multiple body systems in ways that appear to accelerate the rates at which those systems age (Bernhard et al., 2007).
To document the role of chance events on aging one must rigorously control both the genetic composition of an organism and its environment. This has been done to a remarkable degree in a species of nematodes, Caenorhabditis elegans (Vanfleteren et al., 1998). The results confirm hundreds of previous studies with a wide range of species, especially those with inbred rodents housed under apparently identical but less well-controlled environments. One observes wide variations in lifespan in all these studies. For the C. elegans experiments the distributions of lifespan fit best with two-parameter or three-parameter logistic models and not with the classical Gompertz model or the Weibull model.
Many mutations have been shown to substantially increase lifespan in C. elegans. It is of interest, however, that the ranges of the lifespan variations among such mutant strains overlap with those of wild type strains (Kirkwood and Finch, 2002). Many of these long-lived mutant strains exhibit enhanced resistance to a variety of stressors, notably heat shock. It was therefore predicted that variable degrees of response to heat shock stress might form a basis, or a partial basis, for individual variations in longevity. An initial set of experiments demonstrated that is indeed the case, at least for a transgenic construct that includes the promoter of a small heat shock gene (Rea et al., 2005). There was a very strong correlation between the response to heat stress and longevity, with good-responding worms living longer. Strikingly, this phenotype was not heritable. The progeny of a worm showing a strong heat stress reaction exhibited the broad distribution of lifespan shown by the starting population. The heat stress reaction was therefore stochastic. The nature of the chance events that determine the reaction remains unknown. They could be related to the intrinsic instability of the transgene, making it important to repeat such experiments utilizing endogenous genes as reporters of the response to heat shock and other stressors. It could be due to epigenetic drifts in gene expression, perhaps involving random changes in gene promoters or in the state of chemical modifications to histone proteins that coat chromosomes. Such changes have indeed been observed in aging human identical twins (Fraga et al., 2005). While those changes have been interpreted as being driven by the environment, one cannot at present rule out random variations unrelated to environmental influences.
Variations in gene expression in genetically identical organisms examined under environmentally identical conditions have also been attributable to intrinsic noise in fundamental molecular processes such as the transcription and translation of genes. Most such observations have been made using