RT info:eu-repo/semantics/article T1 Mathematical modelling of ageing acceleration of the human follicle due to oxidative stress and other factors A1 Portillo de la Fuente, Ana María A1 Peláez Rodríguez, César K1 Matemáticas, Biología K1 aging, oxidation, telomere, telomerase activity, granulosa cell, follicle K1 1206.12 Ecuaciones Diferenciales Ordinarias K1 2411.16 Fisiología de la Reproducción AB There is a gradual telomere shortening due to the inability of the replication machinery to copy the very ends of chromosomes. Additionally, other factors such as high levels of oxidation (free radicals or reactive oxygen species (ROS)), e.g. due to cumulated stress, inflammation or tobacco smoke, accelerate telomere shortening. In humans, the average telomere length is about 10–15 kb at birth and telomeres shorten at a pace of 70 bp per year. However, when cells are exposed to ROS, telomere attrition happens at a faster pace, generating a wide variety of telomere size distribution in different length percentiles, which are different to what is expected just by age. In this work, the generational age of a cell is associated with its telomere length (TL), from certain maximum to the minimal TL that allows replication. In order to study the accumulation of aged granulosa cells in human follicles, from preantral to preovulatory size, a mathematical model is proposed, regarding different degrees of accelerated telomere shortening, which reflect the action of ROS in addition to the telomere shortening that happens after cell division. In cases of cells with TL shorter than cells with average TL, with low telomerase activity and accelerated telomere shortening, the mathematical model predicts an aged outcome in preovulatory follicles. The model provides a plausible explanation for what has been observed in oocytes from older women, which have been exposed to ROS for a longer period of time and have bad outcomes after in vitro fertilization. PB Oxford University Press SN 1477-8599 YR 2021 FD 2021 LK http://uvadoc.uva.es/handle/10324/46331 UL http://uvadoc.uva.es/handle/10324/46331 LA eng NO Mathematical Medicine and Biology: A Journal of the IMA, 2021;, dqab004, https://doi.org/10.1093/imammb/dqab004 NO Producción Científica DS UVaDOC RD 22-nov-2024