Modelling cell lifespan and proliferation: is likelihood to die or to divide independent of age?

被引:27
作者
Dowling, MR
Milutinovic, D
Hodgkin, PD
机构
[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] Univ Queensland, Sch Phys Sci, Brisbane, Qld 4072, Australia
[3] Univ Utrecht, NL-3584 CH Utrecht, Netherlands
关键词
cell lifespan; cell proliferation; lymphocyte half lives; lognormal;
D O I
10.1098/rsif.2005.0069
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In cell lifespan studies the exponential nature of cell survival curves is often interpreted as showing the rate of death is independent of the age of the cells within the population. Here we present an alternative model where cells that die are replaced and the age and lifespan of the population pool is monitored until a, steady state is reached. In our model newly generated individual cells are given a determined lifespan drawn from a number of known distributions including the lognormal, which is frequently found in nature. For lognormal lifespans the analytic steady-state survival curve obtained can be well-fit by a single or double exponential, depending on the mean and standard deviation. Thus, experimental evidence for exponential lifespans of one and/or two populations cannot be taken as definitive evidence for time and age independence of cell survival. A related model for a dividing population in steady state is also developed. We propose that the common adoption of age-independent, constant rates of change in biological modelling may be responsible for significant errors, both of interpretation and of mathematical deduction. We suggest that additional mathematical and experimental methods must be used to resolve the relationship between time and behavioural changes by cells that are predominantly unsynchronized.
引用
收藏
页码:517 / 526
页数:10
相关论文
共 20 条
[1]   Stochastic model of T cell proliferation: A calculus revealing IL-2 regulation of precursor frequencies, cell cycle time, and survival [J].
Deenick, EK ;
Gett, AV ;
Hodgkin, PD .
JOURNAL OF IMMUNOLOGY, 2003, 170 (10) :4963-4972
[2]   The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery [J].
Ernst, B ;
Lee, DS ;
Chang, JM ;
Sprent, J ;
Surh, CD .
IMMUNITY, 1999, 11 (02) :173-181
[3]   REDUCED LIFE-SPAN OF ANERGIC SELF-REACTIVE B-CELLS IN A DOUBLE-TRANSGENIC MODEL [J].
FULCHER, DA ;
BASTEN, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (01) :125-134
[4]   Influences on the lifespan of B cell subpopulations defined by different phenotypes [J].
Fulcher, DA ;
Basten, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (05) :1188-1199
[5]   A cellular calculus for signal integration by T cells [J].
Gett, AV ;
Hodgkin, PD .
NATURE IMMUNOLOGY, 2000, 1 (03) :239-244
[6]  
HAWKINS E, UNPUB GEN CYTON THEO
[7]   Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules [J].
Kirberg, J ;
Berns, A ;
vonBoehmer, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (08) :1269-1275
[8]  
Limpert E, 2001, BIOSCIENCE, V51, P341, DOI 10.1641/0006-3568(2001)051[0341:LNDATS]2.0.CO
[9]  
2
[10]   IN-VIVO ESTIMATES OF DIVISION AND DEATH RATES OF HUMAN T-LYMPHOCYTES [J].
MCLEAN, AR ;
MICHIE, CA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) :3707-3711