Influence of telomerase activity and initial distribution on human follicular aging: moving from a discrete to a continuum model (Q6157785)

This paper describes two models of granulosa cell dynamics in ovarian follicles. The models focus on telomerase activity and telomere length, which they use as a mechanistic definition of cellular aging. They compare a discrete to a continuous random walk model, where the dependent variable of interest is generational age, defined as telomere length, and the independent variable is time \(t\). In the discrete model, telomere length is an integer; while in the continuous model it lies in a real interval. There are three free parameters in either model: the rate of mitosis \(m\), the rate of cell death \(d\), and the rate of telomerase activity \(r\). Both models belong to the class of drift-diffusion processes or Itô processes. The key result is an exact solution of the age distribution of a population of granulosa cells at a given time. The distribution given by the exact solution assumes that the initial age distribution is exponential. The shape of the initial distribution, when exponential, was also found to determine the rate of aging alongside the other model parameters. This suggests that there may be a substantial degree of individual variation in the rate of follicular aging. It is not clear if this is a clinically realistic feature of the model or not, but would certainly be an interesting hypothesis to probe experimentally. Other distributions are also considered, such as normal distributions. In these cases the shape of the initial distribution can be tentatively related to the woman's age, with some implications for women with premature ovarian failure. This research adds to a wider literature on relationships between human fertility and telomeropathies, and outside of mathematical biology may also be of use to researchers studying fertility treatments.