Mathematical modelling of ageing acceleration of the human follicle due to oxidative stress and other factors.

Autor:	Portillo AM; Instituto de Investigación en Matemáticas de la Universidad de Valladolid (IMUVa), Departamento de Matemática Aplicada, Escuela de Ingenierías Industriales, Universidad de Valladolid, Paseo del Cauce 59, 47011 Valladolid, Spain., Peláez C; Instituto de Investigación en Matemáticas de la Universidad de Valladolid (IMUVa), Departamento de Matemática Aplicada, Escuela de Ingenierías Industriales, Universidad de Valladolid, Paseo del Cauce 59, 47011 Valladolid, Spain.
Jazyk:	angličtina
Zdroj:	Mathematical medicine and biology : a journal of the IMA [Math Med Biol] 2021 Aug 15; Vol. 38 (3), pp. 273-291.
DOI:	10.1093/imammb/dqab004
Abstrakt:	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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu