan.Garcia.Velasco@ivirma.com.
Jazyk: angličtina
Zdroj: Mathematical biosciences [Math Biosci] 2023 Apr; Vol. 358, pp. 108985. Date of Electronic Publication: 2023 Feb 22.
DOI: 10.1016/j.mbs.2023.108985
Abstrakt: A discrete model is proposed for the temporal evolution of a population of cells sorted according to their telomeric length. This model assumes that, during cell division, the distribution of the genetic material to daughter cells is asymmetric, i.e. chromosomes of one daughter cell have the same telomere length as the mother, while in the other daughter cell telomeres are shorter. Telomerase activity and cell death are also taken into account. The continuous model is derived from the discrete model by introducing the generational age as a continuous variable in [0,h], being h the Hayflick limit, i.e. the number of times that a cell can divide before reaching the senescent state. A partial differential equation with boundary conditions is obtained. The solution to this equation depends on the initial telomere length distribution. The initial and boundary value problem is solved exactly when the initial distribution is of exponential type. For other types of initial distributions, a numerical solution is proposed. The model is applied to the human follicular growth from preantral to preovulatory follicle as a case study and the aging rate is studied as a function of telomerase activity, the initial distribution and the Hayflick limit. Young, middle and old cell-aged initial normal distributions are considered. In all cases, when telomerase activity decreases, the population ages and the smaller the h value, the higher the aging rate becomes. However, the influence of these two parameters is different depending on the initial distribution. In conclusion, the worst-case scenario corresponds to an aged initial telomere distribution.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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