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, Ana M
K1 Partial differential equation; Aging; Telomere; Telomerase activity; Hayflick limit; Follicle
K1 62P10 65L05 65M22
AB A discrete model is proposed for the temporal evolution of a population of cells sorted according to theirtelomeric length. This model assumes that, during cell division, the distribution of the genetic material todaughter cells is asymmetric, i.e. chromosomes of one daughter cell have the same telomere length as themother, 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.
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/70504
UL https://uvadoc.uva.es/handle/10324/70504
LA eng
NO Mathematical Biosciences,  April 2023, Volume 358, 108985
DS UVaDOC
RD 16-oct-2024