RT info:eu-repo/semantics/article
T1 Influence of telomerase activity and initial distribution on human follicular aging: Moving from a discrete to a continuum model
A1 Portillo de la Fuente, Ana María
A1 Varela, E.
A1 García Velasco, J.A.
K1 Matemáticas
K1 Telomere
K1 Follicle
K1 Aging
K1 Partial differential equation
K1 Telómero
K1 Folículo
K1 Envejecimiento
K1 Ecuación diferencial parcial
K1 12 Matemáticas
AB 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 , being 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 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.
PB Elsevier
SN 0025-5564
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/58819
UL https://uvadoc.uva.es/handle/10324/58819
LA eng
NO Mathematical BiosciencesVolume 358, 2023, 108985
NO Producción Científica
DS UVaDOC
RD 17-jul-2024