Telomere Shortening as a Biological Clock: Computational ‎Modeling in Cellular Aging

Saeidian, Shahriar; Motaharinia, Mona; Khoramirad, Mona

doi:10.30473/eab.2026.76939.2026

Document Type : Article

Authors

¹ Department of Biochemistry, Payame Noor University, Tehran, ‎Iran

² ‎. Department of Biology, Kharazmi ‎University, Tehran, Iran‎

³ Department of Biochemistry, ‎Payame Noor University, ‎Tehran, ‎Iran‎

10.30473/eab.2026.76939.2026

Abstract

Telomeres, located at the ends of chromosomes, play a central role in maintaining genomic stability and regulating cellular aging. Telomere shortening is influenced by multiple factors, including cellular proliferation rate, oxidative stress, and telomerase activity. In this study, computational modeling was employed to analyze telomere shortening dynamics in somatic cells and to investigate the effects of proliferation rate, oxidative stress, and telomerase activity on cellular aging. The proposed model successfully reproduced the general patterns observed in telomere shortening dynamics and showed agreement with the experimentally observed Hayflick limit. Sensitivity analysis indicated a strong effect of initial telomere length on replicative capacity. Model results demonstrated that the telomeric exhaustion index (tcrit) varies significantly across biological conditions. In somatic cells with low proliferation rates, tcrit was estimated at approximately 192, whereas in high-turnover tissues such as skin it was approximately 50, and in low-turnover tissues such as the heart it reached approximately 500. These values are interpreted as relative indicators of telomere-dependent replicative capacity consumption within the model framework and do not directly correspond to the lifespan of a single cell or the organism. In telomerase-deficient somatic cells, oxidative stress increased the telomere shortening rate by up to 15%, reducing tcrit to approximately 180. In contrast, in stem cells, tcrit increased to approximately 300, highlighting the protective role of telomerase in maintaining cellular replicative capacity. Overall, the findings support the concept that telomere shortening functions as a molecular biological clock in cellular aging and are consistent with experimental observations.

Keywords

Main Subjects

Biochemistry

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Experimental animal Biology

Telomere Shortening as a Biological Clock: Computational ‎Modeling in Cellular Aging

References

References

Volume 14, Issue 3 - Serial Number 55
March 2026
Pages 21-36

Telomere Shortening as a Biological Clock: Computational ‎Modeling in Cellular Aging

References

References

Volume 14, Issue 3 - Serial Number 55March 2026Pages 21-36

Volume 14, Issue 3 - Serial Number 55
March 2026
Pages 21-36