Benetos Athanase, Fritsch Coralie, Horton Emma, Lenotre Lionel, Toupance Simon, Villemonais Denis
Université de Lorraine, Inserm, DCAC, Nancy, F-54000, France.
Université de Lorraine, CHRU-Nancy, Service de Gériatrie, Nancy, F-54000, France.
J Math Biol. 2025 Jun 2;91(1):8. doi: 10.1007/s00285-025-02230-z.
Telomeres are repetitive sequences of nucleotides at the end of chromosomes, whose evolution over time is intrinsically related to biological ageing. In most cells, with each cell division, telomeres shorten due to the so-called end replication problem, which can lead to replicative senescence and a variety of age-related diseases. On the other hand, in certain cells, the presence of the enzyme telomerase can lead to the lengthening of telomeres, which may delay or prevent the onset of such diseases but can also increase the risk of cancer. In this article, we propose a stochastic representation of this biological model, which takes into account multiple chromosomes per cell, the effect of telomerase, different cell types and the dependence of the distribution of telomere length on the dynamics of the process. We study theoretical properties of this model, including its long-term behaviour. In addition, we investigate numerically the impact of the model parameters on biologically relevant quantities, such as the Hayflick limit and the Malthusian parameter of the population of cells.
端粒是染色体末端的核苷酸重复序列,其随时间的演化与生物衰老内在相关。在大多数细胞中,随着每次细胞分裂,由于所谓的末端复制问题,端粒会缩短,这可能导致复制性衰老和多种与年龄相关的疾病。另一方面,在某些细胞中,端粒酶的存在可导致端粒延长,这可能会延迟或预防此类疾病的发生,但也会增加患癌风险。在本文中,我们提出了这个生物模型的一种随机表示,它考虑了每个细胞中的多条染色体、端粒酶的作用、不同的细胞类型以及端粒长度分布对该过程动力学的依赖性。我们研究了这个模型的理论性质,包括其长期行为。此外,我们通过数值方法研究了模型参数对生物学相关量的影响,例如海弗利克极限和细胞群体的马尔萨斯参数。