ABSTRACT
One of the main topics of this book is the prevention of the aging process and the rational treatment of cancer in the elderly patient. The prevention and treatment of cancer in the elderly requires a detailed understanding of the aging process, which involves a myriad of agents, including (but not limited to) growth factors, protooncogenes, tumor suppressor genes, and specific enzymes involved in the repair of cellular damage.1-9 The complexity of this subject is clearly indicated by the discovery of numerous growth factors, hundreds of oncogenes, and a unique group of tumor suppressor genes in recent decades. Moreover, hundreds of enzymes involved in molecular, cellular, and systemic changes during the lifespan of the organism are influenced by environment and genetics.10 The physiologic decline of an organism and the presence of disease result from molecular degradation of homeostatic systems,10-12 and these systems are controlled by classical hormones and growth factors.13 This decline is a consequence of the suboptimal functioning of systems that have evolved to protect the cells, but that in the process of decay cause further damage (Figure 9.1). For example, the utilization of energy by mitochondria is much more efficient in young people than in the elderly, and creates an opportunity for stochastic damage as the systems age.10 On the other hand, young cells have significant capacity to resist environmental stress such as that produce by viruses, bacteria, and toxic substances.10,14
The key to understanding aging and cancer is to define the molecular events that control cell growth and cell death.1-10,15-21 Key among these targets is the capacity of the cell to correct molecular damage to its genetic material. The deleterious consequences of DNA damage in mammalian systems-including mutation, cancer, lethality, and some aspects of aging-will be examined in this chapter. Most physical and chemical carcinogens interact primarily with DNA, and the aging cell lacks the capacity to correct the damage in time to avoid decline.10 Fortunately, mammalian organisms are diploid, and this provides them with the capacity to buffer and correct genetic damage. Further environmental challenges to cell growth include the development of modified proteins by either direct chemical modification or gene expression.10,11 For example, when proteins degrade and crosslink, somatic mutations accumulate, and the capacity of the cellular machinery to deal with the folding pathways and protein partnerships is exceeded as the organism ages.11,12
The aims of this chapter are fourfold. First, some key concepts in the field of cancer and aging, such as growth factor-induced cell proliferation in malignant and senescent cells, will be elucidated. Second, the complexity of these concepts will be shown, thereby
demonstrating that simplicity and anticipation of findings are not possible in this area of research. Third, a gene product, called MPS-1 (MPS/S27, metallopanstimulin), which is involved in growth factor-induced responses, in carcinogenic ribotoxic responses, and in the aging process, will be reviewed. Moreover, the experimental use of MPS-1 ribosomal protein and heat-resistant extremophilic
proteins in the diagnosis of oncogenic processes will be summarized. Finally, some insight into pharmacologic approaches to the control of metalloproteins involved in carcinogenesis and aging will be presented. None of the findings reviewed here could be anticipated, because of the complexity of the factors involved in the molecular and
cellular systems active in oncogenesis and aging, such as growth factors, oncogenes, tumor suppressor genes, and apoptosis.
