Osteoporosis induced by cellular senescence: A mathematical model.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 03 03 2024
accepted: 03 05 2024
medline: 28 5 2024
pubmed: 28 5 2024
entrez: 28 5 2024
Statut: epublish

Résumé

Osteoporosis is a disease characterized by loss of bone mass, where bones become fragile and more likely to fracture. Bone density begins to decrease at age 50, and a state of osteoporosis is defined by loss of more than 25%. Cellular senescence is a permanent arrest of normal cell cycle, while maintaining cell viability. The number of senescent cells increase with age. Since osteoporosis is an aging disease, it is natural to consider the question to what extend senescent cells induce bone density loss and osteoporosis. In this paper we use a mathematical model to address this question. We determine the percent of bone loss for men and women during age 50 to 100 years, and the results depend on the rate η of net formation of senescent cell, with η = 1 being the average rate. In the case η = 1, the model simulations are in agreement with empirical data. We also consider senolytic drugs, like fisetin and quercetin, that selectively eliminate senescent cells, and assess their efficacy in terms of reducing bone loss. For example, at η = 1, with estrogen hormonal therapy and early treatment with fisetin, bone density loss for women by age 75 is 23.4% (below osteoporosis), while with no treatment with fisetin it is 25.8% (osteoporosis); without even a treatment with estrogen hormonal therapy, bone loss of 25.3% occurs already at age 65.

Identifiants

pubmed: 38805428
doi: 10.1371/journal.pone.0303978
pii: PONE-D-24-08664
doi:

Substances chimiques

Quercetin 9IKM0I5T1E

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0303978

Informations de copyright

Copyright: © 2024 Siewe, Friedman. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Auteurs

Nourridine Siewe (N)

School of Mathematics and Statistics, College of Science, Rochester Institute of Technology, Rochester, New York, United States of America.

Avner Friedman (A)

Department of Mathematics, The Ohio State University, Columbus, Ohio, United States of America.

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Classifications MeSH