Heat Shock Changes the Heterogeneity Distribution in Populations of Caenorhabditis elegans: Does It Tell Us Anything About the Biological Mechanism of Stress Response?

A. I. Yashin, J. W. Cypser, T. E. Johnson, A. I. Michalski, S. I. Boyko, V. N. Novoseltsev
2002 The journals of gerontology. Series A, Biological sciences and medical sciences  
In this paper we analyze survival data of populations of sterilized nematodes, Caenorhabditis elegans , exposed to heat shocks of different duration at the beginning of their adult lives. There are clear hormesis effects after short exposure to heat and clear debilitation effects after long exposure. Intermediate durations result in a mixture of these two effects. In this latter case, the survival curves for the control and experimental populations intersect. We show that observed effects may
more » ... erved effects may be explained by using a model of discrete heterogeneity. According to this model, each population of worms in the experiment is a mixture of subcohorts of frail, normal, and robust individuals; exposure to heat changes the initial proportion of worms in the subcohorts (heterogeneity distribution); and these changes depend on the duration of exposure. In other words, exposure to heat does not influence mortality rates (survival functions) in the subcohorts but does cause individuals to move from one subcohort to another. In a biological interpretation of this finding we hypothesize that, when coping with stress, the organisms of worms use several lines of defense. Switching these lines on and off in response to stress in individual organisms generates the spectrum of observed survival effects at the population level. We discuss possible molecular biological mechanisms of stress response and directions for further research. HE comparison of empirical survival curves obtained in stress experiments with nematode worms Caenorhabditis elegans shows three major effects of varying duration of heat shock on subsequent survival. In the first one, survival in the stress group is higher than that in the control for all ages. This effect often happens as a result of small exposure to heat shock and is called longevity hormesis. The second effect arises as a result of exposure to heat shock of moderate duration. In this case survival functions in the stress group are lower at young and higher at old ages than those in the control group; that is, the survival functions in the stressed and in the control populations intersect. We call this mixed effect incomplete hormesis. The third effect deals with cases in which survival in the stress group is lower than that in the control for all ages. These effects are the results of long exposure to heat shock, and they are referred to as debilitation. Although longevity hormesis has been the subject of many studies (1-3), the mechanism of incomplete hormesis has yet to be described and investigated in detail. To our knowledge there are also no studies that explain how all three effects (hormesis, incomplete hormesis, and debilitation) arise as a result of an increasing stress load. Such studies would provide important insights for better understanding of the mechanisms of individual response to stress and its manifestation at the population level. Molecular biological studies of stress response show that an organism's adaptation to stress includes, among other things, the induction of stress proteins and the activation of antioxidant production mechanisms (4-9). In this paper we develop a model of stress response in a heterogeneous population. We assume discrete heterogeneity in mortality and perform an estimation of model parameters by using survival data in four basic populations of nematode worms exposed to varying durations of heat stress, that is, in the control, hormesis, incomplete hormesis, and debilitation groups. The results of the analysis allow us to hypothesize that adaptation to heat shock at the level of the worm's organism uses a finite number of strategies. For example, in response to stress, the organism may switch on and off a finite number of defense lines. Different exposures to heat shock generate a difference in the proportions of worms with a respective level of defense. This difference is responsible for a variety of survival curves observed in each stress experiment. We discuss the possibility of using the T
doi:10.1093/gerona/57.3.b83 pmid:11867644 fatcat:navgdovu5fhy5dfbyv6ugdsvpa