Math. Model. Nat. Phenom.
Volume 12, Number 5, 2017Mathematical models in physiology
|Page(s)||48 - 62|
|Published online||13 October 2017|
Modeling of Immunosenescence and Risk of Death from Respiratory Infections: Evaluation of the Role of Antigenic Load and Population Heterogeneity
Institute of Numerical Mathematics, Gubkina 8, 119991, Moscow, Russia
2 Department of Statistical Sciences, Sapienza University of Rome, Italy
3 Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Italy
4 Biodemography of Aging Research Unit, Duke University, Durham, USA
* Corresponding author. E-mail: email@example.com
It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to describe and investigate the mechanism underlying the age pattern of the mortality rate caused by infectious diseases and to determine the cause-specific hazard rate as a function of immune system characteristics. For these purposes we develop a three-compartment model explaining observed risk-of-death. The model incorporates up-to-date knowledge about cellular mechanisms of aging, disease dynamics, population heterogeneity in resistance to infections, and intrinsic aging rate. The results of modeling show that the age-trajectory of mortality caused by respiratory infections may be explained by the value of antigenic load, frequency of infections and the rate of aging of the stem cell population (i.e. the population of T-lymphocyte progenitor cells). The deceleration of infection-induced mortality at advanced age can be explained by selection of individuals with a slower rate of stem cell aging. Parameter estimates derived from fitting mortality data indicate that infection burden was monotonically decreasing during the twentieth century, and changes in total antigenic load were gender-specific: it experienced periodic fluctuations in males and increased approximately two-fold in females.
Mathematics Subject Classification: 91D20 / 92C42 / 93A30
Key words: immunosenescence / respiratory infections / individual hazard
© EDP Sciences, 2017
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